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Rovira II, Biragyn A, Brown LL, Galis ZS, Klauzinska M, Kotliarova SE, Simmons JM, Wali A, Xi D, Yarden RI, Riscuta G. Health and aging trajectories: shared and competing risks and resiliencies for chronic diseases associated with aging. A NIH-wide workshop. Front Public Health 2025; 13:1462217. [PMID: 40376061 PMCID: PMC12078139 DOI: 10.3389/fpubh.2025.1462217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 01/15/2025] [Indexed: 05/18/2025] Open
Affiliation(s)
- Ilsa I. Rovira
- Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Arya Biragyn
- Laboratory of Molecular Biology and Immunology (LMBI), Immunoregulation Section, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, United States
| | - LaVerne L. Brown
- Resilience and Health Studies Program, National Institutes of Health (NIH), Office of Dietary Supplements (ODS), Bethesda, MD, United States
| | - Zorina S. Galis
- Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Malgorzata Klauzinska
- Division of Cancer Biology, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Svetlana E. Kotliarova
- Division of Neuroscience, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Janine M. Simmons
- Office of Behavioral and Social Sciences Research (OBSSR), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Anil Wali
- Center to Reduce Cancer Health Disparities, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Dan Xi
- Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Ronit I. Yarden
- Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Gabriela Riscuta
- Division of Cancer Prevention, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, United States
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2
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Kilili H, Padilla-Morales B, Castillo-Morales A, Monzón-Sandoval J, Díaz-Barba K, Cornejo-Paramo P, Vincze O, Giraudeau M, Bush SJ, Li Z, Chen L, Mourkas E, Ancona S, Gonzalez-Voyer A, Cortez D, Gutierrez H, Székely T, Acuña-Alonzo AP, Urrutia AO. Maximum lifespan and brain size in mammals are associated with gene family size expansion related to immune system functions. Sci Rep 2025; 15:15087. [PMID: 40301502 PMCID: PMC12041557 DOI: 10.1038/s41598-025-98786-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Accepted: 04/15/2025] [Indexed: 05/01/2025] Open
Abstract
Mammals exhibit an unusual variation in their maximum lifespan potential, measured as the longest recorded longevity of any individual in a species. Evidence suggests that lifespan increases follow expansion in brain size relative to body mass. Here, we found significant gene family size expansions associated with maximum lifespan potential and relative brain size but not in gestation time, age of sexual maturity, and body mass in 46 mammalian species. Extended lifespan is associated with expanding gene families enriched in immune system functions. Our results suggest an association between gene duplication in immune-related gene families and the evolution of longer lifespans in mammals. These findings explore the genomic features linked with the evolution of lifespan in mammals and its association with life story and morphological traits.
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Affiliation(s)
- Huseyin Kilili
- Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath, BA2 7AY, UK
| | - Benjamin Padilla-Morales
- Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath, BA2 7AY, UK.
| | | | | | - Karina Díaz-Barba
- Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath, BA2 7AY, UK
- Instituto de Ecología, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
- Licenciatura en Ciencias Genómicas, Universidad Nacional Autónoma de México, CP62210, Cuernavaca, Mexico
| | - Paola Cornejo-Paramo
- Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath, BA2 7AY, UK
- Licenciatura en Ciencias Genómicas, Universidad Nacional Autónoma de México, CP62210, Cuernavaca, Mexico
| | - Orsolya Vincze
- Littoral, Environnement et Sociétés (LIENSs), UMR 7266 CNRS-La Rochelle Université, 2 Rue Olympe de Gouges, FR-17000, La Rochelle, France
- Institute of Aquatic Ecology, Centre for Ecological Research, 4026, Debrecen, Hungary
- Evolutionary Ecology Group, Hungarian Department of Biology and Ecology, Babeş-Bolyai University, 400006, Cluj-Napoca, Romania
| | - Mathieu Giraudeau
- Littoral, Environnement et Sociétés (LIENSs), UMR 7266 CNRS-La Rochelle Université, 2 Rue Olympe de Gouges, FR-17000, La Rochelle, France
| | - Stephen J Bush
- School of Automation Science and Engineering, Xi'an Jiaotong University, Xi'an, China
| | - Zhidan Li
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, 610041, Chengdu, China
| | - Lu Chen
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, 610041, Chengdu, China
| | - Evangelos Mourkas
- Zoonosis Science Centre, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Sergio Ancona
- Instituto de Ecología, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
| | | | - Diego Cortez
- Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, CP62210, Cuernavaca, México
| | - Humberto Gutierrez
- Instituto Nacional de Medicina Genomica, 14610, Ciudad de Mexico, Mexico
| | - Tamás Székely
- Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath, BA2 7AY, UK
- Department of Evolutionary Zoology and Human Biology, University of Debrecen, Debrecen, Hungary
| | - Alín P Acuña-Alonzo
- Instituto de Ecología, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico.
| | - Araxi O Urrutia
- Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath, BA2 7AY, UK.
- Instituto de Ecología, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico.
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Alavimanesh S, Nayerain Jazi N, Choubani M, Saeidi F, Afkhami H, Yarahmadi A, Ronaghi H, Khani P, Modarressi MH. Cellular senescence in the tumor with a bone niche microenvironment: friend or foe? Clin Exp Med 2025; 25:44. [PMID: 39849183 PMCID: PMC11759293 DOI: 10.1007/s10238-025-01564-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 01/08/2025] [Indexed: 01/25/2025]
Abstract
Cellular senescence is understood to be a biological process that is defined as irreversible growth arrest and was originally recognized as a tumor-suppressive mechanism that prevents further propagation of damaged cells. More recently, cellular senescence has been shown to have a dual role in prevention and tumor promotion. Senescent cells carry a senescence-associated secretory phenotype (SASP), which is altered by secretory factors including pro-inflammatory cytokines, chemokines, and other proteases, leading to the alteration of the tissue microenvironment. Though senescence would eventually halt the growth of cancerous potential cells, SASP contributes to the tumor environment by promoting inflammation, matrix remodeling, and tumor cell invasion. The paradox of tumor prevention/promotion is particularly relevant to the bone niche tumor microenvironment, where longer-lasting, chronic inflammation promotes tumor formation. Insights into a mechanistic understanding of cellular senescence and SASP provide the basis for targeted therapies, such as senolytics, which aim to eliminate senescent cells, or SASP inhibitors, which would eliminate the tumor-promoting effects of senescence. These therapeutic interventions offer significant clinical implications for treating cancer and healthy aging.
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Affiliation(s)
- Sajad Alavimanesh
- Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Negar Nayerain Jazi
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maedeh Choubani
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzane Saeidi
- Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
| | - Aref Yarahmadi
- Department of Biology, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran
| | - Hossein Ronaghi
- Department of Orthopedic, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Pouria Khani
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
| | - Mohammad Hossein Modarressi
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
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4
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Cai LQ, Li XC, Wang YY, Chen YX, Zhu XY, Zuo ZY, Si-Ma YQ, Lin YN, Li XK, Huang XY. Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse. Inflammation 2024; 47:2173-2195. [PMID: 38653921 PMCID: PMC11607023 DOI: 10.1007/s10753-024-02032-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 03/31/2024] [Accepted: 04/17/2024] [Indexed: 04/25/2024]
Abstract
Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36-40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36-40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.
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Affiliation(s)
- Lu-Qiong Cai
- Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325000, China
| | - Xiu-Chun Li
- Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325000, China
| | - Yang-Yue Wang
- Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325000, China
| | - Yu-Xin Chen
- Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325000, China
| | - Xia-Yan Zhu
- Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325000, China
| | - Zi-Yi Zuo
- Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325000, China
| | - Yi-Qun Si-Ma
- Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325000, China
| | - Yi-Nuo Lin
- Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325000, China
| | - Xiao-Kun Li
- School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou, Zhejiang, 325000, People's Republic of China
| | - Xiao-Ying Huang
- Division of Pulmonary Medicine, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325000, China.
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5
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Govind S, Lang PO, Bürkle A, Moreno-Villanueva M, Franceschi C, Capri M, Bernard J, Weinberger B, Grubeck-Loebenstein B, Fiegl S, Gonos ES, Sikora E, Jansen E, Dollé MET, Grune T, Breusing N, Aspinall R. Detection of HHV-5 HHV-6a HHV-6b and HHV-7 in the urine: potential use as a non-invasive diagnostic tool for immune profiling. Immun Ageing 2024; 21:84. [PMID: 39609853 PMCID: PMC11606101 DOI: 10.1186/s12979-024-00490-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 11/15/2024] [Indexed: 11/30/2024]
Abstract
Decline in immune function with age has been studied extensively, but approaches to immune restoration have been hampered by the lack of simple methods of identifying individuals whose immune system is in decline. Our approach has been to identify individuals whose immune decline has led to a loss of control of common latent viral infections and their consequent reactivation. Viruses excreted in urine were detected and quantified and we believe this approach could provide a 'surrogate marker' for identifying immune compromised individuals. Here we report the detection of human herpes virus (HHV) 5, 6a, 6b and 7 in the urine of healthy individuals over a wide age range and their correlation with T cell receptor excision circle (TREC) data. The results did not show a clear correlation between TREC values and the detection of individual specific viruses or viral load values when measured singly. However, a correlation was found between low TREC values and the detection of several different human herpes viruses in the urine in males. We present evidence suggesting that for males, the detection of three or more different human herpes viruses in the urine could identify individuals with declining immune function as evidenced by their significantly lower TREC levels.
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Affiliation(s)
- Shelia Govind
- Medicines and Healthcare Products Regulatory Agency (MHRA), South Mimms Laboratories, Potters Bar, UK
| | | | - Alexander Bürkle
- Molecular Toxicology Group, Department of Biology, University of Konstanz, Box 628, Konstanz, 78457, Germany
| | - María Moreno-Villanueva
- Molecular Toxicology Group, Department of Biology, University of Konstanz, Box 628, Konstanz, 78457, Germany
- Human Performance Research Centre, Department of Sport Science, University of Konstanz, Box 30, Konstanz, 78457, Germany
| | - Claudio Franceschi
- Institute of Biogerontology, Lobachevsky State University, Nizhny Novgorod, Russia
| | - Miriam Capri
- Department of Medical and Surgical Sciences, University of Bologna-Alma Mater Studiorum, Bologna, Italy
- Alma Mater Research Institute On Global Challenges and Climate Change (Alma Climate), University of Bologna, Bologna, Italy
| | | | - Birgit Weinberger
- Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria
| | | | | | | | - Ewa Sikora
- Polish Academy of Sciences, Warsaw, Poland
| | - Eugène Jansen
- Centre for Health Protection, National Institute for Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, Utrecht, The Netherlands
| | - Martijn E T Dollé
- National Institute for Public Health and the Environment, Utrecht, The Netherlands
| | - Tilman Grune
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, 14558, Germany
| | - Nicolle Breusing
- Department of Applied Nutritional Science/Dietetics, Institute of Nutritional Medicine, University of Hohenheim, 70599, Stuttgart, Germany
| | - Richard Aspinall
- Centre for Intelligent Healthcare, Coventry University, Priory Street, COVENTRY, CV1 5FB, Conventry, UK.
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Singh SK, Parihar S, Jain S, Ho JAA, Vankayala R. Light-responsive functional nanomaterials as pioneering therapeutics: a paradigm shift to combat age-related disorders. J Mater Chem B 2024; 12:8212-8234. [PMID: 39058026 DOI: 10.1039/d4tb00578c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Aging, marked by dysregulated cellular systems, gives rise to a spectrum of age-related disorders, including neurodegeneration, atherosclerosis, immunosenescence, and musculoskeletal issues. These conditions contribute significantly to the global disease burden, posing challenges to health span and economic resources. Current therapeutic approaches, although diverse in mechanism, often fall short in targeting the underlying cellular pathologies. They fail to address the issues compounded by altered pharmacokinetics in the elderly. Nanotechnology emerges as a transformative solution, offering tissue-specific targeted therapies through nanoparticles. Functional nanomaterials (FNMs) respond to internal or external stimuli, with light-responsive nanomaterials gaining prominence. Harnessing the benefits of deep tissue penetration and ease of manipulation particularly in the near-infrared spectrum, light-responsive FNMs present innovative strategies for age-related comorbidities. This review comprehensively summarizes the potential of light-responsive FNM-based approaches for targeting cellular environments in age-related disorders, and also emphasizes the advantages over traditional treatment modalities. Specifically, it focuses on the development of various classes of light-responsive functional nanomaterials including plasmonic nanomaterials, nanomaterials as carriers, upconversion nanomaterials, 2D nanomaterials, transition metal oxide and dichalcogenide nanomaterials and carbon-based nanomaterials against age related diseases. We foresee that such advanced developments in the field of nanotechnology could provide a new hope for clinical diagnosis and treatment of age-related disorders.
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Affiliation(s)
- Shubham Kumar Singh
- Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Karwar 342030, India.
| | - Shivay Parihar
- Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Karwar 342030, India.
| | - Sanskar Jain
- Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Karwar 342030, India.
| | - Ja-An Annie Ho
- Bioanalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan
- Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan
- Center for Emerging Materials and Advanced Devices, National Taiwan University, Taipei 10617, Taiwan
- Center for Biotechnology, National Taiwan University, Taipei 10617, Taiwan
| | - Raviraj Vankayala
- Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Karwar 342030, India.
- Interdisciplinary Research Platform, Smart Healthcare, Indian Institute of Technology Jodhpur, Karwar 342030, India
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Larbi A. From Genesis to Old Age: Exploring the Immune System One Cell at a Time with Flow Cytometry. Biomedicines 2024; 12:1469. [PMID: 39062042 PMCID: PMC11275137 DOI: 10.3390/biomedicines12071469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 06/21/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
The immune system is a highly complex and tightly regulated system that plays a crucial role in protecting the body against external threats, such as pathogens, and internal abnormalities, like cancer cells. It undergoes development during fetal stages and continuously learns from each encounter with pathogens, allowing it to develop immunological memory and provide a wide range of immune protection. Over time, after numerous encounters and years of functioning, the immune system can begin to show signs of erosion, which is commonly named immunosenescence. In this review, we aim to explore how the immune system responds to initial encounters with antigens and how it handles persistent stimulations throughout a person's lifetime. Our understanding of the immune system has greatly benefited from advanced technologies like flow cytometry. In this context, we will discuss the valuable contribution of flow cytometry in enhancing our knowledge of the immune system behavior in aging, with a specific focus on T-cells. Moreover, we will expand our discussion to the flow cytometry-based assessment of extracellular vesicles, a recently discovered communication channel in biology, and their implications for immune system functioning.
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Affiliation(s)
- Anis Larbi
- Medical and Scientific Affairs, Beckman Coulter Life Sciences, 22 Avenue des Nations, 93420 Villepinte, France;
- Department of Medicine, Division of Geriatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada
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Guo Y, Qian H, Xin X, Liu Q. Effects of different exercise modalities on inflammatory markers in the obese and overweight populations: unraveling the mystery of exercise and inflammation. Front Physiol 2024; 15:1405094. [PMID: 38933362 PMCID: PMC11199780 DOI: 10.3389/fphys.2024.1405094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 05/28/2024] [Indexed: 06/28/2024] Open
Abstract
In the realm of obesity and overweight, the risk of chronic diseases significantly escalates, closely intertwined with inflammatory factors. Research suggests that specific exercise interventions, particularly aerobic exercise and resistance exercise, can have beneficial effects on inflammation levels. However, debates persist regarding the actual impact of exercise in the obese and overweight population. We employed meta-analysis research methods and searched the China National Knowledge Infrastructure Wanfang Data, PubMed, and Web of Science databases to gather controlled experiments on the effects of resistance exercise or aerobic exercise on C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Two researchers independently conducted literature screening and data extraction. The quality of the literature was assessed according to the Cochrane Handbook standards, and subgroup analyses of CRP, IL-6, and TNF-α were performed using RevMan 5.4 software. Through quantitative synthesis of results from 22 selected studies encompassing a total of 1,135 research subjects, this study systematically explored the specific regulatory effects of different exercise modalities on inflammatory markers in the obese and overweight population. The findings indicate that both aerobic exercise and resistance exercise effectively reduce CRP levels in obese individuals, with aerobic exercise demonstrating a more pronounced effect. Aerobic exercise also significantly lowers IL-6 levels, while the impact of resistance exercise on IL-6 is relatively minor. However, in terms of reducing TNF-α levels, neither modality appears to exert a significant effect. Overall, exercise, especially aerobic exercise, emerges as a positive regulator of inflammatory markers in the context of obesity and overweight.
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Affiliation(s)
- Yongqing Guo
- Capital University of Physical Education and Sports, Beijing, China
| | - Haonan Qian
- Department of Physical Education, Hanyang University, Seoul, Republic of Korea
| | - Xianyang Xin
- Capital University of Physical Education and Sports, Beijing, China
| | - Qinlong Liu
- Capital University of Physical Education and Sports, Beijing, China
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Luo C, Zhang Y, Zhang J, Jin C, Ye X, Ren Y, Shen H, Chen M, Li Y, He Q, Xu G, Shao L. Development and validation of a nomogram for predicting pulmonary infection in patients receiving immunosuppressive drugs. Front Pharmacol 2024; 14:1255609. [PMID: 38293665 PMCID: PMC10825965 DOI: 10.3389/fphar.2023.1255609] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 12/31/2023] [Indexed: 02/01/2024] Open
Abstract
Objective: Pulmonary infection (PI), a severe complication of immunosuppressive therapy, affects patients' prognosis. As part of this study, we aimed to construct a pulmonary infection prediction (PIP) model and validate it in patients receiving immunosuppressive drugs (ISDs). Methods: Totally, 7,977 patients being treated with ISDs were randomised 7:3 to the developing (n = 5,583) versus validation datasets (n = 2,394). Our predictive nomogram was established using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. With the use of the concordance index (C-index) and calibration curve, the prediction performance of the final model was evaluated. Results: Among the patients taking immunosuppressive medication, PI was observed in 548 (6.9%). The median time of PI occurrence after immunosuppressive therapy was 123.0 (interquartile range: 63.0, 436.0) days. Thirteen statistically significant independent predictors (sex, age, hypertension, DM, malignant tumour, use of biologics, use of CNIs, use of methylprednisolone at 500 mg, use of methylprednisolone at 40 mg, use of methylprednisolone at 40 mg total dose, use of oral glucocorticoids, albumin level, and haemoglobin level) were screened using the LASSO algorithm and multivariate COX regression analysis. The PIP model built on these features performed reasonably well, with the developing C-index of 0.87 (sensitivity: 85.4%; specificity: 81.0%) and validation C-indices of 0.837, 0.829, 0.832 and 0.830 for predicting 90-, 180-, 270- and 360-day PI probability, respectively. The decision curve analysis (DCA) and calibration curves displayed excellent clinical utility and calibration performance of the nomogram. Conclusion: The PIP model presented herein could aid in the prediction of PI risk in individual patients who receive immunosuppressive treatment and help personalise clinical decision-making.
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Affiliation(s)
- Chuxuan Luo
- Department of Nephrology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou, Zhejiang, China
| | - Yue Zhang
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Jiajie Zhang
- Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Chen Jin
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Xiaolan Ye
- Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Yan Ren
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Huajuan Shen
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Maosheng Chen
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Yiwen Li
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Qiang He
- Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China
| | - Guangbiao Xu
- Department of Nephrology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou, Zhejiang, China
| | - Lina Shao
- Urology and Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
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10
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Jurgens SM, Prieto S, Hayes JP. Inflammatory biomarkers link perceived stress with metabolic dysregulation. Brain Behav Immun Health 2023; 34:100696. [PMID: 37928770 PMCID: PMC10623170 DOI: 10.1016/j.bbih.2023.100696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 10/13/2023] [Accepted: 10/16/2023] [Indexed: 11/07/2023] Open
Abstract
Objective Perceived stress has been identified as a risk factor for metabolic syndrome. However, the intermediate pathways underlying this relationship are not well understood. Inflammatory responses may be one process by which stress leads to metabolic dysregulation. Prior work has shown that chronic stress is associated with elevated systemic inflammation and that altered inflammatory activity contributes to the pathogenesis of metabolic syndrome. The current analyses tested this hypothesis by examining inflammation as a pathway by which perceived stress affects metabolic health. Methods Data from the Midlife in the United States Study (MIDUS) (N = 648; Mean age = 52.3) provided measures of perceived stress, inflammatory biomarkers [C-reactive protein (CRP), interleukin-6 (IL-6), E-selectin, fibrinogen, intracellular adhesion molecule-1 (ICAM-1)] and metabolic health markers. Confirmatory factor analysis (CFA) was used to confirm the fit of a hierarchical model of metabolic syndrome in our sample. Structural equation modeling (SEM) was used to test the assumption that inflammation mediates the association between perceived stress and the latent factor representing metabolic syndrome. Results The CFA of metabolic syndrome demonstrated excellent goodness of fit to our sample [CFI = 0.97, TLI = 0.95, RMSEA = 0.06, SMSR = 0.05]. Mediation analysis with SEM revealed that the indirect pathway linking stress to metabolic dysregulation through inflammation was significant [B = 0.08, SE = 0.01, z = 3.69, p < .001, 95% confidence interval CI (0.04, 0.13)]. Conclusions These results suggest that inflammatory biomarkers are a viable explanatory pathway for the relationship between perceived stress and metabolic health consequences. Interventions that target psychosocial stress may serve as cost-effective and accessible treatment options for mitigating inflammatory health risks.
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Affiliation(s)
- Savana M. Jurgens
- Department of Psychology, The Ohio State University, Columbus, OH, United States
| | - Sarah Prieto
- Department of Psychology, The Ohio State University, Columbus, OH, United States
| | - Jasmeet P. Hayes
- Department of Psychology, The Ohio State University, Columbus, OH, United States
- Chronic Brain Injury Initiative, The Ohio State University, Columbus, OH, United States
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11
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Poser M, Sing KEA, Ebert T, Ziebolz D, Schmalz G. The rosetta stone of successful ageing: does oral health have a role? Biogerontology 2023; 24:867-888. [PMID: 37421489 PMCID: PMC10615965 DOI: 10.1007/s10522-023-10047-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 06/19/2023] [Indexed: 07/10/2023]
Abstract
Ageing is an inevitable aspect of life and thus successful ageing is an important focus of recent scientific efforts. The biological process of ageing is mediated through the interaction of genes with environmental factors, increasing the body's susceptibility to insults. Elucidating this process will increase our ability to prevent and treat age-related disease and consequently extend life expectancy. Notably, centenarians offer a unique perspective on the phenomenon of ageing. Current research highlights several age-associated alterations on the genetic, epigenetic and proteomic level. Consequently, nutrient sensing and mitochondrial function are altered, resulting in inflammation and exhaustion of regenerative ability.Oral health, an important contributor to overall health, remains underexplored in the context of extreme longevity. Good masticatory function ensures sufficient nutrient uptake, reducing morbidity and mortality in old age. The relationship between periodontal disease and systemic inflammatory pathologies is well established. Diabetes, rheumatoid arthritis and cardiovascular disease are among the most significant disease burdens influenced by inflammatory oral health conditions. Evidence suggests that the interaction is bi-directional, impacting progression, severity and mortality. Current models of ageing and longevity neglect an important factor in overall health and well-being, a gap that this review intends to illustrate and inspire avenues for future research.
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Affiliation(s)
- Maximilian Poser
- Department of Cariology, Endodontology and Periodontology, University Leipzig, Liebigstr. 12, 04103, Leipzig, Germany.
| | - Katie E A Sing
- Department of Medicine, Royal Devon and Exeter Hospital, University of Exeter Medical School, Exeter, EX2 5DW, UK
| | - Thomas Ebert
- Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany
| | - Dirk Ziebolz
- Department of Cariology, Endodontology and Periodontology, University Leipzig, Liebigstr. 12, 04103, Leipzig, Germany
| | - Gerhard Schmalz
- Department of Cariology, Endodontology and Periodontology, University Leipzig, Liebigstr. 12, 04103, Leipzig, Germany
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12
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Bao H, Cao J, Chen M, Chen M, Chen W, Chen X, Chen Y, Chen Y, Chen Y, Chen Z, Chhetri JK, Ding Y, Feng J, Guo J, Guo M, He C, Jia Y, Jiang H, Jing Y, Li D, Li J, Li J, Liang Q, Liang R, Liu F, Liu X, Liu Z, Luo OJ, Lv J, Ma J, Mao K, Nie J, Qiao X, Sun X, Tang X, Wang J, Wang Q, Wang S, Wang X, Wang Y, Wang Y, Wu R, Xia K, Xiao FH, Xu L, Xu Y, Yan H, Yang L, Yang R, Yang Y, Ying Y, Zhang L, Zhang W, Zhang W, Zhang X, Zhang Z, Zhou M, Zhou R, Zhu Q, Zhu Z, Cao F, Cao Z, Chan P, Chen C, Chen G, Chen HZ, Chen J, Ci W, Ding BS, Ding Q, Gao F, Han JDJ, Huang K, Ju Z, Kong QP, Li J, Li J, Li X, Liu B, Liu F, Liu L, Liu Q, Liu Q, Liu X, Liu Y, Luo X, Ma S, Ma X, Mao Z, Nie J, Peng Y, Qu J, Ren J, Ren R, Song M, Songyang Z, Sun YE, Sun Y, Tian M, Wang S, et alBao H, Cao J, Chen M, Chen M, Chen W, Chen X, Chen Y, Chen Y, Chen Y, Chen Z, Chhetri JK, Ding Y, Feng J, Guo J, Guo M, He C, Jia Y, Jiang H, Jing Y, Li D, Li J, Li J, Liang Q, Liang R, Liu F, Liu X, Liu Z, Luo OJ, Lv J, Ma J, Mao K, Nie J, Qiao X, Sun X, Tang X, Wang J, Wang Q, Wang S, Wang X, Wang Y, Wang Y, Wu R, Xia K, Xiao FH, Xu L, Xu Y, Yan H, Yang L, Yang R, Yang Y, Ying Y, Zhang L, Zhang W, Zhang W, Zhang X, Zhang Z, Zhou M, Zhou R, Zhu Q, Zhu Z, Cao F, Cao Z, Chan P, Chen C, Chen G, Chen HZ, Chen J, Ci W, Ding BS, Ding Q, Gao F, Han JDJ, Huang K, Ju Z, Kong QP, Li J, Li J, Li X, Liu B, Liu F, Liu L, Liu Q, Liu Q, Liu X, Liu Y, Luo X, Ma S, Ma X, Mao Z, Nie J, Peng Y, Qu J, Ren J, Ren R, Song M, Songyang Z, Sun YE, Sun Y, Tian M, Wang S, Wang S, Wang X, Wang X, Wang YJ, Wang Y, Wong CCL, Xiang AP, Xiao Y, Xie Z, Xu D, Ye J, Yue R, Zhang C, Zhang H, Zhang L, Zhang W, Zhang Y, Zhang YW, Zhang Z, Zhao T, Zhao Y, Zhu D, Zou W, Pei G, Liu GH. Biomarkers of aging. SCIENCE CHINA. LIFE SCIENCES 2023; 66:893-1066. [PMID: 37076725 PMCID: PMC10115486 DOI: 10.1007/s11427-023-2305-0] [Show More Authors] [Citation(s) in RCA: 163] [Impact Index Per Article: 81.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 02/27/2023] [Indexed: 04/21/2023]
Abstract
Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant.
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Affiliation(s)
- Hainan Bao
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, China
| | - Jiani Cao
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Mengting Chen
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, China
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Min Chen
- Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Clinical Research Center of Metabolic and Cardiovascular Disease, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Wei Chen
- Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China
| | - Xiao Chen
- Department of Nuclear Medicine, Daping Hospital, Third Military Medical University, Chongqing, 400042, China
| | - Yanhao Chen
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Yu Chen
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Yutian Chen
- The Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
| | - Zhiyang Chen
- Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Ageing and Regenerative Medicine, Jinan University, Guangzhou, 510632, China
| | - Jagadish K Chhetri
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
| | - Yingjie Ding
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Junlin Feng
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Jun Guo
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, 100730, China
| | - Mengmeng Guo
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China
| | - Chuting He
- University of Chinese Academy of Sciences, Beijing, 100049, China
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China
| | - Yujuan Jia
- Department of Neurology, First Affiliated Hospital, Shanxi Medical University, Taiyuan, 030001, China
| | - Haiping Jiang
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China
| | - Ying Jing
- Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Advanced Innovation Center for Human Brain Protection, and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China
| | - Dingfeng Li
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230036, China
| | - Jiaming Li
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Jingyi Li
- University of Chinese Academy of Sciences, Beijing, 100049, China
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China
| | - Qinhao Liang
- College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430072, China
| | - Rui Liang
- Research Institute of Transplant Medicine, Organ Transplant Center, NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, 300384, China
| | - Feng Liu
- MOE Key Laboratory of Gene Function and Regulation, Guangzhou Key Laboratory of Healthy Aging Research, School of Life Sciences, Institute of Healthy Aging Research, Sun Yat-sen University, Guangzhou, 510275, China
| | - Xiaoqian Liu
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China
| | - Zuojun Liu
- School of Life Sciences, Hainan University, Haikou, 570228, China
| | - Oscar Junhong Luo
- Department of Systems Biomedical Sciences, School of Medicine, Jinan University, Guangzhou, 510632, China
| | - Jianwei Lv
- School of Life Sciences, Xiamen University, Xiamen, 361102, China
| | - Jingyi Ma
- The State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Kehang Mao
- Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, 100871, China
| | - Jiawei Nie
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine (Shanghai), International Center for Aging and Cancer, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Xinhua Qiao
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Xinpei Sun
- Peking University International Cancer Institute, Health Science Center, Peking University, Beijing, 100101, China
| | - Xiaoqiang Tang
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
| | - Jianfang Wang
- Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China
| | - Qiaoran Wang
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Siyuan Wang
- Clinical Research Institute, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China
| | - Xuan Wang
- Hepatobiliary and Pancreatic Center, Medical Research Center, Beijing Tsinghua Changgung Hospital, Beijing, 102218, China
| | - Yaning Wang
- Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China
- Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China
| | - Yuhan Wang
- University of Chinese Academy of Sciences, Beijing, 100049, China
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China
| | - Rimo Wu
- Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, China
| | - Kai Xia
- Center for Stem Cell Biologyand Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China
| | - Fu-Hui Xiao
- CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, 650223, China
- State Key Laboratory of Genetic Resources and Evolution, Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China
| | - Lingyan Xu
- Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China
| | - Yingying Xu
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, China
| | - Haoteng Yan
- Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
- Advanced Innovation Center for Human Brain Protection, and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China
| | - Liang Yang
- CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, 510530, China
| | - Ruici Yang
- State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China
| | - Yuanxin Yang
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 201210, China
| | - Yilin Ying
- Department of Geriatrics, Medical Center on Aging of Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- International Laboratory in Hematology and Cancer, Shanghai Jiao Tong University School of Medicine/Ruijin Hospital, Shanghai, 200025, China
| | - Le Zhang
- Gerontology Center of Hubei Province, Wuhan, 430000, China
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Weiwei Zhang
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China
| | - Wenwan Zhang
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Xing Zhang
- Key Laboratory of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, China
| | - Zhuo Zhang
- Optogenetics & Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China
- Research Unit of New Techniques for Live-cell Metabolic Imaging, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Min Zhou
- Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, China
| | - Rui Zhou
- Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Qingchen Zhu
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200031, China
| | - Zhengmao Zhu
- Department of Genetics and Cell Biology, College of Life Science, Nankai University, Tianjin, 300071, China
- Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China
| | - Feng Cao
- Department of Cardiology, The Second Medical Centre, Chinese PLA General Hospital, National Clinical Research Center for Geriatric Diseases, Beijing, 100853, China.
| | - Zhongwei Cao
- State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
| | - Piu Chan
- National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
| | - Chang Chen
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
| | - Guobing Chen
- Department of Microbiology and Immunology, School of Medicine, Jinan University, Guangzhou, 510632, China.
- Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, Guangzhou, 510000, China.
| | - Hou-Zao Chen
- Department of Biochemistryand Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
| | - Jun Chen
- Peking University Research Center on Aging, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, Department of Integration of Chinese and Western Medicine, School of Basic Medical Science, Peking University, Beijing, 100191, China.
| | - Weimin Ci
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, China.
| | - Bi-Sen Ding
- State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
| | - Qiurong Ding
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
| | - Feng Gao
- Key Laboratory of Ministry of Education, School of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, China.
| | - Jing-Dong J Han
- Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, 100871, China.
| | - Kai Huang
- Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Clinical Research Center of Metabolic and Cardiovascular Disease, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Zhenyu Ju
- Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Ageing and Regenerative Medicine, Jinan University, Guangzhou, 510632, China.
| | - Qing-Peng Kong
- CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, 650223, China.
- State Key Laboratory of Genetic Resources and Evolution, Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Key Laboratory of Healthy Aging Study, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
| | - Ji Li
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, China.
- Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, 410008, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.
| | - Jian Li
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, 100730, China.
| | - Xin Li
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
| | - Baohua Liu
- School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen, 518060, China.
| | - Feng Liu
- Metabolic Syndrome Research Center, The Second Xiangya Hospital, Central South Unversity, Changsha, 410011, China.
| | - Lin Liu
- Department of Genetics and Cell Biology, College of Life Science, Nankai University, Tianjin, 300071, China.
- Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
- Institute of Translational Medicine, Tianjin Union Medical Center, Nankai University, Tianjin, 300000, China.
- State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, China.
| | - Qiang Liu
- Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230036, China.
| | - Qiang Liu
- Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
- Tianjin Institute of Immunology, Tianjin Medical University, Tianjin, 300070, China.
| | - Xingguo Liu
- CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, 510530, China.
| | - Yong Liu
- College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430072, China.
| | - Xianghang Luo
- Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, China.
| | - Shuai Ma
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
| | - Xinran Ma
- Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
| | - Zhiyong Mao
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
| | - Jing Nie
- The State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
| | - Yaojin Peng
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
| | - Jing Qu
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
| | - Jie Ren
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
| | - Ruibao Ren
- Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine (Shanghai), International Center for Aging and Cancer, Collaborative Innovation Center of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
- International Center for Aging and Cancer, Hainan Medical University, Haikou, 571199, China.
| | - Moshi Song
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
| | - Zhou Songyang
- MOE Key Laboratory of Gene Function and Regulation, Guangzhou Key Laboratory of Healthy Aging Research, School of Life Sciences, Institute of Healthy Aging Research, Sun Yat-sen University, Guangzhou, 510275, China.
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
| | - Yi Eve Sun
- Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
| | - Yu Sun
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200031, China.
- Department of Medicine and VAPSHCS, University of Washington, Seattle, WA, 98195, USA.
| | - Mei Tian
- Human Phenome Institute, Fudan University, Shanghai, 201203, China.
| | - Shusen Wang
- Research Institute of Transplant Medicine, Organ Transplant Center, NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, 300384, China.
| | - Si Wang
- Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
- Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
- Advanced Innovation Center for Human Brain Protection, and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China.
| | - Xia Wang
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.
| | - Xiaoning Wang
- Institute of Geriatrics, The second Medical Center, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China.
| | - Yan-Jiang Wang
- Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
| | - Yunfang Wang
- Hepatobiliary and Pancreatic Center, Medical Research Center, Beijing Tsinghua Changgung Hospital, Beijing, 102218, China.
| | - Catherine C L Wong
- Clinical Research Institute, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China.
| | - Andy Peng Xiang
- Center for Stem Cell Biologyand Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080, China.
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
| | - Yichuan Xiao
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200031, China.
| | - Zhengwei Xie
- Peking University International Cancer Institute, Health Science Center, Peking University, Beijing, 100101, China.
- Beijing & Qingdao Langu Pharmaceutical R&D Platform, Beijing Gigaceuticals Tech. Co. Ltd., Beijing, 100101, China.
| | - Daichao Xu
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 201210, China.
| | - Jing Ye
- Department of Geriatrics, Medical Center on Aging of Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
- International Laboratory in Hematology and Cancer, Shanghai Jiao Tong University School of Medicine/Ruijin Hospital, Shanghai, 200025, China.
| | - Rui Yue
- Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
| | - Cuntai Zhang
- Gerontology Center of Hubei Province, Wuhan, 430000, China.
- Institute of Gerontology, Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Hongbo Zhang
- Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
- Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
| | - Liang Zhang
- CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, 200031, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
| | - Weiqi Zhang
- CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
| | - Yong Zhang
- Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, China.
- The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
| | - Yun-Wu Zhang
- Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, 361102, China.
| | - Zhuohua Zhang
- Key Laboratory of Molecular Precision Medicine of Hunan Province and Center for Medical Genetics, Institute of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, 410078, China.
- Department of Neurosciences, Hengyang Medical School, University of South China, Hengyang, 421001, China.
| | - Tongbiao Zhao
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
| | - Yuzheng Zhao
- Optogenetics & Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
- Research Unit of New Techniques for Live-cell Metabolic Imaging, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Dahai Zhu
- Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, China.
- The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
| | - Weiguo Zou
- State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
| | - Gang Pei
- Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Biomedicine, The Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai, 200070, China.
| | - Guang-Hui Liu
- University of Chinese Academy of Sciences, Beijing, 100049, China.
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
- Advanced Innovation Center for Human Brain Protection, and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China.
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13
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Zavatta A, Parisi F, Mandò C, Scaccabarozzi C, Savasi VM, Cetin I. Role of Inflammaging on the Reproductive Function and Pregnancy. Clin Rev Allergy Immunol 2023; 64:145-160. [PMID: 35031955 PMCID: PMC8760119 DOI: 10.1007/s12016-021-08907-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2021] [Indexed: 12/14/2022]
Abstract
During female lifetime and pregnancy, inflammation and cellular senescence are implicated in physiological processes, from ovulation and menstruation, to placental homeostasis and delivery. Several lifestyles, nutritional, and environmental insults, as well as long-lasting pregestational inflammatory diseases may lead to detrimental effects in promoting and sustaining a chronic excessive inflammatory response and inflammaging, which finally contribute to the decay of fertility and pregnancy outcome, with a negative effect on placental function, fetal development, and future health risk profile in the offspring. Maladaptation to pregnancy and obstetric disease may in turn increase maternal inflammaging in a feedback loop, speeding up aging processes and outbreak of chronic diseases. Maternal inflammaging may also impact, through transgenerational effects, on future adult health. Hence, efficacious interventions should be implemented by physicians and healthcare professionals involved in prevention activities to reduce the modifiable factors contributing to the inflammaging process in order to improve public health.
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Affiliation(s)
- Alice Zavatta
- Department of Woman Mother and Neonate 'V. Buzzi' Children Hospital, ASST Fatebenefratelli Sacco, 20154, Milan, Italy
- Department of Woman Mother and Neonate 'L. Sacco' Hospital, ASST Fatebenefratelli Sacco, 20157, Milan, Italy
| | - Francesca Parisi
- Department of Woman Mother and Neonate 'V. Buzzi' Children Hospital, ASST Fatebenefratelli Sacco, 20154, Milan, Italy
| | - Chiara Mandò
- Department of Biomedical and Clinical Sciences, "Luigi Sacco", University of Milan, 20157, Milan, Italy
| | - Chiara Scaccabarozzi
- Department of Woman Mother and Neonate 'L. Sacco' Hospital, ASST Fatebenefratelli Sacco, 20157, Milan, Italy
| | - Valeria M Savasi
- Department of Biomedical and Clinical Sciences, "Luigi Sacco", University of Milan, 20157, Milan, Italy
- Department of Woman Mother and Neonate 'L. Sacco' Hospital, ASST Fatebenefratelli Sacco, 20157, Milan, Italy
| | - Irene Cetin
- Department of Woman Mother and Neonate 'V. Buzzi' Children Hospital, ASST Fatebenefratelli Sacco, 20154, Milan, Italy.
- Department of Biomedical and Clinical Sciences, "Luigi Sacco", University of Milan, 20157, Milan, Italy.
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14
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Zöphel D, Kaschek L, Steiner R, Janku S, Chang HF, Lis A. Heterozygous OT-I mice reveal that antigen-specific CD8 + T cells shift from apoptotic to necrotic killers in the elderly. Aging Cell 2023:e13824. [PMID: 36947105 DOI: 10.1111/acel.13824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 02/24/2023] [Accepted: 02/24/2023] [Indexed: 03/23/2023] Open
Abstract
Numerous alterations in CD8+ T cells contribute to impaired immune responses in elderly individuals. However, the discrimination between cell-intrinsic dysfunctions and microenvironmental changes is challenging. TCR transgenic OT-I mice are utilized to investigate CD8+ T-cell immunity, but their immunodeficient phenotype hampers their use especially in aging. Here, we demonstrate that using a heterozygous OT-I model minimizes the current limitations and provides a valuable tool to assess antigen-specific T-cell responses even at old age. We analyzed phenotypic and functional characteristics of CD8+ T cells from OT-I+/+ and OT-I+/- mice to prove the applicability of the heterozygous system. Our data reveal that OVA-activated CD8+ T cells from adult OT-I+/- mice proliferate, differentiate, and exert cytolytic activity equally to their homozygous counterparts. Moreover, common age-related alterations in CD8+ T cells, including naive T-cell deterioration and decreased proliferative capacity, also occur in elderly OT-I+/- mice, indicating the wide range of applications for in vivo and in vitro aging studies. We used the OT-I+/- model to investigate cell-intrinsic alterations affecting the cytotoxic behavior of aged CD8+ T cells after antigen-specific in vitro activation. Time-resolved analysis of antigen-directed target cell lysis confirmed previous observations that the cytotoxic capacity of CD8+ T cells increases with age. Surprisingly, detailed single cell analysis revealed that transcriptional upregulation of perforin in aged CD8+ T cells shifts the mode of target cell death from granzyme-mediated apoptosis to rapid induction of necrosis. This unexpected capability might be beneficial or detrimental for the aging host and requires detailed evaluation.
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Affiliation(s)
- Dorina Zöphel
- Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421, Homburg, Germany
| | - Lea Kaschek
- Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421, Homburg, Germany
| | - Romy Steiner
- Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421, Homburg, Germany
| | - Sandra Janku
- Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421, Homburg, Germany
| | - Hsin-Fang Chang
- Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, Homburg, Germany
| | - Annette Lis
- Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Saarland University, 66421, Homburg, Germany
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15
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Kurai D, Song J, Huang YC, Jie Z, Atanasov P, Jiang X, Hernandez-Pastor L, Huang THW, Park S, Lim K, Richmond PC. Targeted Literature Review of the Burden of Respiratory Syncytial Infection among High-Risk and Elderly Patients in Asia Pacific Region. Infect Dis Ther 2023; 12:807-828. [PMID: 36869266 PMCID: PMC10017894 DOI: 10.1007/s40121-023-00777-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 02/09/2023] [Indexed: 03/05/2023] Open
Abstract
INTRODUCTION The burden of respiratory syncytial virus (RSV), which causes acute respiratory illness, is well recognized among the pediatric population but also imposes a significant risk to the elderly (age ≥ 60) and those with underlying comorbidities. The study aimed to review the most recent data on epidemiology and burden (clinical and economic) of RSV in the elderly/high-risk populations in China, Japan, South Korea, Taiwan, and Australia. METHODS A targeted review was conducted of English, Japanese, Korean, and Chinese language articles published from 1 January 2010 to 7 October 2020 relevant for the purpose. RESULTS A total of 881 studies were identified, and 41 were included. The median proportion of elderly patients with RSV in all adult patients with acute respiratory infection (ARI) or community acquired pneumonia was 79.78% (71.43-88.12%) in Japan, 48.00% (3.64-80.00%) in China, 41.67% (33.33-50.00%) in Taiwan, 38.61% in Australia, and 28.57% (22.76-33.33%) in South Korea. RSV was associated with a high clinical burden on those patients with comorbidities such as asthma and chronic obstructive pulmonary disease. In China, inpatients with ARI showed a significantly higher rate of RSV-related hospitalization than outpatients (13.22% versus 4.08%, p < 0.01). The median length of hospital stay among elderly patients with RSV was longest in Japan (30 days) and shortest in China (7 days). Mortality data varied by region with some studies reporting rates as high as 12.00% (9/75) in hospitalized elderly patients. Finally, data on the economic burden was only available for South Korea, with the median cost of a medical admission for an elderly patient with RSV being US dollar (USD) 2933. CONCLUSION RSV infection is a major source of disease burden among elderly patients, especially in regions with aging populations. It also complicates the management of those with underlying diseases. Appropriate prevention strategies are required to reduce the burden among the adult, especially the elderly, population. Data gaps regarding economic burden of RSV infection in the Asia Pacific region indicates the need for further research to increase our understanding on the burden of this disease in this region.
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Affiliation(s)
| | - JoonYoung Song
- Korea University College of Medicine, Seoul, South Korea
| | | | - Zhijun Jie
- Department of Pulmonary and Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
| | - Petar Atanasov
- Health Economics and Market Access, Amaris Consulting, Barcelona, Spain
| | - Xiaobin Jiang
- Health Economics and Market Access, Amaris Consulting, Shanghai, China
| | | | | | | | - KyungHwa Lim
- Asia Pacific Market Access, Janssen Pharmaceuticals, Seoul, South Korea
| | - Peter C Richmond
- University of Western Australia Medical School, 35 Stirling Highway, Perth, WA, 6009, Australia.
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16
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Lorefice L, D’Alterio MN, Firinu D, Fenu G, Cocco E. Impact of Menopause in Patients with Multiple Sclerosis: Current Perspectives. Int J Womens Health 2023; 15:103-109. [PMID: 36721498 PMCID: PMC9884461 DOI: 10.2147/ijwh.s334719] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 01/18/2023] [Indexed: 01/26/2023] Open
Abstract
Given the aging population, with a peak age-specific prevalence that is shifting beyond the age of 50, several women currently living with MS are very close to menopause. Menopause is usually characterized by several specific symptoms with adverse impacts on different aspects of a woman's quality of life, such as fatigue, and cognitive, mood and bladder disorders, which overlap with symptoms of MS. Generally, after this biological transition, women with MS appear to be subject to less inflammatory activity. However, several studies have reported an increase of disability accumulation after menopause, suggesting that it is a turning point to a more progressive phase of the disease. This may be attributable to the hormonal and immunological changes associated with menopause, with several effects on neuroinflammation and neurodegeneration increasing due to the immunosenescence of aging. This review summarizes the hormonal and immunological changes associated with menopause, detailing the effects on MS symptoms, outcomes, and the aging process. Furthermore, possible interventions to improve patients' quality of life are evaluated. In fact, it is increasingly necessary to improve the global management of MS women, as well as their lives, at this multifaceted turning point.
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Affiliation(s)
- Lorena Lorefice
- Multiple Sclerosis Center, Binaghi Hospital, ASL Cagliari, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Maurizio Nicola D’Alterio
- Division of Gynecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | - Davide Firinu
- Clinical Immunology, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Giuseppe Fenu
- Department of Neurosciences, ARNAS Brotzu, Cagliari, Italy
| | - Eleonora Cocco
- Multiple Sclerosis Center, Binaghi Hospital, ASL Cagliari, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
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17
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Kunz AL, Schönstein A, Bahrmann P, Giannitsis E, Wahl HW, Katus HA, Frey N, Bahrmann A. Exploring biomarkers in routine diagnostics for the risk stratification of older patients in the Chest Pain Unit: a prospective cohort study. BMJ Open 2022; 12:e056674. [PMID: 36572487 PMCID: PMC9806057 DOI: 10.1136/bmjopen-2021-056674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES This study aims to estimate the association of the often, in daily clinical practice, used biological age-related biomarkers high-sensitivity troponin-T (hs-TnT), C reactive protein (CRP) and haemoglobin (Hb) with all-cause mortality for the purpose of older patient's risk stratification in the emergency department (ED). DESIGN Exploratory, prospective cohort study with a follow-up at 2.5 years after recruitment started. For the predictors, data from the hospital files including the routinely applied biological age-related biomarkers hs-TnT, CRP and Hb were supplemented by a questionnaire. SETTING A cardiological ED, Chest Pain Unit, University Hospital Heidelberg, Germany. PARTICIPANTS N=256 cardiological ED patients with a minimum age of 70 years and the capability to informed consent. PRIMARY OUTCOME MEASURES The primary outcome of this study was all-cause mortality which was assessed by requesting registry office information. RESULTS Among N=256 patients 63 died over the follow-up period. Positive results in each of the three biomarkers alone as well as the combination were associated with increased all-cause mortality at follow-up. The number of positive age-related biomarkers appeared to be strongly indicative of the risk of mortality, even when controlled for major confounders (age, sex, body mass index, creatinine clearance and comorbidity). CONCLUSIONS In older ED patients, biomarkers explicitly related to biological ageing processes such as hs-TnT, CRP and Hb were to a certain degree independently of each other as well as combined associated with an increased risk of all-cause mortality. Thus, they may have the potential to be used to supplement the general risk stratification of older patients in the ED. Validation of the results in a large dataset is needed.
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Affiliation(s)
- Anna Lisa Kunz
- Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany
| | - Anton Schönstein
- Network Aging Research, Heidelberg University, Heidelberg, Germany
| | - Philipp Bahrmann
- Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany
| | - Evangelos Giannitsis
- Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany
| | - Hans-Werner Wahl
- Network Aging Research and Institute of Psychology, Heidelberg University, Heidelberg, Germany
| | - Hugo A Katus
- Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany
| | - Norbert Frey
- Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany
| | - Anke Bahrmann
- Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany
- Network Aging Research, Heidelberg University, Heidelberg, Germany
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18
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Immunosenescence and Aging: Neuroinflammation Is a Prominent Feature of Alzheimer's Disease and Is a Likely Contributor to Neurodegenerative Disease Pathogenesis. J Pers Med 2022; 12:jpm12111817. [PMID: 36579548 PMCID: PMC9698256 DOI: 10.3390/jpm12111817] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 10/25/2022] [Accepted: 10/29/2022] [Indexed: 11/06/2022] Open
Abstract
Alzheimer's disease (AD) is a chronic multifactorial and complex neuro-degenerative disorder characterized by memory impairment and the loss of cognitive ability, which is a problem affecting the elderly. The pathological intracellular accumulation of abnormally phosphorylated Tau proteins, forming neurofibrillary tangles, and extracellular amyloid-beta (Aβ) deposition, forming senile plaques, as well as neural disconnection, neural death and synaptic dysfunction in the brain, are hallmark pathologies that characterize AD. The prevalence of the disease continues to increase globally due to the increase in longevity, quality of life, and medical treatment for chronic diseases that decreases the mortality and enhance the survival of elderly. Medical awareness and the accurate diagnosis of the disease also contribute to the high prevalence observed globally. Unfortunately, no definitive treatment exists that can be used to modify the course of AD, and no available treatment is capable of mitigating the cognitive decline or reversing the pathology of the disease as of yet. A plethora of hypotheses, ranging from the cholinergic theory and dominant Aβ cascade hypothesis to the abnormally excessive phosphorylated Tau protein hypothesis, have been reported. Various explanations for the pathogenesis of AD, such as the abnormal excitation of the glutamate system and mitochondrial dysfunction, have also been suggested. Despite the continuous efforts to deliver significant benefits and an effective treatment for this distressing, globally attested aging illness, multipronged approaches and strategies for ameliorating the disease course based on knowledge of the underpinnings of the pathogenesis of AD are urgently needed. Immunosenescence is an immune deficit process that appears with age (inflammaging process) and encompasses the remodeling of the lymphoid organs, leading to alterations in the immune function and neuroinflammation during advanced aging, which is closely linked to the outgrowth of infections, autoimmune diseases, and malignant cancers. It is well known that long-standing inflammation negatively influences the brain over the course of a lifetime due to the senescence of the immune system. Herein, we aim to trace the role of the immune system in the pathogenesis of AD. Thus, we explore alternative avenues, such as neuroimmune involvement in the pathogenesis of AD. We determine the initial triggers of neuroinflammation, which is an early episode in the pre-symptomatic stages of AD and contributes to the advancement of the disease, and the underlying key mechanisms of brain damage that might aid in the development of therapeutic strategies that can be used to combat this devastating disease. In addition, we aim to outline the ways in which different aspects of the immune system, both in the brain and peripherally, behave and thus to contribute to AD.
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19
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Naranjo-Galvis CA, Cardona-Londoño KY, Orrego-Cardozo M, Elcoroaristizabal-Martín X. Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets. Heliyon 2022; 8:e10576. [PMID: 36119857 PMCID: PMC9478394 DOI: 10.1016/j.heliyon.2022.e10576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 11/12/2021] [Accepted: 09/02/2022] [Indexed: 11/21/2022] Open
Abstract
Infections of humans with the protozoan parasite Toxoplasma gondii (T. gondii) can lead to the disease's development, even in an asymptomatic status. However, the mechanisms that result in these clinical outcomes after infection are poorly understood. This study aimed to explore the molecular pathogenesis of toxoplasmosis-related inflammation through next-generation sequencing, to assess RNA expression profiles in peripheral blood from 5 female patients with chronic toxoplasmosis and 5 healthy female controls. All plasma samples were analyzed for anti-Toxoplasma IgG and IgM antibody titers by using electrochemiluminescence. Detection of acute and chronic toxoplasmosis was carried out using the ELISA IgG avidity. We evaluated the levels of INF-γ, IL-2, IL-12, TNF-α, IL-10, and IL-1β in culture supernatants of Peripheral Blood Mononuclear Cells infected with Toxoplasma lysate antigen (TLA) prepared with tachyzoites of strain T. gondii RH. Differential expression analysis was performed using DESeq2, pathway and enrichment analysis of DEGs was done on WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and Protein-protein interaction was carried out using NetworkAnalyst with STRING. In older people with chronic asymptomatic infection, a significant difference in the levels of inflammatory cytokines INF-γ and IL-2 was observed compared to seronegative individuals. Our results revealed differences in the regulation of critical biological processes involved in host responses to chronic T. gondii infection. Gene ontology analysis revealed several biologically relevant inflammatory and immune-related pathways.
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Affiliation(s)
- Carlos A Naranjo-Galvis
- Facultad de Salud, Universidad Autónoma de Manizales, Antigua Estación Del Ferrocarril, Manizales, Caldas, Colombia
| | - Kelly Y Cardona-Londoño
- Facultad de Salud, Universidad Autónoma de Manizales, Antigua Estación Del Ferrocarril, Manizales, Caldas, Colombia
| | - Mary Orrego-Cardozo
- Facultad de Salud, Universidad Autónoma de Manizales, Antigua Estación Del Ferrocarril, Manizales, Caldas, Colombia
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20
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Zheng HY, Wang XH, He XY, Chen M, Zhang MX, Lian XD, Song JH, Hu Y, Pang W, Wang Y, Hu ZF, Lv LB, Zheng YT. Aging induces severe SIV infection accompanied by an increase in follicular CD8+ T cells with overactive STAT3 signaling. Cell Mol Immunol 2022; 19:1042-1053. [PMID: 35851876 PMCID: PMC9424273 DOI: 10.1038/s41423-022-00899-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 06/23/2022] [Indexed: 11/09/2022] Open
Abstract
The number of elderly people living with HIV is increasing globally, and the condition of this population is relatively complicated due to the dual effects of aging and HIV infection. However, the impact of HIV infection combined with aging on the immune homeostasis of secondary lymphoid organs remains unclear. Here, we used the simian immunodeficiency virus mac239 (SIVmac239) strain to infect six young and six old Chinese rhesus macaques (ChRMs) and compared the infection characteristics of the two groups in the chronic stage through multiplex immunofluorescence staining of lymph nodes. The results showed that the SIV production and CD4/CD8 ratio inversion in old ChRMs were more severe than those in young ChRMs in both the peripheral blood and the lymph nodes, especially when a large number of CD8+ T cells infiltrated the follicles and germinal centers. STAT3 in these follicular CXCR5+CD8+ T cells was highly activated, with high expression of granzyme B, which might be caused by the severe inflammatory milieu in the follicles of old ChRMs. This study indicates that aging may be a cofactor involved in SIV-induced immune disorders in secondary lymphoid tissues, affecting the effective antiviral activity of highly enriched follicular CXCR5+CD8+ cells.
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Affiliation(s)
- Hong-Yi Zheng
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China
| | - Xue-Hui Wang
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China
- School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Xiao-Yan He
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China
- Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China
| | - Min Chen
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China
- Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China
| | - Ming-Xu Zhang
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China
- Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China
| | - Xiao-Dong Lian
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China
- Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China
| | - Jia-Hao Song
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China
- Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China
| | - Yan Hu
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China
- Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China
| | - Wei Pang
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China
| | - Yun Wang
- National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650107, China
| | - Zheng-Fei Hu
- National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650107, China
| | - Long-Bao Lv
- National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650107, China
| | - Yong-Tang Zheng
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China.
- School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, China.
- Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China.
- National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650107, China.
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Bichet C, Régis C, Gilot‐Fromont E, Cohas A. Variations in immune parameters with age in a wild rodent population and links with survival. Ecol Evol 2022; 12:e9094. [PMID: 35845372 PMCID: PMC9273568 DOI: 10.1002/ece3.9094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 06/14/2022] [Accepted: 06/20/2022] [Indexed: 12/02/2022] Open
Abstract
Recent findings suggest that immune functions do not unidirectionally deteriorate with age but that a potentially adaptive remodeling, where functions of the immune system get downregulated while others get upregulated with age could also occur. Scarce in wild populations, longitudinal studies are yet necessary to properly understand the patterns and consequences of age variations of the immune system in the wild. Meanwhile, it is challenging to understand if the observed variations in immune parameters with age are due to changes at the within-individual level or to selective (dis)appearance of individuals with peculiar immune phenotypes. Thanks to a long-term and longitudinal monitoring of a wild Alpine marmot population, we aimed to understand within- and between-individual variation in the immune phenotype with age, in order to improve our knowledge about the occurrence and the evolutionary consequences of such age variations in the wild. To do so, we recorded the age-specific leukocyte concentration and leukocyte profile in repeatedly sampled dominant individuals. We then tested whether the potential changes with age were attributable to within-individual variations and/or selective (dis)appearance. Finally, we investigated if the leukocyte concentration and profiles were correlated to the probability of death at a given age. The leukocyte concentration was stable with age, but the relative number of lymphocytes decreased, while the relative number of neutrophils increased, over the course of an individual's life. Moreover, between individuals of the same age, individuals with fewer lymphocytes but more neutrophils were more likely to die. Therefore, selective disappearance seems to play a role in the age variations of the immune parameters in this population. Further investigations linking age variations in immune phenotype to individual fitness are needed to understand whether remodeling of the immune system with age could or could not be adaptive.
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Affiliation(s)
- Coraline Bichet
- Centre d'Etudes Biologiques de ChizéCNRS‐La Rochelle UniversitéVilliers‐en‐BoisFrance
- Institut für Vogelforschung "Vogelwarte Helgoland" (Institute of Avian Research)WilhelmshavenGermany
- UMR‐CNRS 5558, Laboratoire Biométrie et Biologie ÉvolutiveUniversité Claude Bernard Lyon 1VilleurbanneFrance
| | - Corinne Régis
- UMR‐CNRS 5558, Laboratoire Biométrie et Biologie ÉvolutiveUniversité Claude Bernard Lyon 1VilleurbanneFrance
| | - Emmanuelle Gilot‐Fromont
- UMR‐CNRS 5558, Laboratoire Biométrie et Biologie ÉvolutiveUniversité Claude Bernard Lyon 1VilleurbanneFrance
- Université de Lyon, VetAgro SupMarcy‐l'EtoileFrance
| | - Aurélie Cohas
- UMR‐CNRS 5558, Laboratoire Biométrie et Biologie ÉvolutiveUniversité Claude Bernard Lyon 1VilleurbanneFrance
- Institut Universitaire de France (IUF)ParisFrance
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22
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Jeong J, Han JH, Choi HS, Moon IS. Immunoinflammatory and vascular inflammatory factors can be potential disease biomarkers of age-related hearing loss. EUR J INFLAMM 2022. [DOI: 10.1177/1721727x221110078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objectives: The relationship between age-related diseases and chronic inflammation associated with aging has recently been investigated. This study aimed to investigate how chronic inflammation is associated with age-related hearing loss (ARHL). Methods: Twenty ARHL patients aged ≥65 years were prospectively enrolled from July 1 to 31 December 2015. Audiological tests and serological tests, such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), immunoglobulin G (IgG), interleukin 6 (IL-6), white blood cell (WBC) counts, neutrophil counts, lymphocyte counts, and platelet counts, were performed. The patients were divided into two groups: mild hearing loss group (n = 7) and moderate to profound hearing loss group (n = 13). Results: Immunoinflammatory biomarkers, such as CRP, ESR, and IL-6, and vascular inflammatory biomarkers, such as neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, were higher in the moderate to profound hearing loss group. IgG, WBC counts, and neutrophil counts were similar in both groups. Conclusion: The present preliminary pilot study demonstrated that high levels of inflammatory biomarkers may be associated with ARHL. The results suggest a possible association between chronic inflammation and ARHL. Further well-designed studies of ARHL, based on a new perspective of chronic inflammation, should be performed.
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Affiliation(s)
- Junhui Jeong
- Department of Otorhinolaryngology, National Health Insurance Service Ilsan Hospital, Goyang, Korea
- Research Institute, Seoul Medical Center, Seoul, Korea
| | - Ji Hyuk Han
- Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Seung Choi
- Department of Otorhinolaryngology, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - In Seok Moon
- Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea
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Leposavić G, Stojić-Vukanić Z. Biomarkers of aging-associated chronic inflammation as a prognostic factor for human longevity. ARHIV ZA FARMACIJU 2022. [DOI: 10.5937/arhfarm72-36135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
It has been well-established that age-associated low-grade chronic inflammation contributes to the development of a spectrum of chronic diseases, including diabetes mellitus, ischemic heart disease, stroke, cancer, chronic kidney disease, non-alcoholic fatty liver disease and neurodegenerative diseases, which affect the quality of life of the elderly and influence their life span. This phenomenon is suggested to arise due to the weakening of the regulatory mechanisms of the immune response, and the persistence of exogenous and endogenous (reflecting oxidative cell injury) antigenic challenges, so it is referred to as oxi-inflamm-aging. Considering that the development of age-associated chronic inflammation is "silent", i.e., without clinical signs until the aforementioned complications become apparent, it is important to identify the biomarker(s) or pattern/cluster of biomarkers for this inflammation. It is also important to define new strategies to combat the "silent" damage induced by chronic inflammation. Given that at present there are no reliable biomarkers for chronic inflammation, this review points out the problems in defining biomarker(s) or patterns/clusters of biomarkers for chronic inflammation in order to stimulate further research and points to some possible routes of investigation.
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24
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Shen CY, Lu CH, Wu CH, Li KJ, Kuo YM, Hsieh SC, Yu CL. Molecular Basis of Accelerated Aging with Immune Dysfunction-Mediated Inflammation (Inflamm-Aging) in Patients with Systemic Sclerosis. Cells 2021; 10:cells10123402. [PMID: 34943909 PMCID: PMC8699891 DOI: 10.3390/cells10123402] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/17/2021] [Accepted: 11/30/2021] [Indexed: 12/17/2022] Open
Abstract
Systemic sclerosis (SSc) is a chronic connective tissue disorder characterized by immune dysregulation, chronic inflammation, vascular endothelial cell dysfunction, and progressive tissue fibrosis of the skin and internal organs. Moreover, increased cancer incidence and accelerated aging are also found. The increased cancer incidence is believed to be a result of chromosome instability. Accelerated cellular senescence has been confirmed by the shortening of telomere length due to increased DNA breakage, abnormal DNA repair response, and telomerase deficiency mediated by enhanced oxidative/nitrative stresses. The immune dysfunctions of SSc patients are manifested by excessive production of proinflammatory cytokines IL-1, IL-6, IL-17, IFN-α, and TNF-α, which can elicit potent tissue inflammation followed by tissue fibrosis. Furthermore, a number of autoantibodies including anti-topoisomerase 1 (anti-TOPO-1), anti-centromere (ACA or anti-CENP-B), anti-RNA polymerase enzyme (anti-RNAP III), anti-ribonuclear proteins (anti-U1, U2, and U11/U12 RNP), anti-nucleolar antigens (anti-Th/T0, anti-NOR90, anti-Ku, anti-RuvBL1/2, and anti-PM/Scl), and anti-telomere-associated proteins were also found. Based on these data, inflamm-aging caused by immune dysfunction-mediated inflammation exists in patients with SSc. Hence, increased cellular senescence is elicited by the interactions among excessive oxidative stress, pro-inflammatory cytokines, and autoantibodies. In the present review, we will discuss in detail the molecular basis of chromosome instability, increased oxidative stress, and functional adaptation by deranged immunome, which are related to inflamm-aging in patients with SSc.
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Affiliation(s)
- Chieh-Yu Shen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-H.W.); (K.-J.L.); (Y.-M.K.)
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan
| | - Cheng-Hsun Lu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-H.W.); (K.-J.L.); (Y.-M.K.)
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan
| | - Cheng-Han Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-H.W.); (K.-J.L.); (Y.-M.K.)
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan
| | - Ko-Jen Li
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-H.W.); (K.-J.L.); (Y.-M.K.)
| | - Yu-Min Kuo
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-H.W.); (K.-J.L.); (Y.-M.K.)
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan
| | - Song-Chou Hsieh
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-H.W.); (K.-J.L.); (Y.-M.K.)
- Correspondence: (S.-C.H.); (C.-L.Y.); Tel.: +886-2-23123456 (S.-C.H. & C.-L.Y.)
| | - Chia-Li Yu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-H.W.); (K.-J.L.); (Y.-M.K.)
- Correspondence: (S.-C.H.); (C.-L.Y.); Tel.: +886-2-23123456 (S.-C.H. & C.-L.Y.)
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25
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Kramp LJ, Mathiak M, Behrens HM, Schäfer FW, van Mackelenbergh M, Röcken C. The age-specific differences in histopathological tumor characteristics and TNM classification of breast carcinomas in Quality assured mamma diagnostic (QuaMaDi) program in the state of Schleswig-Holstein in Germany. J Cancer Res Clin Oncol 2021; 148:387-400. [PMID: 34705105 PMCID: PMC8800883 DOI: 10.1007/s00432-021-03841-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 10/18/2021] [Indexed: 11/28/2022]
Abstract
Background We explored the hypothesis that high-quality standards in diagnostic mammography can lead to an early diagnosis of breast cancers and identifies at risk populations outside screening programs. The histopathological features and distribution of the TNM classification were examined in relation to patient age in a large group of women with breast cancers participating in the Quality Assured Mamma Diagnostic (QuaMaDi) program of the state of Schleswig–Holstein. Patients and methods Surgical pathological reports were studied for clinicopathological characteristics, receptor status, molecular subtype and tumor stage. The analysis was conducted by dividing the study population into three age groups: women under 50 years (pre-screening), 50–69 years (peri-screening) and over 70 years (post-screening). Results 7.111 biopsies and 2.887 resection specimens were included. Breast cancer was diagnosed in 4.241 (59.7%) cases, one fourth of them in women < 50 years. Elderly women (> 70 years) had more well-differentiated, estrogen receptor (ER)-positive and HER2-negative carcinomas, whereas younger women (< 50 years) tended to have more poorly differentiated, ER negative, and HER2-positive carcinomas. 47% of breast carcinoma were luminal B tumors and were most common regardless of age. 70.4% of resected specimen had pT1 stage. Nodal negative were 71.2%. Conclusion In QuaMaDi breast cancer was diagnosed at an early and potentially curable stage of the disease due to high-quality standards in diagnostic mammography. In addition, regardless of age, an increased number of prognostically unfavorable molecular subtypes were detected. Thus, QuaMaDi helps to identify at risk populations. QuaMaDi significantly improves diagnostic mammography and complements mammography screening programs. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-021-03841-x.
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Affiliation(s)
- L-J Kramp
- Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus U33, 24105, Kiel, Germany
| | - M Mathiak
- Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus U33, 24105, Kiel, Germany
| | - H-M Behrens
- Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus U33, 24105, Kiel, Germany
| | - F W Schäfer
- Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - M van Mackelenbergh
- Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Christoph Röcken
- Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus U33, 24105, Kiel, Germany.
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26
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Alqahtani SA, Schattenberg JM. NAFLD in the Elderly. Clin Interv Aging 2021; 16:1633-1649. [PMID: 34548787 PMCID: PMC8448161 DOI: 10.2147/cia.s295524] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 08/12/2021] [Indexed: 12/25/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent disease globally. Current estimates are that 24% of the adult population, thus, one billion individuals worldwide, are affected. Interestingly, the prevalence of fatty liver seems to peak between 40─50 years of age in males and 60─69 years in females, often slightly decreasing in older (>70 years) cohorts. Furthermore, several risk factors for NAFLD development, such as hypertension, diabetes, hyperlipidemia, and obesity are higher in older adults. The diagnosis and management strategies in older adults are sometimes challenging, and certain age-specific factors have to be taken into account by healthcare professionals. In this review, we provide an overview of considerations relevant to the management and diagnosis of NAFLD in older adults (age >65 years) and discuss the types of pharmacological interventions available for the management of non-alcoholic steatohepatitis (NASH) in the aging population.
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Affiliation(s)
- Saleh A Alqahtani
- Liver Transplantation Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.,Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Jörn M Schattenberg
- Metabolic Liver Research Program, I. Department of Medicine, University Medical Center, Mainz, Germany
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27
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Landay A, Bartley JM, Banerjee D, Hargis G, Haynes L, Keshavarzian A, Kuo CL, Kwon OS, Li S, Li S, Oh J, Ozbolat IT, Ucar D, Xu M, Yao X, Unutmaz D, Kuchel GA. Network Topology of Biological Aging and Geroscience-Guided Approaches to COVID-19. FRONTIERS IN AGING 2021; 2:695218. [PMID: 35128530 PMCID: PMC8813169 DOI: 10.3389/fragi.2021.695218] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 06/22/2021] [Indexed: 01/08/2023]
Abstract
Aging has emerged as the greatest and most prevalent risk factor for the development of severe COVID-19 infection and death following exposure to the SARS-CoV-2 virus. The presence of multiple co-existing chronic diseases and conditions of aging further enhances this risk. Biological aging not only enhances the risk of chronic diseases, but the presence of such conditions further accelerates varied biological processes or "hallmarks" implicated in aging. Given growing evidence that it is possible to slow the rate of many biological aging processes using pharmacological compounds has led to the proposal that such geroscience-guided interventions may help enhance immune resilience and improve outcomes in the face of SARS-CoV-2 infection. Our review of the literature indicates that most, if not all, hallmarks of aging may contribute to the enhanced COVID-19 vulnerability seen in frail older adults. Moreover, varied biological mechanisms implicated in aging do not function in isolation from each other, and exhibit intricate effects on each other. With all of these considerations in mind, we highlight limitations of current strategies mostly focused on individual single mechanisms, and we propose an approach which is far more multidisciplinary and systems-based emphasizing network topology of biological aging and geroscience-guided approaches to COVID-19.
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Affiliation(s)
- Alan Landay
- Department of Medicine, Rush School of Medicine, Chicago, IL, United States
| | - Jenna M. Bartley
- UConn Center on Aging, University of Connecticut School of Medicine, Farmington, CT, United States
- Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, United States
| | - Dishary Banerjee
- Engineering Science and Mechanics Department, The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, United States
| | - Geneva Hargis
- UConn Center on Aging, University of Connecticut School of Medicine, Farmington, CT, United States
| | - Laura Haynes
- UConn Center on Aging, University of Connecticut School of Medicine, Farmington, CT, United States
- Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, United States
| | - Ali Keshavarzian
- Division of Digestive Diseases, Departments of Medicine, Pharmacology, Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL, United States
| | - Chia-Ling Kuo
- UConn Center on Aging, University of Connecticut School of Medicine, Farmington, CT, United States
- Connecticut Convergence Institute for Translation in Regenerative Engineering, Storrs, CT, United States
| | - Oh Sung Kwon
- UConn Center on Aging, University of Connecticut School of Medicine, Farmington, CT, United States
- Department of Kinesiology, University of Connecticut, Storrs, CT, United States
| | - Sheng Li
- Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
- Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT, United States
| | - Shuzhao Li
- Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, United States
- Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
| | - Julia Oh
- Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
- Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT, United States
| | - Ibrahim Tarik Ozbolat
- Engineering Science and Mechanics Department, The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, United States
- Biomedical Engineering Department, Neurosurgery Department, Materials Research Institute, Penn State University, University Park, PA, United States
| | - Duygu Ucar
- Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
- Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT, United States
| | - Ming Xu
- UConn Center on Aging, University of Connecticut School of Medicine, Farmington, CT, United States
- Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT, United States
| | - Xudong Yao
- Department of Chemistry, University of Connecticut, Storrs, CT, United States
| | - Derya Unutmaz
- Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, United States
- Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
| | - George A. Kuchel
- UConn Center on Aging, University of Connecticut School of Medicine, Farmington, CT, United States
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Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination. Proc Natl Acad Sci U S A 2021; 118:2022928118. [PMID: 33811141 PMCID: PMC8040665 DOI: 10.1073/pnas.2022928118] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Chronic inflammation is thought to be a major cause of morbidity and mortality in aging, but whether similar mechanisms underlie dysfunction in infection-associated chronic inflammation is unclear. Here, we profiled the immune proteome, and cellular composition and signaling states in a cohort of aging individuals versus a set of HIV patients on long-term antiretroviral therapy therapy or hepatitis C virus (HCV) patients before and after sofosbuvir treatment. We found shared alterations in aging-associated and infection-associated chronic inflammation including T cell memory inflation, up-regulation of intracellular signaling pathways of inflammation, and diminished sensitivity to cytokines in lymphocytes and myeloid cells. In the HIV cohort, these dysregulations were evident despite viral suppression for over 10 y. Viral clearance in the HCV cohort partially restored cellular sensitivity to interferon-α, but many immune system alterations persisted for at least 1 y posttreatment. Our findings indicate that in the HIV and HCV cohorts, a broad remodeling and degradation of the immune system can persist for a year or more, even after the removal or drastic reduction of the pathogen load and that this shares some features of chronic inflammation in aging.
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29
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Berben L, Floris G, Wildiers H, Hatse S. Cancer and Aging: Two Tightly Interconnected Biological Processes. Cancers (Basel) 2021; 13:1400. [PMID: 33808654 PMCID: PMC8003441 DOI: 10.3390/cancers13061400] [Citation(s) in RCA: 124] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/15/2021] [Accepted: 03/17/2021] [Indexed: 02/07/2023] Open
Abstract
Age is one of the main risk factors of cancer; several biological changes linked with the aging process can explain this. As our population is progressively aging, the proportion of older patients with cancer is increasing significantly. Due to the heterogeneity of general health and functional status amongst older persons, treatment of cancer is a major challenge in this vulnerable population. Older patients often experience more side effects of anticancer treatments. Over-treatment should be avoided to ensure an optimal quality of life. On the other hand, under-treatment due to fear of toxicity is a frequent problem and can lead to an increased risk of relapse and worse survival. There is a delicate balance between benefits of therapy and risk of toxicity. Robust biomarkers that reflect the body's biological age may aid in outlining optimal individual treatment regimens for older patients with cancer. In particular, the impact of age on systemic immunity and the tumor immune infiltrate should be considered, given the expanding role of immunotherapy in cancer treatment. In this review, we summarize current knowledge concerning the mechanistic connections between aging and cancer, as well as aging biomarkers that could be helpful in the field of geriatric oncology.
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Affiliation(s)
- Lieze Berben
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium;
| | - Giuseppe Floris
- Department of Pathology, University Hospitals Leuven, 3000 Leuven, Belgium;
- Laboratory of Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium
| | - Hans Wildiers
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium;
- Department of General Medical Oncology, University Hospitals Leuven, 3000 Leuven, Belgium
| | - Sigrid Hatse
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium;
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Hallmarks of aging and immunosenescence: Connecting the dots. Cytokine Growth Factor Rev 2021; 59:9-21. [PMID: 33551332 DOI: 10.1016/j.cytogfr.2021.01.006] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 01/24/2021] [Indexed: 12/11/2022]
Abstract
Aging is a natural physiological process that features various and variable challenges, associated with loss of homeostasis within the organism, often leading to negative consequences for health. Cellular senescence occurs when cells exhaust the capacity to renew themselves and their tissue environment as the cell cycle comes to a halt. This process is influenced by genetics, metabolism and extrinsic factors. Immunosenescence, the aging of the immune system, is a result of the aging process, but can also in turn act as a secondary inducer of senescence within other tissues. This review aims to summarize the current state of knowledge regarding hallmarks of aging in relation to immunosenescence, with a focus on aging-related imbalances in the medullary environment, as well as the components of the innate and adaptive immune responses. Aging within the immune system alters its functionality, and has consequences for the person's ability to fight infections, as well as for susceptibility to chronic diseases such as cancer and cardiovascular disease. The senescence-associated secretory phenotype is described, as well as the involvement of this phenomenon in the paracrine induction of senescence in otherwise healthy cells. Inflammaging is discussed in detail, along with the comorbidities associated with this process. A knowledge of these processes is required in order to consider possible targets for the application of senotherapeutic agents - interventions with the potential to modulate the senescence process, thus prolonging the healthy lifespan of the immune system and minimizing the secondary effects of immunosenescence.
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Zhou A, Lei Y, Tang L, Hu S, Yang M, Wu L, Yang S, Tang B. Gut Microbiota: the Emerging Link to Lung Homeostasis and Disease. J Bacteriol 2021; 203:e00454-20. [PMID: 33077630 PMCID: PMC7847545 DOI: 10.1128/jb.00454-20] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The gut microbiota plays a crucial role in the development of the immune system and confers benefits or disease susceptibility to the host. Emerging studies have indicated the gut microbiota could affect pulmonary health and disease through cross talk between the gut microbiota and the lungs. Gut microbiota dysbiosis could lead to acute or chronic lung disease, such as asthma, tuberculosis, and lung cancer. In addition, the composition of the gut microbiota may be associated with different lung diseases, the prevalence of which also varies by age. Modulation of the gut microbiota through short-chain fatty acids, probiotics, and micronutrients may present potential therapeutic strategies to protect against lung diseases. In this review, we will provide an overview of the cross-talk between the gut microbiota and the lungs, as well as elucidate the underlying pathogenesis and/or potential therapeutic strategies of some lung diseases from the point of view of the gut microbiota.
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Affiliation(s)
- An Zhou
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Yuanyuan Lei
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Li Tang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Shiping Hu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Min Yang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Lingyi Wu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Bo Tang
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
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Zou J, Guo S, Xiong MT, Xu Y, Shao J, Tong Z, Zhang P, Pan L, Peng A, Li X. Ageing as key factor for distant metastasis patterns and prognosis in patients with extensive-stage Small Cell Lung Cancer. J Cancer 2021; 12:1575-1582. [PMID: 33613744 PMCID: PMC7890308 DOI: 10.7150/jca.49681] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 12/23/2020] [Indexed: 11/17/2022] Open
Abstract
Background: Small cell lung cancer (SCLC) represents about 13% of lung cancer cases, which is highly invasive and has a high mortality rate, with the 5-year overall survival (OS) rate being only 6.3%. Age at diagnosis of advanced SCLC is much older, but studies describing the ageing factor for distant metastasis patterns and prognosis of extensive-stage SCLC (ES-SCLC) are limited. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified 18,682 patients with ES-SCLC (9,089 women and 9,053 men) who had complete clinical information between 2008 and 2015. Patients were classified into three groups (older group: ≥80 yrs, middle-aged group: 60-79 yrs, and younger group: ≤59 yrs). The role of different age at diagnosis of ES-SCLC (especially older group) in metastasis patterns was investigated, and OS and cancer-specific survival (CSS) of different age groups of metastatic ES-SCLC was assessed. Results: The most metastasis of ES-SCLC patients in the three groups was multiorgan metastases (MOM) metastasis (71.2%, 70.3% and 66.3%, respectively), the most single organ metastasis in the younger group was the lung (3.3%), the middle-aged group and the older group were the brain (3.5%, 3.1%, respectively). The analysis revealed that older patients were less likely to have MOM, but more likely to have all organs metastases than other two groups (p<0.001). Older group had the worst OS (p<0.001) and CSS (p<0.001). Furthermore, Radiotherapy and chemotherapy can improve survival (p<0.001), but the rate of radiotherapy and chemotherapy in older patients is lower than that in middle-aged and younger patients (50.4% vs 38.6% vs 20.7%, p<0.05). Compared with other two group, older group (odds ratios, ORs) for lung, all organ metastases, and MOM were 0.43 (95% CI 0.27-0.67), 1.77 (95% CI 1.55-2.03), 0.68 (95% CI 0.6-0.77), respectively. Conclusion: The mortality risk is highest with MOM and all organs metastasis followed by brain, lung, bone and liver metastases in elderly ES-SCLC patients. These results will be helpful for pre-treatment evaluation regarding the prognosis of ES-SCLC patients.
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Affiliation(s)
- Junyong Zou
- Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.,Department of Respiratory Medicine, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China.,Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences,Ningbo 315010, China
| | - Shijie Guo
- Department of Neurology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Meng Ting Xiong
- Department of Tuberculosis, Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Yingchun Xu
- Tongji University School of Medicine, Shanghai 200092, China
| | - Jiale Shao
- Department of Respiratory Medicine, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China
| | - Zhongkai Tong
- Department of Respiratory Medicine, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China
| | - Peng Zhang
- Department of Cardio-Thoracic Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai200072, China
| | - Long Pan
- Department of Interventional and Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai200072, China
| | - Aimei Peng
- Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Xuan Li
- Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
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Age-Related Immune Profile of the T Cell Receptor Repertoire, Thymic Recent Output Function, and miRNAs. BIOMED RESEARCH INTERNATIONAL 2020; 2020:5910823. [PMID: 33344643 PMCID: PMC7732372 DOI: 10.1155/2020/5910823] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 11/13/2020] [Accepted: 11/24/2020] [Indexed: 11/18/2022]
Abstract
Background T cell immunity plays a central role in the body's defense system, including maintaining homeostasis and preventing tumorigenesis and viral infection. Immune system functions degenerate with age, leading to immune senescence. Physiologically, immune senescence is characterized by a decrease in T cell receptor diversity, naive T cell deficiency, and alterations in T cell immune-related miRNAs. However, little is known about the characteristics of T cell immunosenescence in Chinese individuals. Results A significant decrease in the miR-17, miR-92a, and miR-181a levels in PBMCs was detected with age. The miR-92a and miR-181a levels were upregulated in CBMCs when comparing healthy individuals to group I (0~9 years), whereas miR-17 was downregulated. The sjTREC level in PBMCs was negatively correlated with age, and a sharp decrease in sjTRECs was found between groups I and II (10~19 years). Twenty-four TCR Vβ subfamilies could be detected in most samples, and most displayed polyclonality, while skewed expression of the Vβ subfamilies as well as an increased oligoclonal tendency was found with age. Similarly, the frequencies of the TCR Vγ and Vδ subfamilies decreased with age, and the alteration in clonality appeared to be stable at different ages. Conclusion We made the novel observation of T cell immunosenescence with age in Chinese individuals, which may provide information for immune targets to enhance the T cell immune response in immunotherapy settings for elderly patients.
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Kundu D, Kennedy L, Meadows V, Baiocchi L, Alpini G, Francis H. The Dynamic Interplay Between Mast Cells, Aging/Cellular Senescence, and Liver Disease. Gene Expr 2020; 20:77-88. [PMID: 32727636 PMCID: PMC7650013 DOI: 10.3727/105221620x15960509906371] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Mast cells are key players in acute immune responses that are evidenced by degranulation leading to a heightened allergic response. Activation of mast cells can trigger a number of different pathways contributing to metabolic conditions and disease progression. Aging results in irreversible physiological changes affecting all organs, including the liver. The liver undergoes senescence, changes in protein expression, and cell signaling phenotypes during aging, which regulate disease progression. Cellular senescence contributes to the age-related changes. Unsurprisingly, mast cells also undergo age-related changes in number, localization, and activation throughout their lifetime, which adversely affects the etiology and progression of many physiological conditions including liver diseases. In this review, we discuss the role of mast cells during aging, including features of aging (e.g., senescence) in the context of biliary diseases such as primary biliary cholangitis and primary sclerosing cholangitis and nonalcoholic fatty liver disease.
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Affiliation(s)
- Debjyoti Kundu
- *Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Lindsey Kennedy
- *Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Vik Meadows
- *Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Leonardo Baiocchi
- †Department of Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Gianfranco Alpini
- *Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- ‡Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA
| | - Heather Francis
- *Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- ‡Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA
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McCarthy M, Raval AP. The peri-menopause in a woman's life: a systemic inflammatory phase that enables later neurodegenerative disease. J Neuroinflammation 2020; 17:317. [PMID: 33097048 PMCID: PMC7585188 DOI: 10.1186/s12974-020-01998-9] [Citation(s) in RCA: 113] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 10/14/2020] [Indexed: 02/08/2023] Open
Abstract
The peri-menopause or menopausal transition—the time period that surrounds the final years of a woman’s reproductive life—is associated with profound reproductive and hormonal changes in a woman’s body and exponentially increases a woman’s risk of cerebral ischemia and Alzheimer’s disease. Although our understanding of the exact timeline or definition of peri-menopause is limited, it is clear that there are two stages to the peri-menopause. These are the early menopausal transition, where menstrual cycles are mostly regular, with relatively few interruptions, and the late transition, where amenorrhea becomes more prolonged and lasts for at least 60 days, up to the final menstrual period. Emerging evidence is showing that peri-menopause is pro-inflammatory and disrupts estrogen-regulated neurological systems. Estrogen is a master regulator that functions through a network of estrogen receptors subtypes alpha (ER-α) and beta (ER-β). Estrogen receptor-beta has been shown to regulate a key component of the innate immune response known as the inflammasome, and it also is involved in regulation of neuronal mitochondrial function. This review will present an overview of the menopausal transition as an inflammatory event, with associated systemic and central nervous system inflammation, plus regulation of the innate immune response by ER-β-mediated mechanisms.
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Affiliation(s)
- Micheline McCarthy
- Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Ami P Raval
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Leonard M. Miller School of Medicine, University of Miami, 1420 NW 9th Avenue, Neurology Research Building, Room # 203H, Miami, FL, 33136, USA. .,Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
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Chiu YL, Tsai WC, Hung RW, Chen IY, Shu KH, Pan SY, Yang FJ, Ting TT, Jiang JY, Peng YS, Chuang YF. Emergence of T cell immunosenescence in diabetic chronic kidney disease. IMMUNITY & AGEING 2020; 17:31. [PMID: 33088331 PMCID: PMC7574244 DOI: 10.1186/s12979-020-00200-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 09/17/2020] [Indexed: 02/07/2023]
Abstract
Background Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease (ESRD) in developed countries. It is known that patients with ESRD and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear. Method 523 adult patients with type 2 diabetes were recruited for this study. Demographic data and clinical information were obtained from medical chart review. Immunosenescence, or aging of the immune system was assessed by staining freshly-obtained peripheral blood with immunophenotyping panels and analyzing cells using multicolor flow cytometry. Result Consistent with previously observed in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. When compared to diabetic patients with preserved renal function (estimated glomerular filtration rate > 60 ml/min), patients with impaired renal function exhibit a significant decrease of total CD3+ and CD4+ T cells, but not CD8+ T cell and monocyte numbers. Immunosenescence was observed in patients with CKD stage 3 and in patients with more severe renal failure, especially of CD8+ T cells. However, immunosenescence was not associated with level of proteinuria level or glucose control. In age, sex and glucose level-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28-, CD127-, and CD57+ cells among CD8+ T cells when compared to patients with preserved renal function. In contrast, no change was detected in monocyte subpopulations as renal function declined. In addition, higher body mass index (BMI) is associated with enhanced immunosenescence irrespective of CKD status. Conclusion The extent of immunosenescence is not significantly associated with proteinuria or glucose control in type 2 diabetic patients. T cells, especially the CD8+ subsets, exhibit aggravated characteristics of immunosenescence during renal function decline as early as stage 3 CKD. In addition, inflammation increases since stage 3 CKD and higher BMI drives the accumulation of CD8+CD57+ T cells. Our study indicates that therapeutic approaches such as weight loss may be used to prevent the emergence of immunosenescence in diabetes before stage 3 CKD.
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Affiliation(s)
- Yen-Ling Chiu
- Graduate Program in Biomedical Informatics, Department of Computer Science and Engineering, College of Informatics, Yuan Ze University, Taoyuan, Taiwan.,Division of Nephrology, Department of Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wan-Chuan Tsai
- Division of Nephrology, Department of Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,Center for General Education, Lee-Ming Institute of Technology, New Taipei City, Taiwan
| | - Ruo-Wei Hung
- Division of Nephrology, Department of Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - I-Yu Chen
- Division of Nephrology, Department of Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Kai-Hsiang Shu
- Division of Nephrology, Department of Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Szu-Yu Pan
- Division of Nephrology, Department of Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Feng-Jung Yang
- Department of Medicine, National Taiwan University Hospital Yun Lin Branch, Douliu, Taiwan
| | - Te-Tien Ting
- School of Big Data Management, Soochow University, Taipei, Taiwan
| | - Ju-Ying Jiang
- Division of Endocrinology and Metabolism, Department of Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Yu-Sen Peng
- Division of Nephrology, Department of Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.,Department of Applied Cosmetology, Lee-Ming Institute of Technology, New Taipei City, Taiwan.,Department of Healthcare Administration, Oriental Institute of Technology, New Taipei City, Taiwan
| | - Yi-Fang Chuang
- Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan
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Abstract
PURPOSE OF REVIEW Different factors contribute to the decreased overall long-term survival in treated people living with HIV (PLWH). This paper will review the state of physical frailty which limits successful aging in PLWH. RECENT FINDINGS Identifiable events on the continuum from clinical normality to heightened risk of adverse health outcomes contribute to frailty. These center on chronic inflammation leading to destabilization of autoregulated physiologic systems challenged by environmental and biologic challenges. Frailty assessment can inform the profile of aging PLWH at increased risk of common age-related disorders and geriatric syndromes. Biologic and psychosocial risk factors promoting progression to and reversion from a dynamic state of frailty are being investigated, allowing for preventative interventions to be considered. Insights gained from studying frail PLWH will help adapt an interdisciplinary geriatric model of health care for selected PLWH. This will improve the health and well-being of aging PLWH.
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Affiliation(s)
- Julian Falutz
- Division of Geriatrics, Director, Comprehensive HIV and Aging Initiative, McGill University Health Centre, Montreal, Quebec, Canada.
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Santoro A, Zhao J, Wu L, Carru C, Biagi E, Franceschi C. Microbiomes other than the gut: inflammaging and age-related diseases. Semin Immunopathol 2020; 42:589-605. [PMID: 32997224 PMCID: PMC7666274 DOI: 10.1007/s00281-020-00814-z] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 07/28/2020] [Indexed: 12/14/2022]
Abstract
During the course of evolution, bacteria have developed an intimate relationship with humans colonizing specific body sites at the interface with the body exterior and invaginations such as nose, mouth, lung, gut, vagina, genito-urinary tract, and skin and thus constituting an integrated meta-organism. The final result has been a mutual adaptation and functional integration which confers significant advantages to humans and bacteria. The immune system of the host co-evolved with the microbiota to develop complex mechanisms to recognize and destroy invading microbes, while preserving its own bacteria. Composition and diversity of the microbiota change according to development and aging and contribute to humans' health and fitness by modulating the immune system response and inflammaging and vice versa. In the last decades, we experienced an explosion of studies on the role of gut microbiota in aging, age-related diseases, and longevity; however, less reports are present on the role of the microbiota at different body sites. In this review, we describe the key steps of the co-evolution between Homo sapiens and microbiome and how this adaptation can impact on immunosenescence and inflammaging. We briefly summarized the role of gut microbiota in aging and longevity while bringing out the involvement of the other microbiota.
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Affiliation(s)
- Aurelia Santoro
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy.
| | - Jiangchao Zhao
- Department of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, AR, 72703, USA
| | - Lu Wu
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
| | - Ciriaco Carru
- Department of Biomedical Sciences, University Hospital (AOU) - University of Sassari, Sassari, Italy
| | - Elena Biagi
- Department of Pharmacy and Biotechnology (FABIT), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Claudio Franceschi
- Laboratory of Systems Medicine of Healthy Aging and Department of Applied Mathematics, Lobachevsky University, Nizhny Novgorod, Russia
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Sharma R, Padwad Y. Perspectives of the potential implications of polyphenols in influencing the interrelationship between oxi-inflammatory stress, cellular senescence and immunosenescence during aging. Trends Food Sci Technol 2020. [DOI: 10.1016/j.tifs.2020.02.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Froy H, Sparks AM, Watt K, Sinclair R, Bach F, Pilkington JG, Pemberton JM, McNeilly TN, Nussey DH. Senescence in immunity against helminth parasites predicts adult mortality in a wild mammal. Science 2020; 365:1296-1298. [PMID: 31604239 DOI: 10.1126/science.aaw5822] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 07/30/2019] [Indexed: 12/14/2022]
Abstract
Our understanding of the deterioration in immune function in old age-immunosenescence-derives principally from studies of modern human populations and laboratory animals. The generality and significance of this process for systems experiencing complex, natural infections and environmental challenges are unknown. Here, we show that late-life declines in an important immune marker of resistance to helminth parasites in wild Soay sheep predict overwinter mortality. We found senescence in circulating antibody levels against a highly prevalent nematode worm, which was associated with reduced adult survival probability, independent of changes in body weight. These findings establish a role for immunosenescence in the ecology and evolution of natural populations.
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Affiliation(s)
- H Froy
- Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK. .,Centre for Biodiversity Dynamics, Norwegian University of Science and Technology, Trondheim, Norway
| | - A M Sparks
- Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK.,School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
| | - K Watt
- Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK
| | - R Sinclair
- Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK
| | - F Bach
- Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK
| | - J G Pilkington
- Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK
| | - J M Pemberton
- Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK
| | - T N McNeilly
- Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, UK
| | - D H Nussey
- Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK
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Sokolenko VL, Sokolenko SV. Manifestations of allostatic load in residents of radiation contaminated areas aged 18–24 years. REGULATORY MECHANISMS IN BIOSYSTEMS 2019. [DOI: 10.15421/021963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
We studied the features of allostatic load (AL) in 100 students aged 18–24 years old who, from birth to adulthood, lived in the territories assigned to the IV radiation zone after the Chornobyl accident (density of soil contamination by isotopes 137Cs 3.7–18.5∙104 Bq/m2) and underwent prolonged exposure to small doses of ionizing radiation. The examined students did not have any clinical signs of the immune-neuroendocrine system dysfunction. 50 people had signs of vegetative-vascular dystonia syndrome (VVD), 48 had signs of moderate hyperthyroidism and 21 had signs of moderate hypothyroidism. During the examination session, as a factor of additional psycho-emotional load, in 66 of the examined the immunoregulatory index CD4+/CD8+ went below the lower limit of the homeostatic norm, in 62 of the examined low density lipoprotein cholesterol (LDL-C) exceeded the upper level. The relative risk (RR) and attributable risk (AR) of the participation of potential secondary factors of allostatic load formation in CD4+/CD8+ immunoregulatory index going below the lower limit were calculated. The presence of statistically significant relative risk of participation in the formation of suppression of the index CD4+/CD8+: the state of hyperthyroidism, state of hypothyroidism, vegetative-vascular dystonia syndrome, higher than normal LDL-C. When the examined students combined the signs of hyperthyroidism, vegetative-vascular dystonia syndrome and higher level of LDL-C; with combination of signs of hypothyroidism, vegetative-vascular dystonia syndrome and higher level of LDL-C. The attributable risk in all cases exceeded 0.10, which confirmed the importance of some of these factors and their complexes in the formation of the effect of reduced immunoregulatory index. The CD4+/CD8+ index can be considered an important biomarker of AL and premature age-related changes in the immune system in residents of radiation-contaminated areas. The risk of AL formation in the case of occurrence of a complex of mediated secondary biomarkers (vegetative-vascular dystonia syndrome, thyroid dysfunction, hypercholesterolemia) is higher compared to their individual significance.
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Zhang G, Wang Y, Luo H, Qiu W, Zhang H, Hu L, Wang Y, Dong G, Guo G. The Association Between Inflammaging and Age-Related Changes in the Ruminal and Fecal Microbiota Among Lactating Holstein Cows. Front Microbiol 2019; 10:1803. [PMID: 31447814 PMCID: PMC6696898 DOI: 10.3389/fmicb.2019.01803] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Accepted: 07/22/2019] [Indexed: 12/31/2022] Open
Abstract
Inflammaging is well understood in the study of humans; however, it is rarely reported for dairy cows. To understand the changing pattern of the gut microbiota, inflammatory status and milk production performance during the aging process in cows, we grouped 180 cows according to their lactation period: L1 (n = 60, 1st lactation), L3 (n = 60, 3rd lactation), and L5+ (n = 60, at least 5th lactation) and analyzed their milk components and daily milk yields to evaluate the changing pattern of milk production. The microbiota was analyzed using high-throughput sequencing of amplicons of 16S rRNA, which also allowed us to predict the functions of microbes and then study the changing pattern of the ruminal and fecal microbiota. Serum cytokines, including TNF-α, IL-6, IL-10, and TGF-β were measured to study the progress of inflammaging in the cows. We found that old cows (L5+) suffered from a long-term and low-level chronic inflammation, as indicated by significantly higher levels of inflammatory cytokines IL-10, TNF-α, and TGF-β in the L5+ group (p < 0.001). We also observed a significant decrease in daily milk yield and milk lactose, as well as a significant increase in somatic cell score, among the cows in the L5+ group. For the gut microbiota, most of the genera belonging to Prevotellaceae and Lachnospiraceae, which had a higher abundance among cows of both the L1 and L3 groups (LEfSe, LDA > 2), showed a similar change pattern during the aging process, both in the rumen and in feces, and across the six farms. Beneficial bacteria, like Bacteroidaceae, Eubacterium, and Bifidobacterium, displayed lower abundance in the feces of the L5+ group (LEfSe, LDA > 2). Reconstruction of the fecal bacteria community indicated transformation of the fermenting pattern of older cows' (L5+) feces microbiota, with increased functions related the protein metabolism and fewer functions related to carbohydrate and lipid metabolism compared with those in L1 (p < 0.05). Finally, the connections among these changing patterns were revealed using redundancy analysis and network analysis. The results support the hypothesis of prolonging a cows' productive life and improve dairy cow milk productive performances by manipulating the gut microbiota.
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Affiliation(s)
- Guoxing Zhang
- Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
- Shenzhen Weishengtai Technology Co., Ltd., Shenzhen, China
| | - Yachun Wang
- Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Hanpeng Luo
- Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Wenqing Qiu
- Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Hailiang Zhang
- Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Lirong Hu
- College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, China
| | - Yajing Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Ganghui Dong
- Beijing Sunlon Livestock Development Co., Ltd., Beijing, China
| | - Gang Guo
- Beijing Sunlon Livestock Development Co., Ltd., Beijing, China
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43
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Peters A, Delhey K, Nakagawa S, Aulsebrook A, Verhulst S. Immunosenescence in wild animals: meta‐analysis and outlook. Ecol Lett 2019; 22:1709-1722. [DOI: 10.1111/ele.13343] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 05/30/2019] [Accepted: 06/18/2019] [Indexed: 12/15/2022]
Affiliation(s)
- Anne Peters
- School of Biological Sciences Monash University Clayton Vic. 3800 Australia
| | - Kaspar Delhey
- School of Biological Sciences Monash University Clayton Vic. 3800 Australia
| | - Shinichi Nakagawa
- School of Biological, Earth and Environmental Sciences University of New South Wales Sydney NSW 2052 Australia
| | - Anne Aulsebrook
- School of Biological Sciences Monash University Clayton Vic. 3800 Australia
- School of BioSciences University of Melbourne Parkville Vic. 3010 Australia
| | - Simon Verhulst
- Groningen Institute for Evolutionary Life Sciences University of Groningen 9747 AGGroningen The Netherlands
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44
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Rožman P. How Could We Slow or Reverse the Human Aging Process and Extend the Healthy Life Span with Heterochronous Autologous Hematopoietic Stem Cell Transplantation. Rejuvenation Res 2019; 23:159-170. [PMID: 31203790 DOI: 10.1089/rej.2018.2164] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The senescence of the immune system contributes considerably to the age-related diseases that are the main causes of death after the age of 65. In this study, we present an appealing option for the prevention of immune senescence and slowing or reversing the aging process, which can be achieved by heterochronous autologous hematopoietic stem cell transplantation (haHSCT), where healthy autologous bone marrow stem cells are collected from donors while young, cryopreserved and stored for a long period, and reinfused at a later time when indicated. After reinfusion and homing, these young HSCs could participate in normal hemato- and immunopoiesis and improve several immune functions by expanding the immune- as well as hematopoietic cell repertoire. Several animal studies have already confirmed the feasibility of this procedure, which extended the longevity of the treated animals. If translated to human medicine, haHSCT could prevent or mitigate age-related immune defects and extend the healthy life span. In this review, we describe the concept of haHSCT, recent studies that confirm its feasibility, and discuss the further research needed to translate this heterochronous methodology.
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Affiliation(s)
- Primož Rožman
- Immunohaematology Department, Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia
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45
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Muntasell A, Servitja S, Cabo M, Bermejo B, Pérez-Buira S, Rojo F, Costa-García M, Arpí O, Moraru M, Serrano L, Tusquets I, Martínez MT, Heredia G, Vera A, Martínez-García M, Soria L, Comerma L, Santana-Hernández S, Eroles P, Rovira A, Vilches C, Lluch A, Albanell J, López-Botet M. High Numbers of Circulating CD57 + NK Cells Associate with Resistance to HER2-Specific Therapeutic Antibodies in HER2 + Primary Breast Cancer. Cancer Immunol Res 2019; 7:1280-1292. [PMID: 31189644 DOI: 10.1158/2326-6066.cir-18-0896] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 04/11/2019] [Accepted: 06/10/2019] [Indexed: 11/16/2022]
Abstract
Natural killer (NK) cells can orchestrate effective antitumor immunity. The presence of tumor-infiltrating NK cells in diagnostic biopsies predicts pathologic complete response (pCR) to HER2-specific therapeutic antibodies in patients with primary breast cancer. Here, we analyzed whether diversity in circulating NK cells might influence tumor infiltration and HER2-specific therapeutic antibody efficacy. We found that numbers of circulating CD57+ NK cells inversely correlated with pCR to HER2-specific antibody treatment in patients with primary breast cancer independently of age, traditional clinicopathologic factors, and CD16A 158F/V genotype. This association was uncoupled from the expression of other NK-cell receptors, the presence of adaptive NK cells, or changes in major T-cell subsets, reminiscent of cytomegalovirus-induced immunomodulation. NK-cell activation against trastuzumab-coated HER2+ breast cancer cells was comparable in patients with high and low proportions of CD57+ NK cells. However, circulating CD57+ NK cells displayed decreased CXCR3 expression and CD16A-induced IL2-dependent proliferation in vitro Presence of CD57+ NK cells was reduced in breast tumor-associated infiltrates as compared with paired peripheral blood samples, suggesting deficient homing, proliferation, and/or survival of NK cells in the tumor niche. Indeed, numbers of circulating CD57+ were inversely related to tumor-infiltrating NK-cell numbers. Our data reveal that NK-cell differentiation influences their antitumor potential and that CD57+ NK cells may be a biomarker useful for tailoring HER2 antibody-based therapeutic strategies in breast cancer.
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Affiliation(s)
- Aura Muntasell
- Immunity and Infection, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.
| | - Sònia Servitja
- Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.,Department of Medical Oncology, Hospital del Mar-CIBERONC, Barcelona, Spain
| | - Mariona Cabo
- Immunity and Infection, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain
| | - Begoña Bermejo
- Department of Oncology, Hospital Clinico de Valencia-CIBERONC, Valencia, Spain
| | - Sandra Pérez-Buira
- Department of Pathology, IIS "Fundacion Jimenez Diaz University Hospital," Madrid, Spain
| | - Federico Rojo
- Department of Pathology, IIS "Fundacion Jimenez Diaz University Hospital," Madrid, Spain
| | | | - Oriol Arpí
- Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain
| | - Manuela Moraru
- HLA-Immunogenetics Department, Instituto Hospital Universitario Puerta de Hierro, Majadahonda, Spain
| | - Laia Serrano
- Department of Pathology, Hospital del Mar, Barcelona, Spain
| | - Ignasi Tusquets
- Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.,Department of Medical Oncology, Hospital del Mar-CIBERONC, Barcelona, Spain.,Universitat Pompeu Fabra, Barcelona, Spain
| | | | | | - Andrea Vera
- Immunity and Infection, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain
| | - María Martínez-García
- Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.,Department of Medical Oncology, Hospital del Mar-CIBERONC, Barcelona, Spain
| | - Laura Soria
- Immunity and Infection, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain
| | - Laura Comerma
- Department of Pathology, Hospital del Mar, Barcelona, Spain
| | - Sara Santana-Hernández
- Immunity and Infection, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain
| | - Pilar Eroles
- Department of Oncology, Hospital Clinico de Valencia-CIBERONC, Valencia, Spain.,Biomedical Research Institute, INCLIVA, Valencia, Spain
| | - Ana Rovira
- Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.,Department of Medical Oncology, Hospital del Mar-CIBERONC, Barcelona, Spain
| | - Carlos Vilches
- HLA-Immunogenetics Department, Instituto Hospital Universitario Puerta de Hierro, Majadahonda, Spain
| | - Ana Lluch
- Department of Oncology, Hospital Clinico de Valencia-CIBERONC, Valencia, Spain.,Biomedical Research Institute, INCLIVA, Valencia, Spain.,Universitat de Valencia, Valencia, Spain
| | - Joan Albanell
- Cancer Research Program, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain. .,Department of Medical Oncology, Hospital del Mar-CIBERONC, Barcelona, Spain.,Universitat Pompeu Fabra, Barcelona, Spain
| | - Miguel López-Botet
- Immunity and Infection, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.,Universitat Pompeu Fabra, Barcelona, Spain
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46
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Müller L, Di Benedetto S, Pawelec G. The Immune System and Its Dysregulation with Aging. Subcell Biochem 2019; 91:21-43. [PMID: 30888648 DOI: 10.1007/978-981-13-3681-2_2] [Citation(s) in RCA: 146] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Aging leads to numerous changes that affect all physiological systems of the body including the immune system, causing greater susceptibility to infectious disease and contributing to the cardiovascular, metabolic, autoimmune, and neurodegenerative diseases of aging. The immune system is itself also influenced by age-associated changes occurring in such physiological systems as the endocrine, nervous, digestive, cardio-vascular and muscle-skeletal systems. This chapter describes the multidimensional effects of aging on the most important components of the immune system. It considers the age-related changes in immune cells and molecules of innate and adaptive immunity and consequent impairments in their ability to communicate with each other and with their aged environment. The contribution of age-related dysregulation of hematopoiesis, required for continuous replenishment of immune cells throughout life, is discussed in this context, as is the developmentally-programmed phenomenon of thymic involution that limits the output of naïve T cells and markedly contributes to differences between younger and older people in the distribution of peripheral blood T-cell types. How all these changes may contribute to low-grade inflammation, sometimes dubbed "inflammaging", is considered. Due to findings implicating elevated inflammatory immuno-mediators in age-associated chronic autoimmune and neurodegenerative processes, evidence for their possible contribution to neuroinflammation is reviewed.
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Affiliation(s)
- Ludmila Müller
- Max Planck Institute for Human Development, Berlin, Germany.
| | - Svetlana Di Benedetto
- Max Planck Institute for Human Development, Berlin, Germany.,Center for Medical Research, University of Tübingen, Tübingen, Germany
| | - Graham Pawelec
- Center for Medical Research, University of Tübingen, Tübingen, Germany.,Health Sciences North Research Institute, Sudbury, ON, Canada
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47
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mTOR and Aging: An Old Fashioned Dress. Int J Mol Sci 2019; 20:ijms20112774. [PMID: 31174250 PMCID: PMC6600378 DOI: 10.3390/ijms20112774] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 06/03/2019] [Accepted: 06/04/2019] [Indexed: 12/12/2022] Open
Abstract
Aging is a physiologic/pathologic process characterized by a progressive impairment of cellular functions, supported by the alterations of several molecular pathways, leading to an increased cell susceptibility to injury. This deterioration is the primary risk factor for several major human pathologies. Numerous cellular processes, including genomic instability, telomere erosion, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, stem cell exhaustion, and altered intercellular signal transduction represent common denominators of aging in different organisms. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved nutrient sensing protein kinase that regulates growth and metabolism in all eukaryotic cells. Studies in flies, worms, yeast, and mice support the hypothesis that the mTOR signalling network plays a pivotal role in modulating aging. mTOR is emerging as the most robust mediator of the protective effects of various forms of dietary restriction, which has been shown to extend lifespan and slow the onset of age-related diseases across species. Herein we discuss the role of mTor signalling network in the development of classic age-related diseases, focused on cardiovascular system, immune response, and cancer.
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48
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Tangestani Fard M, Stough C. A Review and Hypothesized Model of the Mechanisms That Underpin the Relationship Between Inflammation and Cognition in the Elderly. Front Aging Neurosci 2019; 11:56. [PMID: 30930767 PMCID: PMC6425084 DOI: 10.3389/fnagi.2019.00056] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 02/26/2019] [Indexed: 12/13/2022] Open
Abstract
Age is associated with increased risk for several disorders including dementias, cardiovascular disease, atherosclerosis, obesity, and diabetes. Age is also associated with cognitive decline particularly in cognitive domains associated with memory and processing speed. With increasing life expectancies in many countries, the number of people experiencing age-associated cognitive impairment is increasing and therefore from both economic and social terms the amelioration or slowing of cognitive aging is an important target for future research. However, the biological causes of age associated cognitive decline are not yet, well understood. In the current review, we outline the role of inflammation in cognitive aging and describe the role of several inflammatory processes, including inflamm-aging, vascular inflammation, and neuroinflammation which have both direct effect on brain function and indirect effects on brain function via changes in cardiovascular function.
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Affiliation(s)
| | - Con Stough
- Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, VIC, Australia
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49
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Civljak R, Tot T, Falsey AR, Huljev E, Vranes J, Ljubin-Sternak S. Viral pathogens associated with acute respiratory illness in hospitalized adults and elderly from Zagreb, Croatia, 2016 to 2018. J Med Virol 2019; 91:1202-1209. [PMID: 30801727 PMCID: PMC7166480 DOI: 10.1002/jmv.25437] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 01/25/2019] [Accepted: 02/18/2019] [Indexed: 11/22/2022]
Abstract
Aims To investigate the viral etiology of acute respiratory infection (ARI) in hospitalized adults and elderly patients in Croatia, compare the prevalence of detected viruses, and to determine clinical characteristics and seasonal occurrence of investigated infections. Methods From January 2016 to June 2018, a total of 182 adult patients presented with symptoms of ARI and admitted to the hospital were tested for 15 respiratory viruses by multiplex reverse‐transcription polymerase chain reaction. Clinical data were collected by retrospective analysis of the patient's chart. Results A virus was identified in 106 (58.5%) of the patients. The most commonly detected virus was influenza virus (41.5%), followed by respiratory syncytial virus (13.8%), human metapneumovirus (13.0%), parainfluenza viruses (12.2%), rhinoviruses (11.4%), adenovirus and coronaviruses with equal frequencies (3.3%), and enterovirus (1.6%). The serum level of C‐reactive protein and white blood cell count were significantly lower in patients with respiratory viruses identified when compared with those in whom no virus was detected (P < 0.001 and
P = 0.007, respectively). There were no differences in clinical symptoms according to the type of the detected virus, except for more frequent illness exposure recall for influenza infection (
P = 0.010). Influenza, parainfluenza, and pneumoviruses were detected mostly in winter months, while rhinoviruses in autumn and spring. Conclusions In addition to influenza, pneumoviruses, rhinoviruses, and parainfluenza viruses play an important role in etiology of ARIs in adults. Fast and accurate laboratory diagnosis for respiratory viruses in routine practice is needed for clinicians optimally manage patients with ARI and potentially avoid the unnecessary use of antimicrobial drugs.
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Affiliation(s)
- Rok Civljak
- Department of Respiratory Tract Infections, Dr Fran Mihaljevic University Hospital for Infectious Diseases, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Tatjana Tot
- Department of Microbiology, General Hospital Karlovac, Karlovac, Croatia
| | - Ann R Falsey
- Department of Medicine, Rochester General Hospital and University of Rochester School of Medicine and Dentistry, Rochester, New York
| | - Eva Huljev
- Department of Respiratory Tract Infections, Dr Fran Mihaljevic University Hospital for Infectious Diseases, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Jasmina Vranes
- Department of Clinical Microbiology, Dr Andrija Stampar Teaching Institute of Public Health, Zagreb, Croatia.,Department of Medical Microbiology, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Suncanica Ljubin-Sternak
- Department of Clinical Microbiology, Dr Andrija Stampar Teaching Institute of Public Health, Zagreb, Croatia.,Department of Medical Microbiology, University of Zagreb School of Medicine, Zagreb, Croatia
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50
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Oxidative Stress and Nutraceuticals in the Modulation of the Immune Function: Current Knowledge in Animals of Veterinary Interest. Antioxidants (Basel) 2019; 8:antiox8010028. [PMID: 30669304 PMCID: PMC6356544 DOI: 10.3390/antiox8010028] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 01/11/2019] [Accepted: 01/15/2019] [Indexed: 12/20/2022] Open
Abstract
In the veterinary sector, many papers deal with the relationships between inflammation and oxidative stress. However, few studies investigate the mechanisms of action of oxidised molecules in the regulation of immune cells. Thus, authors often assume that these events, sometime leading to oxidative stress, are conserved among species. The aim of this review is to draw the state-of-the-art of the current knowledge about the role of oxidised molecules and dietary antioxidant compounds in the regulation of the immune cell functions and suggest some perspectives for future investigations in animals of veterinary interest.
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