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Li Q, Zhang H, Xiao N, Liang G, Lin Y, Yang X, Yang J, Qian Z, Fu Y, Zhang C, Liu A. Aging and Lifestyle Modifications for Preventing Aging-Related Diseases. FASEB J 2025; 39:e70575. [PMID: 40293686 DOI: 10.1096/fj.202402797rr] [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: 11/14/2024] [Revised: 04/13/2025] [Accepted: 04/18/2025] [Indexed: 04/30/2025]
Abstract
The pathogenesis of various chronic diseases is closely associated with aging. Aging of the cardiovascular system promotes the development of severe cardiovascular diseases with high mortality, including atherosclerosis, coronary heart disease, and myocardial infarction. Similarly, aging of the nervous system promotes the development of neurodegenerative diseases, such as Alzheimer's disease, which seriously impairs cognitive function. Aging of the musculoskeletal system is characterized by decreased function and mobility. The molecular basis of organ aging is cellular senescence, which involves multiple cellular and molecular mechanisms, such as impaired autophagy, metabolic imbalance, oxidative stress, and persistent inflammation. Given the ongoing demographic shift toward an aging society, strategies to delay or reduce the effects of aging have gained significance. Lifestyle modifications, such as exercise and calorie restriction, are now recognized for their anti-aging effects, their capacity to reduce modification, their potential to prolong lifespan, and their capacity to lower the risk of cardiovascular disease. This review elucidates the molecular mechanisms and application significance of various anti-aging approaches at the molecular level, based on research progress in aging. It aims to provide a reference for the prevention and treatment of age-related diseases in progressively aging societies.
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Affiliation(s)
- Qiao Li
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Heng Zhang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Nanyin Xiao
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Guangyu Liang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan Lin
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiao Yang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiankun Yang
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zonghao Qian
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yangguang Fu
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cuntai Zhang
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Anding Liu
- Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Xu W, Li XJ, Zhong YS, He JQ, Xie W, Kang YK, Ying HZ, Yu CH. Structural characterizations and antiaging activities of hydrolyzed low-molecular-weight polysaccharides from Polygoni Multiflori Radix Praeparata. Carbohydr Polym 2025; 356:123381. [PMID: 40049961 DOI: 10.1016/j.carbpol.2025.123381] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 02/03/2025] [Accepted: 02/11/2025] [Indexed: 05/13/2025]
Abstract
Natural polysaccharides as the primary active components derived from herbal medicine often face challenges due to their large molecular weights, varying chemical structures and poor bioavailability, which significantly restrict their bioactive mechanism investigation and clinical applications. To improve the bioavailability and clarify the antiaging mechanism of polysaccharides from Polygoni Multiflori Radix Praeparata, the high-molecular-weight polysaccharides (PRP) were hydrolyzed into two low-molecular-weight fractions (PRP1 and PRP2) by hydrogen peroxide-ascorbic acid method. The results of structural characterization showed that they were glucans with the molecular weights of 13.43 kDa and 5.97 kDa, respectively. Compared with PRP and PRP1, PRP2 exhibited the most potent antiaging activity in D-galactose-treated T lymphocytes, attributed to its shorter chain length and lower molecular weight. Furthermore, oral administration with PRP2 not only decreased the levels of senescence-associated secretory phenotype (SASP)-related inflammatory cytokines, elevated the counts of T cells, NK cells, and macrophages in the blood, but also reduced the expressions of p16 and p21 proteins in spleen tissues of naturally aged C57BL/6J mice and two fast-aging (ERCC2+/- and TERT-/-) mice. Mechanistically, PRP2 competitively bound with Keap1 and subsequently activated Nrf2/HO-1 pathway. Therefore, PRP2 could be explored as a potential candidate for treatment of age-related diseases and overall aging.
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Affiliation(s)
- Wei Xu
- College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China; Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, Hangzhou 310053, China
| | - Xue-Jian Li
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou 310013, China; Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310018, China
| | - Yu-Sen Zhong
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou 310013, China
| | - Jia-Qi He
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
| | - Wei Xie
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou 310013, China; Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310018, China
| | - You-Kun Kang
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou 310013, China
| | - Hua-Zhong Ying
- Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou 310013, China
| | - Chen-Huan Yu
- Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310018, China.
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3
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Varghese N, Szabo L, Cader MZ, Lejri I, Grimm A, Eckert A. Tracing mitochondrial marks of neuronal aging in iPSCs-derived neurons and directly converted neurons. Commun Biol 2025; 8:723. [PMID: 40346193 PMCID: PMC12064796 DOI: 10.1038/s42003-025-08152-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 05/01/2025] [Indexed: 05/11/2025] Open
Abstract
This study aims to determine if neurons derived from induced pluripotent stem cells (iPSCsNs) and directly converted neurons (iNs) from the same source cells exhibit changes in mitochondrial properties related to aging. This research addresses the uncertainty around whether aged iPSCsNs retain aging-associated mitochondrial impairments upon transitioning through pluripotency while direct conversion maintains these impairments. We observe that both aged models exhibit characteristics of aging, such as decreased ATP, mitochondrial membrane potential, respiration, NAD+/NADH ratio, and increased radicals and mitochondrial mass. In addition, both neuronal models show a fragmented mitochondrial network. However, aged iPSCsNs do not exhibit a metabolic shift towards glycolysis, unlike aged iNs. Furthermore, mRNA expression differed significantly between aged iPSCsNs and aged iNs. The study concludes that aged iPSCsNs may differ in transcriptomics and the aging-associated glycolytic shift but can be a valuable tool for studying specific feature of mitochondrial neuronal aging in vitro alongside aged iNs.
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Affiliation(s)
- Nimmy Varghese
- Research Cluster Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland
- Neurobiology Lab for Brain Aging and Mental Health, University Psychiatric Clinics Basel, Basel, Switzerland
- Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA
| | - Leonora Szabo
- Research Cluster Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland
- Neurobiology Lab for Brain Aging and Mental Health, University Psychiatric Clinics Basel, Basel, Switzerland
| | - M Zameel Cader
- Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK
| | - Imane Lejri
- Research Cluster Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland
- Neurobiology Lab for Brain Aging and Mental Health, University Psychiatric Clinics Basel, Basel, Switzerland
| | - Amandine Grimm
- Research Cluster Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland
- Neurobiology Lab for Brain Aging and Mental Health, University Psychiatric Clinics Basel, Basel, Switzerland
- Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Anne Eckert
- Research Cluster Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland.
- Neurobiology Lab for Brain Aging and Mental Health, University Psychiatric Clinics Basel, Basel, Switzerland.
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Xiong J, Guo Q, Luo X. Cellular senescence in age-related musculoskeletal diseases. Front Med 2025:10.1007/s11684-025-1125-7. [PMID: 40314896 DOI: 10.1007/s11684-025-1125-7] [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: 07/30/2024] [Accepted: 12/16/2024] [Indexed: 05/03/2025]
Abstract
Aging is typically associated with decreased musculoskeletal function, leading to reduced mobility and increased frailty. As a hallmark of aging, cellular senescence plays a crucial role in various age-related musculoskeletal diseases, including osteoporosis, osteoarthritis, intervertebral disc degeneration, and sarcopenia. The detrimental effects of senescence are primarily due to impaired regenerative capacity of stem cells and the pro-inflammatory environment created by accumulated senescent cells. The secreted senescence-associated secretory phenotype (SASP) can induce senescence in neighboring cells, further amplifying senescent signals. Although the removal of senescent cells and the suppression of SASP factors have shown promise in alleviating disease progression and restoring musculoskeletal health in mouse models, clinical trials have yet to demonstrate significant efficacy. This review summarizes the mechanisms of cellular senescence in age-related musculoskeletal diseases and discusses potential therapeutic strategies targeting cellular senescence.
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Affiliation(s)
- Jinming Xiong
- Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, China
| | - Qiaoyue Guo
- Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, China.
| | - Xianghang Luo
- Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, China.
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Na D, Zhang Z, Meng M, Li M, Gao J, Kong J, Zhang G, Guo Y. Energy Metabolism and Brain Aging: Strategies to Delay Neuronal Degeneration. Cell Mol Neurobiol 2025; 45:38. [PMID: 40259102 PMCID: PMC12011708 DOI: 10.1007/s10571-025-01555-z] [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: 01/12/2025] [Accepted: 04/09/2025] [Indexed: 04/23/2025]
Abstract
Aging is characterized by a gradual decline in physiological functions, with brain aging being a major risk factor for numerous neurodegenerative diseases. Given the brain's high energy demands, maintaining an adequate ATP supply is crucial for its proper function. However, with advancing age, mitochondria dysfunction and a deteriorating energy metabolism lead to reduced overall energy production and impaired mitochondrial quality control (MQC). As a result, promoting healthy aging has become a key focus in contemporary research. This review examines the relationship between energy metabolism and brain aging, highlighting the connection between MQC and energy metabolism, and proposes strategies to delay brain aging by targeting energy metabolism.
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Affiliation(s)
- Donghui Na
- Department of Forensic Medicine, Hebei North University, Zhangjiakou, Hebei, China
| | - Zechen Zhang
- Mudi Meng Honors College, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Meng Meng
- Department of Forensic Medicine, Hebei North University, Zhangjiakou, Hebei, China
| | - Meiyu Li
- Department of Forensic Medicine, Hebei North University, Zhangjiakou, Hebei, China
- Department of Pathology, Hebei North University, Zhangjiakou, Hebei, China
| | - Junyan Gao
- Department of Forensic Medicine, Hebei North University, Zhangjiakou, Hebei, China
| | - Jiming Kong
- Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada.
| | - Guohui Zhang
- Department of Forensic Medicine, Hebei North University, Zhangjiakou, Hebei, China.
| | - Ying Guo
- Department of Forensic Medicine, Hebei North University, Zhangjiakou, Hebei, China.
- Department of Pathology, Hebei North University, Zhangjiakou, Hebei, China.
- Hebei Key Laboratory of Neuropharmacology, Hebei North University, Zhangjiakou, Hebei, China.
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Yao YQ, Cao QY, Li Z. Delaying liver aging: Analysis of structural and functional alterations. World J Gastroenterol 2025; 31:103773. [PMID: 40309235 PMCID: PMC12038549 DOI: 10.3748/wjg.v31.i15.103773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 02/23/2025] [Accepted: 04/07/2025] [Indexed: 04/18/2025] Open
Abstract
This article is based on a recent bibliometric analysis of research progress on liver aging. The liver is notable for its extraordinary ability to rejuvenate, thereby safeguarding and maintaining the organism's integrity. With advancing age, there is a noteworthy reduction in both the liver's size and blood circulation. Furthermore, the wide range of physiological alterations driven on by aging may foster the development of illnesses. Previous studies indicate that liver aging is linked to impaired lipid metabolism and abnormal gene expression associated with chronic inflammation. Factors such as mitochondrial dysfunction and telomere shortening accumulate, which may result in increased hepatic steatosis, which impacts liver regeneration, metabolism, and other functions. Knowing the structural and functional changes could help elderly adults delay liver aging. Increasing public awareness of anti-aging interventions is essential. Besides the use of dietary supplements, alterations in lifestyle, including changes in dietary habits and physical exercise routines, are the most efficacious means to decelerate the aging process of the liver. This article highlights recent advances in the mechanism research of liver aging and summarizes the promising intervention options to delay liver aging for preventing related diseases.
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Affiliation(s)
- Yu-Qin Yao
- College of Health Sciences, School of Life Sciences, Jiangsu Normal University, Xuzhou 221000, Jiangsu Province, China
| | - Qiong-Yue Cao
- College of Health Sciences, School of Life Sciences, Jiangsu Normal University, Xuzhou 221000, Jiangsu Province, China
| | - Zheng Li
- College of Health Sciences, School of Life Sciences, Jiangsu Normal University, Xuzhou 221000, Jiangsu Province, China
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Mi P, Cao X, Feng H, Wang H. Association of blood cadmium levels with epigenetic age acceleration in U.S. adults aged > 50 years. Front Public Health 2025; 13:1504830. [PMID: 40302773 PMCID: PMC12037496 DOI: 10.3389/fpubh.2025.1504830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 03/31/2025] [Indexed: 05/02/2025] Open
Abstract
Objectives DNA methylation (DNAm) is a sensitive biomarker of aging-related processes, and novel epigenetic-based "clocks" can estimate accelerated biological aging. Cadmium (Cd) can alter cellular processes that promote aging and disrupt global methylation patterns. However, few studies have investigated the association between blood Cd and accelerated aging. We aimed to investigate the association between blood Cd and four DNAm-based epigenetic age accelerations in individuals over 50 in the United States, using data from the National Health and Nutrition Examination Survey (NHANES). Methods DNAm-epigenetic biomarkers and blood Cd data from the NHANES database (1999-2002) were retrieved for this study. We evaluated four epigenetic ages: HorvathAge, HannumAge, PhenoAge, and GrimAge. Age acceleration was calculated by extracting the residuals from the regression of chronological age on each epigenetic age measure. We used weighted linear regression models and subgroup analyses to investigate the associations between blood Cd levels and these age accelerations, adjusting for potential confounding factors. Results Higher blood Cd levels (≥0.5 μg/dl) were significantly associated with increased age acceleration for PhenoAge (β = 1.37, P = 0.017) and GrimAge (β = 1.31, P = 0.003) in adjusted models. A significant association was also observed for HannumAge (β = 0.94, P = 0.016), although this association was not significant for continuous Cd levels (P = 0.111). No significant associations were found for HorvathAge. Subgroup analyses indicated consistent associations across demographic and lifestyle subgroups, with no significant interactions. Conclusions In this study, after adjusting for confounders, blood Cd levels were positively associated with PhenoAge acceleration and GrimAge acceleration in people over 50 in the United States. These results may be useful in proposing interventions in environmental exposures to slow the aging process and prevent age-related diseases.
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Affiliation(s)
- Panpan Mi
- Department of Orthopedic, Hebei PetroChina Central Hospital, Langfang, China
| | - Xu Cao
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, China
| | - Haixia Feng
- Department of Tuberculosis, Shandong Public Health Clinical Center, Jinan, Shandong, China
| | - Huijie Wang
- Department of Endoscopy, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang, China
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Rosic N. Unveiling the Anti-Aging Potential of Marine Natural Bioproducts. Mar Drugs 2025; 23:165. [PMID: 40278286 PMCID: PMC12028505 DOI: 10.3390/md23040165] [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: 02/12/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/26/2025] Open
Abstract
Aging is a natural process resulting in the progressive impairment of multiple functions in the human body, leading to a decline in cellular functionality and the development of aging-related diseases. External stress factors, such as ultraviolet (UV) radiation, pollution, and toxin exposure, increase oxidative stress, damage cellular repair mechanisms, and speed up aging processes. With the rise in the world's aging population, there are enlarged demands for the use of sustainable natural products in food, nutrient supplements and cosmetics that can slow down aging and prolong healthy life and longevity. Algae, including both macroalgae and microalgae, have been recognised as a source of valuable proteins, amino acids, fatty acids, vitamins, and minerals useful for human consumption and medical applications. With increasing demands for nutraceutical and pharmaceutical bioproducts from environmentally friendly resources, the biotechnological industry, over recent decades, has had to provide new, advanced solutions using modern high-throughput omics technologies. The application of proteomics in the area of discoveries of natural products with anti-aging properties has become more popular for wide industry applications. New proteomics profiling provides a better understanding of changes occurring in protein and peptide content, their structure, function and interactions, as well as the regulatory processes and molecular pathways. Mass spectrometry-based proteomics has been used for a wide range of applications including protein identification, characterisation, as well as quantification of proteins within the proteome and sub-proteome. The application of chemical proteomics facilitated the identification of natural products approach and included the synthesis of probes and target fishing, allowing the advanced identification of proteins of interest. This review focuses on marine macro- and microalgal anti-aging compounds and novel proteomics approaches, providing recent experimental evidence of their involvement in anti-aging processes that should facilitate their use in innovative approaches and sustainable biotechnological applications.
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Affiliation(s)
- Nedeljka Rosic
- Faculty of Health, Southern Cross University, Gold Coast, QLD 4225, Australia;
- Marine Ecology Research Centre, Southern Cross University, Lismore, NSW 2480, Australia
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Yue X, Liu H, Guo W, Gao Y, Shi S. Causal association between dietary factors and telomere length revealed by mendelian randomization. Sci Rep 2025; 15:11082. [PMID: 40169648 PMCID: PMC11961733 DOI: 10.1038/s41598-025-87693-2] [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: 07/05/2024] [Accepted: 01/21/2025] [Indexed: 04/03/2025] Open
Abstract
Observational studies have reported associations between dietary factors and telomere length. However, the inherent limitations of observational study designs render them susceptible to confounding and reverse causation biases. Therefore, this study aims to explore the association between dietary factors and telomere length using Mendelian Randomization (MR) to minimize the influence of confounding factors and reverse causality. The IEU Open GWAS project was the source of exposure and outcome datasets. The exposure datasets included 20 dietary factors. We conducted MR analyses to explore the relationship between dietary factors and telomere length. We used MRPRESSO and Radial-MR test to identify any level of multi-effect outliers. Heterogeneity and pleiotropic analysis were performed to ensure the accuracy of the results. The stability of the effect of significant results is assessed using multivariable Mendelian randomization (MVMR) and MR-lap. Two-sample MR analysis revealed a statistically significant association between dried fruit intake and telomere length (β = 0.223, 95% CI 0.091 to 0.356, PIVW=9.089 × 10^-4). After removing outliers and reanalyzing the data, the association remained significant (β = 0.163, 95% CI: 0.163 0.090 to 0.235, PIVW-FE=7.323 × 10^-5), with no significant pleiotropy detected in sensitivity analyses. Following adjustment for confounders, the MVMR results and MR-lap results continued to support a causal relationship between dried fruit intake and telomere length. Other dietary factors' effects on telomere length still need further confirmation. Our findings suggest a potential causal relationship between dried fruit intake and longer telomere length. This finding highlights potential dietary strategies for exploring the beneficial effects of dried fruit intake on preventing diseases and extending lifespan.
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Affiliation(s)
- Xinghai Yue
- Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Hongfei Liu
- Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Wenzhao Guo
- Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Yuhang Gao
- Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Shaoshun Shi
- Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
- Department of Intensive care unit, the Second Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
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Vazquez-Moreno M, Perales-Herrera A, Ramírez-Silva I, Martínez-Gómez LE, García-Cerón A, Paredes-Barrientos JC, Hernández-Mendoza H, Martinez-Garza S, Murillo-Ortiz B, Cruz M. Dietary Zinc Intake and the Association of Insulin Level and HOMA-IR with Telomere Shortening in Mexican Children. Biol Trace Elem Res 2025; 203:2114-2121. [PMID: 39110381 DOI: 10.1007/s12011-024-04329-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 07/25/2024] [Indexed: 03/20/2025]
Abstract
PURPOSE The relationship between dietary zinc (Zn) intake, metabolic diseases, and telomere length has been little explored in the children population. This observational cross-sectional study assesses the association between obesity (OB), cardiometabolic traits, telomere length, and dietary Zn intake in children with normal weight (NW) and OB from Mexico City. METHODS Anthropometric data, blood pressure, biochemical measurements, the homeostatic model assessment of insulin resistance (HOMA-IR) and leucocyte telomere length (determined by quantitative-PCR) were analyzed in 171 children with NW and 172 with OB. Furthermore, dietary Zn intake was evaluated in 117 children NW and 120 with OB. RESULTS Telomere shortening was associated with fasting plasma insulin (FPI) and HOMA-IR in NW (beta coefficient [β]FPI = -0.022 ± 0.008, p = 0.009; βHOMA-IR = -0.096 ± 0.040, p = 0.020) and OB (βFPI = -0.007 ± 0.002, p = 0.003; βHOMA-IR = -0.034 ± 0.012, p = 0.005) children. Dietary Zn intake resulted negatively associated with FPI (β = -2.418 ± 0.764, p = 0.002) and HOMA-IR (β = -0.399 ± 0.014, p = 0.009) in children with OB. Then, in children with OB, the association between FPI, HOMA-IR, and telomere shortening was evaluated separately in groups of low, medium, and high dietary Zn intake (according to tertiles). The association between FPI, HOMA-IR, and telomere shortening was not significant in the high Zn intake group (PFPI = 0.633; PHOMA-IR = 0.567). CONCLUSION Our results suggest that a high Zn intake may ameliorate the telomere shortening related to high FPI and HOMA-IR.
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Affiliation(s)
- Miguel Vazquez-Moreno
- Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Delegación Cuauhtémoc, C.P. 06720, Ciudad de Mexico, México
| | - Araceli Perales-Herrera
- Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Delegación Cuauhtémoc, C.P. 06720, Ciudad de Mexico, México
- Programa de Licenciatura en Nutrición, Universidad del Centro de México, S.L.P, CP, 78250, San Luis, México
| | - Ivonne Ramírez-Silva
- Centro de Investigación en Nutrición y Salud, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico, Av. Universidad 655, Col. Santa María Ahuacatitlán, Cerrada Los Pinos y Caminera, C.P. 62100, Cuernavaca, Morelos, Mexico
| | - Laura E Martínez-Gómez
- Laboratorio de Gerociencias. Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Secretaría de Salud, Mexico City, Mexico
| | - Angélica García-Cerón
- Unidad de Medicina Familiar No. 23, Instituto Mexicano del Seguro Social, Ciudad de Mexico, México
| | | | - Héctor Hernández-Mendoza
- Instituto de Investigación de Zonas Desérticas, Universidad Autónoma de San Luis Potosí, S.L.P, Altair 200, CP, 78377, San Luis, México
- Universidad del Centro de México, Capitán Caldera 75, CP, 78250, San Luis, S.L.P, México
| | - Sandra Martinez-Garza
- Instituto Mexicano del Seguro Social, Unidad de Investigación en Epidemiología Clínica- Unidad Médica de Alta Especialidad No. 1 Bajío- OOAD Guanajuato, León- Guanajuato, México
| | - Blanca Murillo-Ortiz
- Instituto Mexicano del Seguro Social, Unidad de Investigación en Epidemiología Clínica- Unidad Médica de Alta Especialidad No. 1 Bajío- OOAD Guanajuato, León- Guanajuato, México.
| | - Miguel Cruz
- Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Delegación Cuauhtémoc, C.P. 06720, Ciudad de Mexico, México.
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11
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Kureel SK, Maroto R, Davis K, Sheetz M. Cellular mechanical memory: a potential tool for mesenchymal stem cell-based therapy. Stem Cell Res Ther 2025; 16:159. [PMID: 40165288 PMCID: PMC11960036 DOI: 10.1186/s13287-025-04249-x] [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: 08/21/2024] [Accepted: 02/20/2025] [Indexed: 04/02/2025] Open
Abstract
Recent studies have shown that mechanical properties such as extracellular matrix stiffness, fluid flow, weight loading, compression, and stretching can affect cellular functions. Some examples of cell responses to mechanical properties could be the migration of cancer cells from rigid to soft surfaces or the differentiation of fibroblasts into myofibroblasts. Cellular responses to mechanical changes can modify the insertion of proteins in the extracellular matrix (ECM), causing an increase in tissue stiffness with functional consequences. In general, mechanical and physical factors can affect any kind of cell phenotype in culture conditions and in vivo tissues. Cells sense mechanical stimuli by applying force and restructuring their shape and functions in response to the resistance of the stimuli. Furthermore, mechanical triggers can develop a "memory" for altering cellular plasticity and adaptation. This phenomenon is called cellular mechanical memory (CMM), a singular feature of mesenchymal stem cells (MSCs). Controlled targeting of CMM may resolve the scarcity of viable cells needed for cell based therapy (CBT) and implement studies concerning cancer research, fibrosis, and senescence. This review focusses on cells from the mesodermal lineage, such as MSCs, fibroblasts and chondrocytes, and the role of CMM as a potential target for CBT.
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Affiliation(s)
- Sanjay Kumar Kureel
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
| | - Rosario Maroto
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Kristen Davis
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA
| | - Michael Sheetz
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA
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12
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Liu Z, Sun C, Zhang Z, Jiang Y, Zhao C. Telomeres in skin aging. Biogerontology 2025; 26:83. [PMID: 40159528 DOI: 10.1007/s10522-025-10228-9] [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: 02/06/2025] [Accepted: 03/20/2025] [Indexed: 04/02/2025]
Abstract
Skin aging is influenced by both intrinsic and extrinsic factors. The gradual manifestation of changes in telomere length and telomerase activity, as crucial indicators of aging, elucidates the underlying mechanism of skin aging. This review aims to comprehensively analyze the association between telomeres and aging, along with their impact on skin biological function. Firstly, we summarize the structure and function of telomeres and their role in cell division. Subsequently, we discuss the mechanisms through which telomere regulation contributes to aging processes while analyzing its involvement in skin aging by elaborating on biological markers. Furthermore, this paper presents a summary of recent research progress that reveals the correlation between telomere length and skin aging as well as model building methods; it also proposes telomere length as a potential indicator for predicting skin aging. Finally, anti-aging strategies based on telomere protection are discussed including drug therapy and lifestyle adjustments. This paper provides a systematic overview of the role played by telomeres in the field of skin aging for the first time, offering new perspectives and ideas for future prevention and treatment.
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Affiliation(s)
- Zibin Liu
- Beijing Qingyan Boshi Health Management Co., Ltd, No. 36, Chuangyuan Road, Chaoyang District, Beijing, China
| | - Chang Sun
- Beijing Qingyan Boshi Health Management Co., Ltd, No. 36, Chuangyuan Road, Chaoyang District, Beijing, China
| | - Zhaofeng Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, China
- Peking University Medical-Qingyan Boshi Joint Laboratory for Skin Nutrition and Anti-Aging, School of Public Health, Peking University, Beijing, China
| | - Yanfei Jiang
- Beijing Qingyan Boshi Health Management Co., Ltd, No. 36, Chuangyuan Road, Chaoyang District, Beijing, China.
| | - Chunyue Zhao
- Beijing Qingyan Boshi Health Management Co., Ltd, No. 36, Chuangyuan Road, Chaoyang District, Beijing, China.
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13
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Luo Q, Liu L. Adipose-derived stem cells regulate mitochondrial dynamics to alleviate the aging of HFF-1 cells. In Vitro Cell Dev Biol Anim 2025; 61:357-367. [PMID: 39871034 DOI: 10.1007/s11626-025-01017-2] [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: 07/15/2024] [Accepted: 01/04/2025] [Indexed: 01/29/2025]
Abstract
The objective of this study is to explore how adipose-derived stem cells (ASCs) regulate mitochondrial structure and function and the impact of this regulation on slowing cellular senescence. HFF-1 cells were induced by H2O2 to establish a cellular senescence model, and ASCs or Mdivi-1 (mitochondrial fission inhibitor) was added. MTT examined the cell proliferation; flow cytometry detected mitochondrial membrane potential as well as apoptosis and cell cycle; kit measured ATP production; ELISA analyzed the levels of interleukin-6 (IL-6), interleukin 1 beta (IL-1β), tumor necrosis factor alpha-like (TNF-α), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD); Western blotting and qRT-PCR detected the expression of protein and mRNA levels; and β-galactosidase staining observed the degree of cellular senescence. Compared to normal HFF-1 cells, senescent HFF-1 cells exhibited weaker proliferative capacity, marked apoptosis, and G0-G1 cell cycle arrest. These cells also showed lower mitochondrial membrane potential and ATP production, higher expression of inflammatory factors, oxidative damage, and increased levels of senescence. Treatment with Mdivi-1 or ASCs enhanced HFF-1 cell proliferation, reduced apoptosis and cell cycle arrest, increased mitochondrial membrane potential and ATP production, decreased the expression of inflammatory factors, and mitigated oxidative stress, thereby reducing the degree of cellular senescence. Concurrent intervention with Mdivi-1 and ASCs further diminishes the impacts of cellular senescence. In conclusion, ASCs regulate mitochondrial dynamics (promoting mitochondrial fusion and inhibiting mitochondrial fission), enhance ATP production, and upregulate mitochondrial membrane potential, thereby alleviating cell cycle arrest, apoptosis, inflammatory responses, and oxidative stress induced by senescence in HFF-1 cells.
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Affiliation(s)
- Qi Luo
- Department of Plastic Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, China
| | - Ling Liu
- Department of Outpatient Service, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, Hunan, China.
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14
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Xu G, Liu Z, Hou P. Causality of Childhood and Adult Body Mass Index on Sick Sinus Syndrome: A Mendelian Randomization Study. Cureus 2025; 17:e80913. [PMID: 40125526 PMCID: PMC11929112 DOI: 10.7759/cureus.80913] [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] [Accepted: 03/19/2025] [Indexed: 03/25/2025] Open
Abstract
Background The relationship between body mass index (BMI) and the risk of sick sinus syndrome (SSS) remains unclear. Clarifying the impact of BMI on SSS at different life stages is essential for advancing precision medicine and implementing effective prevention strategies to reduce the burden of SSS. Methods The causalities of childhood and adult BMI with SSS were investigated by univariate and multivariate Mendelian randomization. Reverse causalities were also explored to improve the accuracy of causality findings. Different sources of exposure data were used for replication analysis, and the effects of sample overlap were investigated using MRlap. The stability of the results was further enhanced through meta-analysis. Results There was a positive correlation of adult BMI with the risk of SSS in both the FinnGen (odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.01-1.35, P = 0.031) and Integrative Epidemiology Unit (IEU) open genome-wide association study (GWAS) project (OR = 1.18, 95% CI 1.04-1.34, P = 0.009) databases. The causality remained valid after the correction of telomere length. There was no causality detected between childhood BMI and SSS, as determined by independent studies of the Early Growth Genetics (EGG) 2020 (OR = 1.06, 95% CI 0.89-1.27, P = 0.513) and EGG2015 (OR = 1.02, 95% CI 0.97-1.09, P = 0.423). Meta-analysis results further confirmed the reliability of the causal inference. Conclusions The findings indicate that elevated BMI in adults, particularly among middle-aged and elderly populations, increases the risk of developing SSS. In contrast, no causal relationship was observed between childhood BMI and SSS, suggesting that the influence of BMI on SSS susceptibility may predominantly emerge during later life stages. These results highlight the need for targeted public health interventions to address adult obesity as a modifiable risk factor for SSS.
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Affiliation(s)
- Guanzhen Xu
- Graduate School, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, CHN
| | - Zhuang Liu
- Cardiology Department, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, CHN
| | - Ping Hou
- Graduate School, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, CHN
- Cardiology Department, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, CHN
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15
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Maria MKM, Abdel Moniem EM, Hanafy AK, Farag DBE, Radwan IA, Abbass MMS, El Moshy S, Rady D, Dörfer CE, Fawzy El-Sayed KM. Age-Related Oral and Para-Oral Tissue Disorders: The Evolving Therapeutic and Diagnostic Potential of Exosomes. Dent J (Basel) 2025; 13:106. [PMID: 40136734 PMCID: PMC11941486 DOI: 10.3390/dj13030106] [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: 01/02/2025] [Revised: 02/14/2025] [Accepted: 02/24/2025] [Indexed: 03/27/2025] Open
Abstract
This review highlights the key molecular and cellular mechanisms contributing to aging, such as DNA damage, mitochondrial dysfunction, telomere shortening, protein dysfunction, and defective autophagy. These biological mechanisms are involved in various oral health conditions prevalent in the elderly, including periodontal disease, oral cancer, xerostomia, dental caries, and temporomandibular joint disorders. Exosomes generated by mesenchymal stem cells possess substantial therapeutic potential. These exosomes are nanosized extracellular vesicles derived from cells and are involved in essential intercellular communication and tissue homeostasis. The exosome-based therapies proved superior to traditional cell-based approaches, due to lower immunogenicity, ease of storage, and avoidance of complications associated with cell transplantation. Furthermore, the diagnostic potential of exosomes as non-invasive biomarkers for aging processes and age-related oral diseases offers insights into disease diagnosis, staging, and monitoring. Among the challenges and future perspectives of translating exosome research from preclinical studies to clinical applications is the need for standardized procedures to fully harness the therapeutic and diagnostic capabilities of exosomes.
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Affiliation(s)
- Mohamed Khaled Mohamed Maria
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
| | | | - Ahmed Khaled Hanafy
- Oral Biology Department, Faculty of Dentistry, Egyptian Russian University, Badr City 11829, Egypt;
| | - Dina B. E. Farag
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
| | - Israa Ahmed Radwan
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Marwa M. S. Abbass
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Sara El Moshy
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Dina Rady
- Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt; (M.K.M.M.); (D.B.E.F.); (I.A.R.); (M.M.S.A.); (S.E.M.); (D.R.)
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
| | - Christof E. Dörfer
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, 24118 Kiel, Germany;
| | - Karim M. Fawzy El-Sayed
- Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo 12588, Egypt
- Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian Albrechts University, 24118 Kiel, Germany;
- Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University, Cairo 12613, Egypt
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16
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Lee K, Kim M. Evolutionary Insights into Irisin/FNDC5: Roles in Aging and Disease from Drosophila to Mammals. Biomolecules 2025; 15:261. [PMID: 40001564 PMCID: PMC11853655 DOI: 10.3390/biom15020261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 02/03/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
The Irisin/FNDC5 protein family has emerged as a pivotal link between exercise and the prevention of age-associated diseases. Irisin is highly expressed during exercise from skeletal and cardiac muscle cells, playing a critical role in mediating systemic health benefits through its actions on various tissues. However, Irisin levels decline with age, correlating with a heightened incidence of diseases such as muscle weakness, cardiovascular disorders, and neurodegeneration. Notably, the administration of Irisin has shown significant potential in both preventing and treating these conditions. Recently, an Irisin/FNDC5 homolog was identified in an invertebrate Drosophila model, providing valuable insights into its conserved role in exercise physiology. Importantly, Irisin/FNDC5 has been demonstrated to regulate autophagy-a process essential for clearing excessive nutrients, toxic aggregates, and dysfunctional organelles-in both flies and mammals. Dysregulated autophagy is often implicated in age-related diseases, highlighting its relevance to Irisin/FNDC5's functions. These findings deepen our understanding of Irisin/FNDC5's roles and its potential as a therapeutic target for mitigating aging-related health decline. Further studies are needed to elucidate the precise mechanisms by which Irisin regulates autophagy and its broader impact on physiological aging and related diseases.
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Affiliation(s)
| | - Myungjin Kim
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA;
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17
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Costa CM, Pedrosa SS, Kirkland JL, Reis F, Madureira AR. The senotherapeutic potential of phytochemicals for age-related intestinal disease. Ageing Res Rev 2025; 104:102619. [PMID: 39638096 DOI: 10.1016/j.arr.2024.102619] [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: 09/17/2024] [Revised: 11/18/2024] [Accepted: 12/02/2024] [Indexed: 12/07/2024]
Abstract
During the last few decades, life expectancy has increased worldwide along with the prevalence of several age-related diseases. Among aging pathways, cellular senescence and chronic inflammation (or "inflammaging") appear to be connected to gut homeostasis and dysbiosis of the microbiome. Cellular senescence is a state of essentially irreversible cell cycle arrest that occurs in response to stress. Although senescent cells (SC) remain metabolically active, they do not proliferate and can secrete inflammatory and other factors comprising the senescence-associated secretory phenotype (SASP). Accumulation of SCs has been linked to onset of several age-related diseases, in the brain, bones, the gastrointestinal tract, and other organs and tissues. The gut microbiome undergoes substantial changes with aging and is tightly interconnected with either successful (healthy) aging or disease. Senotherapeutic drugs are compounds that can clear senescent cells or modulate the release of SASP factors and hence attenuate the impact of the senescence-associated pro-inflammatory state. Phytochemicals, phenolic compounds and terpenes, which have antioxidant and anti-inflammatory activities, could also be senotherapeutic given their ability to act upon senescence-linked cellular pathways. The aim of this review is to dissect links among the gut microbiome, cellular senescence, inflammaging, and disease, as well as to explore phytochemicals as potential senotherapeutics, focusing on their interactions with gut microbiota. Coordinated targeting of these inter-related processes might unveil new strategies for promoting healthy aging.
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Affiliation(s)
- Célia Maria Costa
- Universidade Católica Portuguesa, CBQF-Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, Porto 4169-005, Portugal.
| | - Sílvia Santos Pedrosa
- Biorbis, Unipessoal LDA, Edifício de Biotecnologia da Universidade Católica Portuguesa, Rua Diogo Botelho 1327, Porto 4169-005, Portugal.
| | - James L Kirkland
- Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
| | - Flávio Reis
- Institute of Pharmacology and Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra 3004-504, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3000-548, Portugal; Clinical Academic Center of Coimbra, Coimbra 3004-531, Portugal.
| | - Ana Raquel Madureira
- Universidade Católica Portuguesa, CBQF-Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, Porto 4169-005, Portugal.
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18
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Fountoulakis N, Miyamoto Y, Pavkov ME, Karalliedde J, Maltese G. Pathophysiology of vascular ageing and the effect of novel cardio-renal protective medications in preventing progression of chronic kidney disease in people living with diabetes. Diabet Med 2025; 42:e15464. [PMID: 39497615 PMCID: PMC11733662 DOI: 10.1111/dme.15464] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 10/15/2024] [Accepted: 10/16/2024] [Indexed: 01/16/2025]
Abstract
AIM Among people with diabetes those with chronic kidney disease (CKD) have a reduced life expectancy with increased risk of cardiovascular disease (CVD) a major contributor to morbidity and mortality. CKD related to diabetes is growing worldwide and is one of the leading causes of kidney failure globally. Diabetes is associated with accelerated vascular ageing and the related mechanisms and mediators that drive the progression of CKD and CVD disease in people with diabetes may help provide insights into the pathophysiology of cardio-renal complications and guide treatment interventions in people with diabetes. METHODS We conducted a narrative review of the literature using PubMed for English language articles that contained keywords that related to diabetes, chronic or diabetic kidney disease, ageing, cellular senescence, arterial stiffness, Klotho and sirtuins, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, renin angiotensin aldosterone system (RAAS) and glucagon-like peptide-1 (GLP-1) receptor agonists. RESULTS Progressive kidney disease in diabetes is associated with accelerated ageing driven in part by multiple processes such as cellular senescence, inflammation, oxidative stress and circulating uremic toxins. This accelerated ageing phenotype contributes to increased arterial stiffness, endothelial dysfunction, cognitive decline and muscle wasting, thereby elevating morbidity and mortality in individuals with diabetes and CKD. Deficiency of the kidney-derived anti-ageing hormone Klotho and reduced sirtuin levels play pivotal roles in these ageing pathways. Dietary, lifestyle and pharmacological interventions targeting vascular ageing may help reduce the progression of CKD and associated CVD in people with diabetes. The current standard of care and pillars of treatment for kidney disease such as RAAS inhibitors, SGLT-2 inhibitors and GLP-1 receptor agonists all influence pathways involved in vascular ageing. CONCLUSIONS A multifactorial intervention to prevent the development of CKD by targeting traditional risk factors as well as treatment with novel agents with cardio-renal beneficial effects can prevent accelerated ageing and extend lifespan in people with diabetes.
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Affiliation(s)
- Nikolaos Fountoulakis
- School of Cardiovascular, Metabolic Medicine and SciencesKing's College LondonLondonUK
| | | | - Meda E. Pavkov
- Centers for Disease Control and PreventionAtlantaGeorgiaUSA
| | - Janaka Karalliedde
- School of Cardiovascular, Metabolic Medicine and SciencesKing's College LondonLondonUK
| | - Giuseppe Maltese
- School of Cardiovascular, Metabolic Medicine and SciencesKing's College LondonLondonUK
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19
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Pandey KB. From bench to bedside: translational insights into aging research. FRONTIERS IN AGING 2025; 6:1492099. [PMID: 39926027 PMCID: PMC11802818 DOI: 10.3389/fragi.2025.1492099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 01/09/2025] [Indexed: 02/11/2025]
Abstract
Aging research has rapidly advanced from fundamental discoveries at the molecular and cellular levels to promising clinical applications. This review discusses the critical translational insights that bridge the gap between bench research and bedside applications, highlighting key discoveries in the mechanisms of aging, biomarkers, and therapeutic interventions. It underscores the importance of interdisciplinary approaches and collaboration among scientists, clinicians, and policymakers to address the complexities of aging and improve health span.
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Affiliation(s)
- Kanti Bhooshan Pandey
- CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, India
- Faculty of Biological Sciences, Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, India
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20
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Sánchez-Badajos S, Ortega-Vázquez A, López-López M, Monroy-Jaramillo N. Valproic Acid and Lamotrigine Differentially Modulate the Telomere Length in Epilepsy Patients. J Clin Med 2025; 14:255. [PMID: 39797337 PMCID: PMC11720991 DOI: 10.3390/jcm14010255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 12/30/2024] [Accepted: 01/02/2025] [Indexed: 01/13/2025] Open
Abstract
Background/Objectives: Antiseizure drugs (ASDs) are the primary therapy for epilepsy, and the choice varies according to seizure type. Epilepsy patients experience chronic mitochondrial oxidative stress and increased levels of pro-inflammatory mediators, recognizable hallmarks of biological aging; however, few studies have explored aging markers in epilepsy. Herein, we addressed for the first time the impact of ASDs on molecular aging by measuring the telomere length (TL) and mtDNA copy number (mtDNA-CN). Methods: We used real-time quantitative PCR (QPCR) in epilepsy patients compared to matched healthy controls (CTs) and assessed the association with plasma levels of ASDs and other clinical variables. The sample comprised 64 epilepsy patients and 64 CTs. Patients were grouped based on monotherapy with lamotrigine (LTG) or valproic acid (VPA), and those treated with a combination therapy (LTG + VPA). Multivariable logistic regression was applied to analyze the obtained data. Results: mtDNA-CN was similar between patients and controls, and none of the comparisons were significant for this marker. TL was shorter in not seizure-free patients than in CTs (1.50 ± 0.35 vs. 1.68 ± 0.34; p < 0.05), regardless of the ASD therapy. These patients exhibited the highest proportion of adverse drug reactions. TL was longer in patients on VPA monotherapy, followed by patients on LTG monotherapy and patients on an LTG + VPA combined scheme (1.77 ± 0.24; 1.50 ± 0.32; 1.36 ± 0.37, respectively; p < 0.05), suggesting that ASD treatment differentially modulates TL. Conclusions: Our findings suggest that clinicians could consider TL measurements to decide the best ASD treatment option (VPA and/or LTG) to help predict ASD responses in epilepsy patients.
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Affiliation(s)
- Salvador Sánchez-Badajos
- Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Mexico City 04960, Mexico;
| | - Alberto Ortega-Vázquez
- Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Unidad Xochimilco, Mexico City 04960, Mexico; (A.O.-V.); (M.L.-L.)
| | - Marisol López-López
- Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Unidad Xochimilco, Mexico City 04960, Mexico; (A.O.-V.); (M.L.-L.)
| | - Nancy Monroy-Jaramillo
- Departamento de Genética, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez (INNNMVS), Mexico City 14269, Mexico
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21
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Dansereau SJ, Cui H, Dartawan RP, Sheng J. The Plethora of RNA-Protein Interactions Model a Basis for RNA Therapies. Genes (Basel) 2025; 16:48. [PMID: 39858595 PMCID: PMC11765398 DOI: 10.3390/genes16010048] [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: 11/30/2024] [Revised: 12/25/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025] Open
Abstract
The notion of RNA-based therapeutics has gained wide attractions in both academic and commercial institutions. RNA is a polymer of nucleic acids that has been proven to be impressively versatile, dating to its hypothesized RNA World origins, evidenced by its enzymatic roles in facilitating DNA replication, mRNA decay, and protein synthesis. This is underscored through the activities of riboswitches, spliceosomes, ribosomes, and telomerases. Given its broad range of interactions within the cell, RNA can be targeted by a therapeutic or modified as a pharmacologic scaffold for diseases such as nucleotide repeat disorders, infectious diseases, and cancer. RNA therapeutic techniques that have been researched include, but are not limited to, CRISPR/Cas gene editing, anti-sense oligonucleotides (ASOs), siRNA, small molecule treatments, and RNA aptamers. The knowledge gleaned from studying RNA-centric mechanisms will inevitably improve the design of RNA-based therapeutics. Building on this understanding, we explore the physiological diversity of RNA functions, examine specific dysfunctions, such as splicing errors and viral interactions, and discuss their therapeutic implications.
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Affiliation(s)
| | | | | | - Jia Sheng
- Department of Chemistry, The RNA Institute, University at Albany, SUNY, 1400 Washington Ave Extension, Albany, NY 12222, USA; (S.J.D.); (H.C.)
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22
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Kobayashi H, Imanaka S. Exploring potential pathways from oxidative stress to ovarian aging. J Obstet Gynaecol Res 2025; 51:e16166. [PMID: 39572911 DOI: 10.1111/jog.16166] [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: 09/19/2024] [Accepted: 11/12/2024] [Indexed: 12/13/2024]
Abstract
AIM In developed nations, women have increasingly deferred childbearing, leading to a rise in demand for infertility treatments and the widespread use of assisted reproductive technologies. However, despite advancements in in vitro fertilization (IVF), live birth rates among women over 40 remain suboptimal. Mitochondrial dysfunction is widely recognized as a key factor in the processes driving the age-related deterioration in both the quantity and quality of oocytes. We aim to summarize current insights into ovarian aging, with a particular focus on pathways that impair mitochondrial function, and explore directions for future research. METHODS Electronic databases were searched for articles published up to June 30, 2024. RESULTS Ongoing ovulation, luteolysis, and menstruation trigger exogenous reactive oxygen species (ROS)-mediated oxidative stress that damages mitochondrial DNA. This, in turn, reduces nuclear gene expression, compromises mitochondrial oxidative phosphorylation, and diminishes adenosine 5' triphosphate production. Persistent endogenous ROS further exacerbate mitochondrial DNA damage and aneuploidy, ultimately causing irreversible chromosomal abnormalities, leading to oocyte aging. CONCLUSIONS We have delineated the pathway from oxidative stress to ovarian aging. Early detection and management of ovarian aging present challenges and opportunities to enhance IVF treatment strategies.
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Affiliation(s)
- Hiroshi Kobayashi
- Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, Kashihara, Japan
- Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Japan
| | - Shogo Imanaka
- Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, Kashihara, Japan
- Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Japan
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23
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Hejazian SM, Hejazian SS, Mostafavi SM, Hosseiniyan SM, Montazersaheb S, Ardalan M, Zununi Vahed S, Barzegari A. Targeting cellular senescence in kidney diseases and aging: A focus on mesenchymal stem cells and their paracrine factors. Cell Commun Signal 2024; 22:609. [PMID: 39696575 DOI: 10.1186/s12964-024-01968-1] [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: 09/15/2024] [Accepted: 11/28/2024] [Indexed: 12/20/2024] Open
Abstract
Cellular senescence is a phenomenon distinguished by the halting of cellular division, typically triggered by DNA injury or numerous stress-inducing factors. Cellular senescence is implicated in various pathological and physiological processes and is a hallmark of aging. The presence of accumulated senescent cells, whether transiently (acute senescence) or persistently (chronic senescence) plays a dual role in various conditions such as natural kidney aging and different kidney disorders. Elevations in senescent cells and senescence-associated secretory phenotype (SASP) levels correlate with decreased kidney function, kidney ailments, and age-related conditions. Strategies involving senotherapeutic agents like senolytics, senomorphics, and senoinflammation have been devised to specifically target senescent cells. Mesenchymal stem cells (MSCs) and their secreted factors may also offer alternative approaches for anti-senescence interventions. The MSC-derived secretome compromises significant therapeutic benefits in kidney diseases by facilitating tissue repair via anti-inflammatory, anti-fibrosis, anti-apoptotic, and pro-angiogenesis effects, thereby improving kidney function and mitigating disease progression. Moreover, by promoting the clearance of senescent cells or modulating their secretory profiles, MSCs could potentially reverse some age-related declines in kidney function.This review article intends to shed light on the present discoveries concerning the role of cellular senescence in kidney aging and diseases. Furthermore, it outlines the role of senotherapeutics utilized to alleviate kidney damage and aging. It also highlights the possible impact of MSCs secretome on mitigating kidney injury and prolonging lifespan across various models of kidney diseases as a novel senotherapy.
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Affiliation(s)
| | - Seyyed Sina Hejazian
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyyedeh Mina Mostafavi
- Ayatollah Taleghani Hospital, Research Development Unit, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Soheila Montazersaheb
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | | | - Abolfazl Barzegari
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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24
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Borrego-Ruiz A, Borrego JJ. Epigenetic Mechanisms in Aging: Extrinsic Factors and Gut Microbiome. Genes (Basel) 2024; 15:1599. [PMID: 39766866 PMCID: PMC11675900 DOI: 10.3390/genes15121599] [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: 11/23/2024] [Revised: 12/03/2024] [Accepted: 12/06/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND/OBJECTIVES Aging is a natural physiological process involving biological and genetic pathways. Growing evidence suggests that alterations in the epigenome during aging result in transcriptional changes, which play a significant role in the onset of age-related diseases, including cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. For this reason, the epigenetic alterations in aging and age-related diseases have been reviewed, and the major extrinsic factors influencing these epigenetic alterations have been identified. In addition, the role of the gut microbiome and its metabolites as epigenetic modifiers has been addressed. RESULTS Long-term exposure to extrinsic factors such as air pollution, diet, drug use, environmental chemicals, microbial infections, physical activity, radiation, and stress provoke epigenetic changes in the host through several endocrine and immune pathways, potentially accelerating the aging process. Diverse studies have reported that the gut microbiome plays a critical role in regulating brain cell functions through DNA methylation and histone modifications. The interaction between genes and the gut microbiome serves as a source of adaptive variation, contributing to phenotypic plasticity. However, the molecular mechanisms and signaling pathways driving this process are still not fully understood. CONCLUSIONS Extrinsic factors are potential inducers of epigenetic alterations, which may have important implications for longevity. The gut microbiome serves as an epigenetic effector influencing host gene expression through histone and DNA modifications, while bidirectional interactions with the host and the underexplored roles of microbial metabolites and non-bacterial microorganisms such as fungi and viruses highlight the need for further research.
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Affiliation(s)
- Alejandro Borrego-Ruiz
- Departamento de Psicología Social y de las Organizaciones, Universidad Nacional de Educación a Distancia (UNED), 28040 Madrid, Spain;
| | - Juan J. Borrego
- Departamento de Microbiología, Universidad de Málaga, 29071 Málaga, Spain
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25
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Bem MMS, Paraizo-Horvath CMS, Freitas PS, Brito TRP. Is it possible that menopause is associated with telomere length? Findings of an integrative review. Climacteric 2024; 27:521-525. [PMID: 39023108 DOI: 10.1080/13697137.2024.2376193] [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: 06/27/2023] [Revised: 06/11/2024] [Accepted: 06/30/2024] [Indexed: 07/20/2024]
Abstract
OBJECTIVE Knowing the important repercussions of menopause for women's health and that female longevity can be better understood through studies based on aging biomarkers, studies on the relationship between menopause and telomere shortening may help to better understand this stage of life. This study aimed to analyze what research has been produced regarding the relationship between menopause and telomere length. METHODS This integrative literature review included searches in PubMed, CINAHL, LILACS, Web of Science and Scopus databases. Four studies were selected for the final sample. RESULTS The findings of these studies indicate that older age for menopause and longer reproductive life (difference between age at menopause and menarche) are associated with longer telomeres, that is, with longevity. CONCLUSION The relationship between menopause and telomere length is uncertain. The small number of studies included in this review, and the fact that the results indicate that the relationship between menopause and telomere length may be dependent on the stage of the menopause and race/ethnicity, suggest that additional research focusing on these variables should be carried out.
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Affiliation(s)
- M M S Bem
- Nursing School, Federal University of Alfenas, Alfenas, Brazil
| | | | - P S Freitas
- Nursing School, Federal University of Alfenas, Alfenas, Brazil
| | - T R P Brito
- Faculty of Nutrition, Federal University of Alfenas, Alfenas, Brazil
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26
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Li C, Zhang Y, Zhang K, Fu H, Lin L, Cai G, Zhang X, Yang X, Zhang Z, Yang Z, Zhang B. Association Between Ultra-Processed Food Consumption and Leucocyte Telomere Length: A cross-sectional study of UK Biobank. J Nutr 2024; 154:3060-3069. [PMID: 38735573 DOI: 10.1016/j.tjnut.2024.05.001] [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: 01/18/2024] [Revised: 04/23/2024] [Accepted: 05/01/2024] [Indexed: 05/14/2024] Open
Abstract
OBJECTIVE This study aimed to investigate the association between consumption of ultra-processed foods (UPFs) and leucocyte telomere length (LTL). METHODS This cross-sectional study utilized data from the UK Biobank, including a total of 64,690 participants. LTL was measured using Q-PCR with natural logarithmic conversion and Z-score normalization. Dietary data were collected through a 24-hour recall questionnaire from 2009 to 2010. UPFs were identified using the Nova food classification and analyzed as either a continuous or categorical variable respectively. Multiple linear regression models were employed to analyze the association between UPF consumption and LTL. RESULTS The included participants had an average age of 56.26 years, of whom 55.2% were female. After adjusting for sociodemographic, lifestyle-related and anthropometric variables, LTL exhibited a decrease of 0.005 (95% CI: -0.007, -0.002) with one UPF serving/day increase. Compared to participants consuming ≤ 3.5 servings/day, those consuming 3.5 to < 6, 6 to ≤ 8 and > 8 servings/day showed a shortening of LTL by 0.025 (95% CI: -0.047, -0.004), 0.034 (95% CI: -0.055, -0.012) and 0.038 (95% CI: -0.062, -0.015), respectively (P for trend = 0.001). Subgroup analyses by UPF subclasses revealed that consumption of ready-to-eat/heated food (β = -0.008, 95% CI: -0.014, -0.002), beans and potatoes (β = -0.024, 95% CI: -0.039, -0.009), animal-based products (β = -0.011, 95% CI: -0.019, -0.004), artificial sugar (β = -0.014, 95% CI: -0.025, -0.004), and beverages (β = -0.005, 95% CI: -0.009, -0.001) showed negative associations with LTL. Conversely, breakfast cereals (β = 0.020, 95% CI: 0.004, 0.036) and vegetarian alternatives (β = 0.057, 95% CI: 0.027, 0.086) showed positive correlations with LTL. CONCLUSIONS Our study found that a higher consumption of total UPFs was associated with a shorter LTL. However, some subclass UPFs may be associated with longer LTL, depending on their nutritional composition.
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Affiliation(s)
- Chunhao Li
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Yuchun Zhang
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Ke Zhang
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Hongna Fu
- Division of Emergency Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; NHC Key Laboratory on Assisted Circulation, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China
| | - Luyang Lin
- Division of Emergency Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; NHC Key Laboratory on Assisted Circulation, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China
| | - Guoyi Cai
- Division of Emergency Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; NHC Key Laboratory on Assisted Circulation, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China
| | - Xiaojun Zhang
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Xingfen Yang
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Zheqing Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Zhen Yang
- Division of Emergency Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China; NHC Key Laboratory on Assisted Circulation, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
| | - Bo Zhang
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, China.
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27
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Borrego-Ruiz A, Borrego JJ. Influence of human gut microbiome on the healthy and the neurodegenerative aging. Exp Gerontol 2024; 194:112497. [PMID: 38909763 DOI: 10.1016/j.exger.2024.112497] [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: 03/04/2024] [Revised: 05/16/2024] [Accepted: 06/17/2024] [Indexed: 06/25/2024]
Abstract
The gut microbiome plays a crucial role in host health throughout the lifespan by influencing brain function during aging. The microbial diversity of the human gut microbiome decreases during the aging process and, as a consequence, several mechanisms increase, such as oxidative stress, mitochondrial dysfunction, inflammatory response, and microbial gut dysbiosis. Moreover, evidence indicates that aging and neurodegeneration are closely related; consequently, the gut microbiome may serve as a novel marker of lifespan in the elderly. In this narrative study, we investigated how the changes in the composition of the gut microbiome that occur in aging influence to various neuropathological disorders, such as mild cognitive impairment (MCI), dementia, Alzheimer's disease (AD), and Parkinson's disease (PD); and which are the possible mechanisms that govern the relationship between the gut microbiome and cognitive impairment. In addition, several studies suggest that the gut microbiome may be a potential novel target to improve hallmarks of brain aging and to promote healthy cognition; therefore, current and future therapeutic interventions have been also reviewed.
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Affiliation(s)
- Alejandro Borrego-Ruiz
- Departamento de Psicología Social y de las Organizaciones, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain
| | - Juan J Borrego
- Departamento de Microbiología, Universidad de Málaga, Málaga, Spain; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA, Plataforma BIONAND, Málaga, Spain.
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28
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Ghosh S, Nguyen MT, Choi HE, Stahl M, Kühn AL, Van der Auwera S, Grabe HJ, Völzke H, Homuth G, Myers SA, Hogaboam CM, Noth I, Martinez FJ, Petsko GA, Glimcher LH. RIOK2 transcriptionally regulates TRiC and dyskerin complexes to prevent telomere shortening. Nat Commun 2024; 15:7138. [PMID: 39164231 PMCID: PMC11335878 DOI: 10.1038/s41467-024-51336-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 08/02/2024] [Indexed: 08/22/2024] Open
Abstract
Telomere shortening is a prominent hallmark of aging and is emerging as a characteristic feature of Myelodysplastic Syndromes (MDS) and Idiopathic Pulmonary Fibrosis (IPF). Optimal telomerase activity prevents progressive shortening of telomeres that triggers DNA damage responses. However, the upstream regulation of telomerase holoenzyme components remains poorly defined. Here, we identify RIOK2, a master regulator of human blood cell development, as a critical transcription factor for telomere maintenance. Mechanistically, loss of RIOK2 or its DNA-binding/transactivation properties downregulates mRNA expression of both TRiC and dyskerin complex subunits that impairs telomerase activity, thereby causing telomere shortening. We further show that RIOK2 expression is diminished in aged individuals and IPF patients, and it strongly correlates with shortened telomeres in MDS patient-derived bone marrow cells. Importantly, ectopic expression of RIOK2 alleviates telomere shortening in IPF patient-derived primary lung fibroblasts. Hence, increasing RIOK2 levels prevents telomere shortening, thus offering therapeutic strategies for telomere biology disorders.
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Affiliation(s)
- Shrestha Ghosh
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
- Department of Immunology, Harvard Medical School, Boston, MA, USA.
| | - Mileena T Nguyen
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
- Yale University, New Haven, CT, USA
| | - Ha Eun Choi
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Maximilian Stahl
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Annemarie Luise Kühn
- Department for Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
| | - Sandra Van der Auwera
- Department for Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
- German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany
| | - Hans J Grabe
- Department for Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
- German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany
| | - Henry Völzke
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, Germany
| | - Georg Homuth
- Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
| | | | - Cory M Hogaboam
- Women's Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Imre Noth
- Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VA, USA
| | - Fernando J Martinez
- Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Gregory A Petsko
- Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Laurie H Glimcher
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
- Department of Immunology, Harvard Medical School, Boston, MA, USA.
- Department of Medicine, Harvard Medical School, Boston, MA, USA.
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29
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Papageorgakopoulou MA, Bania A, Lagogianni IA, Birmpas K, Assimakopoulou M. The Role of Glia Telomere Dysfunction in the Pathogenesis of Central Nervous System Diseases. Mol Neurobiol 2024; 61:5868-5881. [PMID: 38240992 PMCID: PMC11249767 DOI: 10.1007/s12035-024-03947-6] [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: 10/10/2023] [Accepted: 01/09/2024] [Indexed: 07/16/2024]
Abstract
Maintaining the telomere length is decisive for the viability and homeostasis process of all the cells of an organism, including human glial cells. Telomere shortening of microglial cells has been widely associated with the onset and progression of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Additionally, traumatic brain injury appears to have a positive correlation with the telomere-shortening process of microglia, and telomere length can be used as a non-invasive biomarker for the clinical management of these patients. Moreover, telomere involvement through telomerase reactivation and homologous recombination also known as the alternative lengthening of telomeres (ALT) has been described in gliomagenesis pathways, and particular focus has been given in the translational significance of these mechanisms in gliomas diagnosis and prognostic classification. Finally, glia telomere shortening is implicated in some psychiatric diseases. Given that telomere dysfunction of glial cells is involved in the central nervous system (CNS) disease pathogenesis, it represents a promising drug target that could lead to the incorporation of new tools in the medicinal arsenal for the management of so far incurable conditions.
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Affiliation(s)
| | - Angelina Bania
- School of Medicine, University of Patras, 26504, Patras, Greece
| | | | | | - Martha Assimakopoulou
- Department of Anatomy, Histology and Embryology, School of Medicine, University of Patras, Preclinical Medicine Department Building, 1 Asklipiou, 26504, Patras, Greece.
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30
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Huo S, Tang X, Chen W, Gan D, Guo H, Yao Q, Liao R, Huang T, Wu J, Yang J, Xiao G, Han X. Epigenetic regulations of cellular senescence in osteoporosis. Ageing Res Rev 2024; 99:102235. [PMID: 38367814 DOI: 10.1016/j.arr.2024.102235] [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: 09/18/2023] [Revised: 01/27/2024] [Accepted: 02/13/2024] [Indexed: 02/19/2024]
Abstract
Osteoporosis (OP) is a prevalent age-related disease that is characterized by a decrease in bone mineral density (BMD) and systemic bone microarchitectural disorders. With age, senescent cells accumulate and exhibit the senescence-associated secretory phenotype (SASP) in bone tissue, leading to the imbalance of bone homeostasis, osteopenia, changes in trabecular bone structure, and increased bone fragility. Cellular senescence in the bone microenvironment involves osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells (BMSCs), whose effects on bone homeostasis are regulated by epigenetics. Therefore, the epigenetic regulatory mechanisms of cellular senescence have received considerable attention as potential targets for preventing and treating osteoporosis. In this paper, we systematically review the mechanisms of aging-associated epigenetic regulation in osteoporosis, emphasizing the impact of epigenetics on cellular senescence, and summarize three current methods of targeting cellular senescence, which is helpful better to understand the pathogenic mechanisms of cellular senescence in osteoporosis and provides strategies for the development of epigenetic drugs for the treatment of osteoporosis.
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Affiliation(s)
- Shaochuan Huo
- Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, China; Shenzhen Research Institute of Guangzhou University of Traditional Medicine (Futian), Shenzhen 518000, China
| | - Xinzheng Tang
- Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, China; Shenzhen Research Institute of Guangzhou University of Traditional Medicine (Futian), Shenzhen 518000, China
| | - Weijian Chen
- Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Donghao Gan
- Department of Biochemistry, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen 518055, China
| | - Hai Guo
- Liuzhou Traditional Chinese Medicine Hospital (Liuzhou Zhuang Medical Hospital), Liuzhou 545001, China
| | - Qing Yao
- Department of Biochemistry, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen 518055, China
| | - Rongdong Liao
- Department of Orthopaedics, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Tingting Huang
- Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Junxian Wu
- Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, China
| | - Junxing Yang
- Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, China; Shenzhen Research Institute of Guangzhou University of Traditional Medicine (Futian), Shenzhen 518000, China.
| | - Guozhi Xiao
- Department of Biochemistry, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen 518055, China.
| | - Xia Han
- Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen 518000, China; Shenzhen Research Institute of Guangzhou University of Traditional Medicine (Futian), Shenzhen 518000, China.
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31
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Souza MRD, Garcia ALH, Dalberto D, Picinini J, Touguinha LBA, Salvador M, da Silva J. Multiple factors influence telomere length and DNA damage in individuals environmentally exposed to a coal-burning power plant. MUTATION RESEARCH. GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2024; 898:503793. [PMID: 39147445 DOI: 10.1016/j.mrgentox.2024.503793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 06/27/2024] [Accepted: 07/04/2024] [Indexed: 08/17/2024]
Abstract
Coal is a mixture of several chemicals, many of which have mutagenic and carcinogenic effects and are a key contributor to the global burden of mortality and disease. Previous studies suggest that coal is related to telomeric shortening in individuals occupationally exposed, however little is known about the effects of mining and burning coal on the telomeres of individuals living nearby. Therefore, the primary objective of this investigation was to assess the impact of proximity to coal power plants and coal mines on the genomic instability of individuals environmentally exposed, while also exploring potential associations with individual characteristics, oxidative stress, inflammatory responses, and the presence of inorganic elements. This study involved 80 men participants from three cities around a thermoelectric power plant and one city unexposed to coal and byproducts. DNA was extracted from peripheral blood samples obtained from each participant, and the telomeres length (TL) was assessed using quantitative real-time polymerase chain reaction (qPCR) methodology. No significant difference was observed between exposed individuals (6227 ± 2884 bp) when compared to the unexposed group (5638 ± 2452 bp). Nevertheless, TL decrease was associated with age and risk for cardiovascular disease; and longer TL was found to be linked with increased concentrations of silicon and phosphorus in blood samples. No correlations were observed between TL with comet assay (visual score), micronucleus test, oxidative stress, and inflammatory results. Additional research is required to ascertain the potential correlation between these changes and the onset of diseases and premature mortality.
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Affiliation(s)
- Melissa Rosa de Souza
- Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA) and LaSalle University (UniLaSalle), Avenida Farroupilha, 8001 Bairro São José, Canoas, RS CEP 92425-900, Brazil.
| | - Ana Letícia Hilário Garcia
- Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA) and LaSalle University (UniLaSalle), Avenida Farroupilha, 8001 Bairro São José, Canoas, RS CEP 92425-900, Brazil
| | - Daiana Dalberto
- Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA) and LaSalle University (UniLaSalle), Avenida Farroupilha, 8001 Bairro São José, Canoas, RS CEP 92425-900, Brazil
| | - Juliana Picinini
- Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA) and LaSalle University (UniLaSalle), Avenida Farroupilha, 8001 Bairro São José, Canoas, RS CEP 92425-900, Brazil
| | | | - Mirian Salvador
- Laboratory of Oxidative Stress and Antioxidants, Institute of Biotechnology, University of Caxias do Sul (UCS), Caxias do Sul, RS, Brazil
| | - Juliana da Silva
- Laboratory of Genetic Toxicology, Lutheran University of Brazil (ULBRA) and LaSalle University (UniLaSalle), Avenida Farroupilha, 8001 Bairro São José, Canoas, RS CEP 92425-900, Brazil.
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32
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Yusri K, Kumar S, Fong S, Gruber J, Sorrentino V. Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks. Int J Mol Sci 2024; 25:6793. [PMID: 38928497 PMCID: PMC11203944 DOI: 10.3390/ijms25126793] [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: 05/23/2024] [Revised: 06/16/2024] [Accepted: 06/18/2024] [Indexed: 06/28/2024] Open
Abstract
Aging is a complex and time-dependent decline in physiological function that affects most organisms, leading to increased risk of age-related diseases. Investigating the molecular underpinnings of aging is crucial to identify geroprotectors, precisely quantify biological age, and propose healthy longevity approaches. This review explores pathways that are currently being investigated as intervention targets and aging biomarkers spanning molecular, cellular, and systemic dimensions. Interventions that target these hallmarks may ameliorate the aging process, with some progressing to clinical trials. Biomarkers of these hallmarks are used to estimate biological aging and risk of aging-associated disease. Utilizing aging biomarkers, biological aging clocks can be constructed that predict a state of abnormal aging, age-related diseases, and increased mortality. Biological age estimation can therefore provide the basis for a fine-grained risk stratification by predicting all-cause mortality well ahead of the onset of specific diseases, thus offering a window for intervention. Yet, despite technological advancements, challenges persist due to individual variability and the dynamic nature of these biomarkers. Addressing this requires longitudinal studies for robust biomarker identification. Overall, utilizing the hallmarks of aging to discover new drug targets and develop new biomarkers opens new frontiers in medicine. Prospects involve multi-omics integration, machine learning, and personalized approaches for targeted interventions, promising a healthier aging population.
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Affiliation(s)
- Khalishah Yusri
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Sanjay Kumar
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Sheng Fong
- Department of Geriatric Medicine, Singapore General Hospital, Singapore 169608, Singapore
- Clinical and Translational Sciences PhD Program, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Jan Gruber
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Science Division, Yale-NUS College, Singapore 138527, Singapore
| | - Vincenzo Sorrentino
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
- Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Department of Medical Biochemistry, Amsterdam UMC, Amsterdam Gastroenterology Endocrinology Metabolism and Amsterdam Neuroscience Cellular & Molecular Mechanisms, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands
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Li Y, Tian X, Luo J, Bao T, Wang S, Wu X. Molecular mechanisms of aging and anti-aging strategies. Cell Commun Signal 2024; 22:285. [PMID: 38790068 PMCID: PMC11118732 DOI: 10.1186/s12964-024-01663-1] [Citation(s) in RCA: 42] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 05/15/2024] [Indexed: 05/26/2024] Open
Abstract
Aging is a complex and multifaceted process involving a variety of interrelated molecular mechanisms and cellular systems. Phenotypically, the biological aging process is accompanied by a gradual loss of cellular function and the systemic deterioration of multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that aging is closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, loss of nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, loss of protein balance, deregulated nutrient sensing, altered intercellular communication, and dysbiosis. These age-related changes may be alleviated by intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, and targeted longevity genes. In this review, we summarise the key historical progress in the exploration of important causes of aging and anti-aging strategies in recent decades, which provides a basis for further understanding of the reversibility of aging phenotypes, the application prospect of synthetic biotechnology in anti-aging therapy is also prospected.
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Affiliation(s)
- Yumeng Li
- Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences; National Center of Technology Innovation for Synthetic Biology, Tianjin, China
| | - Xutong Tian
- Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences; National Center of Technology Innovation for Synthetic Biology, Tianjin, China
| | - Juyue Luo
- Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences; National Center of Technology Innovation for Synthetic Biology, Tianjin, China
| | - Tongtong Bao
- Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences; National Center of Technology Innovation for Synthetic Biology, Tianjin, China
| | - Shujin Wang
- Institute of Life Sciences, Chongqing Medical University, Chongqing, China
| | - Xin Wu
- Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences; National Center of Technology Innovation for Synthetic Biology, Tianjin, China.
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Arellano MYG, VanHeest M, Emmadi S, Abdul-Hafez A, Ibrahim SA, Thiruvenkataramani RP, Teleb RS, Omar H, Kesaraju T, Mohamed T, Madhukar BV, Omar SA. Role of Mesenchymal Stem/Stromal Cells (MSCs) and MSC-Derived Extracellular Vesicles (EVs) in Prevention of Telomere Length Shortening, Cellular Senescence, and Accelerated Biological Aging. Bioengineering (Basel) 2024; 11:524. [PMID: 38927760 PMCID: PMC11200821 DOI: 10.3390/bioengineering11060524] [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: 03/19/2024] [Revised: 05/11/2024] [Accepted: 05/13/2024] [Indexed: 06/28/2024] Open
Abstract
Biological aging is defined as a progressive decline in tissue function that eventually results in cell death. Accelerated biologic aging results when the telomere length is shortened prematurely secondary to damage from biological or environmental stressors, leading to a defective reparative mechanism. Stem cells therapy may have a potential role in influencing (counteract/ameliorate) biological aging and maintaining the function of the organism. Mesenchymal stem cells, also called mesenchymal stromal cells (MSCs) are multipotent stem cells of mesodermal origin that can differentiate into other types of cells, such as adipocytes, chondrocytes, and osteocytes. MSCs influence resident cells through the secretion of paracrine bioactive components such as cytokines and extracellular vesicles (EVs). This review examines the changes in telomere length, cellular senescence, and normal biological age, as well as the factors contributing to telomere shortening and accelerated biological aging. The role of MSCs-especially those derived from gestational tissues-in prevention of telomere shortening (TS) and accelerated biological aging is explored. In addition, the strategies to prevent MSC senescence and improve the antiaging therapeutic application of MSCs and MSC-derived EVs in influencing telomere length and cellular senescence are reviewed.
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Affiliation(s)
- Myrna Y. Gonzalez Arellano
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.Y.G.A.); (A.A.-H.); (S.A.I.); (R.P.T.); (R.S.T.); (H.O.); (T.K.); (T.M.); (B.V.M.)
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.V.); (S.E.)
- Regional Neonatal Intensive Care Unit, Sparrow Hospital, Lansing, MI 48912, USA
| | - Matthew VanHeest
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.V.); (S.E.)
| | - Sravya Emmadi
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.V.); (S.E.)
| | - Amal Abdul-Hafez
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.Y.G.A.); (A.A.-H.); (S.A.I.); (R.P.T.); (R.S.T.); (H.O.); (T.K.); (T.M.); (B.V.M.)
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.V.); (S.E.)
| | - Sherif Abdelfattah Ibrahim
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.Y.G.A.); (A.A.-H.); (S.A.I.); (R.P.T.); (R.S.T.); (H.O.); (T.K.); (T.M.); (B.V.M.)
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.V.); (S.E.)
- Histology and Cell Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Ranga P. Thiruvenkataramani
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.Y.G.A.); (A.A.-H.); (S.A.I.); (R.P.T.); (R.S.T.); (H.O.); (T.K.); (T.M.); (B.V.M.)
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.V.); (S.E.)
- Regional Neonatal Intensive Care Unit, Sparrow Hospital, Lansing, MI 48912, USA
| | - Rasha S. Teleb
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.Y.G.A.); (A.A.-H.); (S.A.I.); (R.P.T.); (R.S.T.); (H.O.); (T.K.); (T.M.); (B.V.M.)
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.V.); (S.E.)
- Department of Pediatrics and Neonatology, Qena Faculty of Medicine, South Valley University, Qena 83523, Egypt
| | - Hady Omar
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.Y.G.A.); (A.A.-H.); (S.A.I.); (R.P.T.); (R.S.T.); (H.O.); (T.K.); (T.M.); (B.V.M.)
| | - Tulasi Kesaraju
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.Y.G.A.); (A.A.-H.); (S.A.I.); (R.P.T.); (R.S.T.); (H.O.); (T.K.); (T.M.); (B.V.M.)
| | - Tarek Mohamed
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.Y.G.A.); (A.A.-H.); (S.A.I.); (R.P.T.); (R.S.T.); (H.O.); (T.K.); (T.M.); (B.V.M.)
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.V.); (S.E.)
- Regional Neonatal Intensive Care Unit, Sparrow Hospital, Lansing, MI 48912, USA
| | - Burra V. Madhukar
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.Y.G.A.); (A.A.-H.); (S.A.I.); (R.P.T.); (R.S.T.); (H.O.); (T.K.); (T.M.); (B.V.M.)
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.V.); (S.E.)
| | - Said A. Omar
- Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.Y.G.A.); (A.A.-H.); (S.A.I.); (R.P.T.); (R.S.T.); (H.O.); (T.K.); (T.M.); (B.V.M.)
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA; (M.V.); (S.E.)
- Regional Neonatal Intensive Care Unit, Sparrow Hospital, Lansing, MI 48912, USA
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Bao L, Zhou Y, Shu J, Li H, Xi S, Xu M, Cai Q, Dai X, Zeng Y, Zeng F. Impact of telomere length and mitochondrial DNA copy number variants on survival of newborn cloned calves. Theriogenology 2024; 225:1-8. [PMID: 38781848 DOI: 10.1016/j.theriogenology.2024.05.019] [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: 12/18/2023] [Revised: 04/16/2024] [Accepted: 05/15/2024] [Indexed: 05/25/2024]
Abstract
An established technology to create cloned animals is through the use of somatic cell nuclear transfer (SCNT), in which reprogramming the somatic cell nucleus to a totipotent state by enucleated oocyte cytoplasm is a necessary process, including telomere length reprogramming. The limitation of this technology; however, is that the live birth rate of offspring produced through SCNT is significantly lower than that of IVF. Whether and how telomere length play a role in the development of cloned animals is not well understood. Only a few studies have evaluated this association in cloned mice, and fewer still in cloned cows. In this study, we investigated the difference in telomere length as well as the abundance of some selected molecules between newborn deceased cloned calves and normal cows of different ages either produced by SCNT or via natural conception, in order to evaluate the association between telomere length and abnormal development of cloned cows. The absolute telomere length and relative mitochondrial DNA (mtDNA) copy number were determined by real-time quantitative PCR (qPCR), telomere related gene abundance by reverse-transcription quantitative PCR (RT-qPCR), and senescence-associated β-galactosidase (SA-β-gal) expression by SA-β-gal staining. The results demonstrate that the newborn deceased SCNT calves had significantly shortened telomere lengths compared to newborn naturally conceived calves and newborn normal SCNT calves. Significantly lower mtDNA copy number, and significantly lower relative abundance of LMNB1 and TERT, higher relative abundance of CDKN1A, and aberrant SA-β-gal expression were observed in the newborn deceased SCNT calves, consistent with the change in telomere length. These results demonstrate that abnormal telomere shortening, lower mtDNA copy number and abnormal abundance of related genes were specific to newborn deceased SCNT calves, suggesting that abnormally short telomere length may be associated with abnormal development in the cloned calves.
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Affiliation(s)
- Liwen Bao
- Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China
| | - Yiye Zhou
- Department of Histo-Embryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, 200040, China
| | - Juan Shu
- Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, 200040, China
| | - Hua Li
- Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, 200040, China
| | - Shubin Xi
- Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, 200040, China
| | - Miao Xu
- Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, 200040, China
| | - Qin Cai
- Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, 200040, China
| | - Xiuqin Dai
- Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, 200040, China
| | - Yitao Zeng
- Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, 200040, China
| | - Fanyi Zeng
- Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China; Department of Histo-Embryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health and Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai, 200040, China; School of Pharmacy, Macau University of Science and Technology, Macau, China.
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Basyal D, Lee S, Kim HJ. Antioxidants and Mechanistic Insights for Managing Dry Age-Related Macular Degeneration. Antioxidants (Basel) 2024; 13:568. [PMID: 38790673 PMCID: PMC11117704 DOI: 10.3390/antiox13050568] [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: 03/18/2024] [Revised: 04/26/2024] [Accepted: 05/02/2024] [Indexed: 05/26/2024] Open
Abstract
Age-related macular degeneration (AMD) severely affects central vision due to progressive macular degeneration and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging is considered an important contributor to AMD pathogenesis despite multifaceted risk factors including genetic predisposition and environmental agents. Wet AMD can be managed with routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for the successful management of the dry form. The toxic carbonyls due to photo-oxidative degradation of accumulated bisretinoids within lysosomes initiate a series of events including protein adduct formation, impaired autophagy flux, complement activation, and chronic inflammation, which is implicated in dry AMD. Therapy based on antioxidants has been extensively studied for its promising effect in reducing the impact of oxidative stress. This paper reviews the dry AMD pathogenesis, delineates the effectiveness of dietary and nutrition supplements in clinical studies, and explores pre-clinical studies of antioxidant molecules, extracts, and formulations with their mechanistic insights.
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Affiliation(s)
| | | | - Hye Jin Kim
- College of Pharmacy, Keimyung University, Dauge 42601, Republic of Korea
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Gupta M, Rathored J. Hyperbaric oxygen therapy: future prospects in regenerative therapy and anti-aging. FRONTIERS IN AGING 2024; 5:1368982. [PMID: 38757145 PMCID: PMC11097100 DOI: 10.3389/fragi.2024.1368982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 04/12/2024] [Indexed: 05/18/2024]
Abstract
Hyperbaric Oxygen Therapy (HBOT) utilizes 100% oxygen at high atmospheric pressure for clinical applications. HBOT has proven to be an effective supplementary treatment for a variety of clinical and pathological disorders. HBOT's therapeutic results are based on the physiological effects of increased tissue oxygenation, or improved oxygen bioavailability. HBOT's current indications in illnesses like as wound healing, thermal or radiation burns, and tissue necrosis point to its function in facilitating the regeneration process. Various research has revealed that HBOT plays a function in vascularization, angiogenesis, and collagen production augmentation. Individual regeneration capacity is influenced by both environmental and genetic factors. Furthermore, the regenerating ability of different types of tissues varies, and this ability declines with age. HBOT affects physiological processes at the genetic level by altering gene expression, delaying cell senescence, and assisting in telomere length enhancement. The positive results in a variety of indications, ranging from tissue regeneration to better cognitive function, indicate that it has enormous potential in regenerative and anti-aging therapy.
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Affiliation(s)
- Manoj Gupta
- Datta Meghe Institute of Medical Sciences, Wardha, India
| | - Jaishriram Rathored
- Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, India
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Zhang Y, Zhu Y, Zhang X, Li C, Fu H, Lin L, Yang Z, Zhang B. The association of sleep duration and leukocyte telomere length in middle-aged and young-old adults: A cross-sectional study of UK Biobank. Sleep Med 2024; 117:18-24. [PMID: 38493659 DOI: 10.1016/j.sleep.2024.02.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/28/2024] [Accepted: 02/28/2024] [Indexed: 03/19/2024]
Abstract
BACKGROUND The relationships between sleep duration and aging-associated diseases are intricate. Leukocyte telomere length (LTL) is a biomarker of aging, while the association of sleep duration and LTL is unclear. METHODS The 310,091 study participants from UK Biobank were enrolled in this cross-sectional study. Restricted cubic splines (RCS) analysis was firstly performed to assess the nonlinear relationship between sleep duration and LTL. Sleep duration was then categorized into three groups: <7 h (short sleep duration), 7-8 h (reference group), and >8 h (long sleep duration) and multiple linear regression was applied to analyze the association of short sleep and long sleep duration with LTL. We further performed subgroup analyses stratified by sex, age, chronotype and snoring. RESULTS RCS showed an inverted J-shaped relationship between sleep duration and LTL. Compared with the reference group, the inverse association of long sleep duration and LTL was statistically significant in fully-adjusted model (P = 0.001). Subgroup analyses showed that this association was more apparent in people over 50 years (51-60 y: P = 0.002; >60 y: P = 0.005), in men (P = 0.022), and in people preferred evening chronotype (P = 0.001). CONCLUSION Compared with participants sleeping 7-8 h, those sleep longer than 8 h had shorter LTL in middle-aged and young-old adults. The negative association between long sleep duration and LTL was more apparent in older people, in men, and in people preferred evening chronotype.
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Affiliation(s)
- Yuchun Zhang
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, 510515, PR China
| | - Yuanting Zhu
- Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China; NHC Key Laboratory on Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China
| | - Xiaojun Zhang
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, 510515, PR China
| | - Chunhao Li
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, 510515, PR China
| | - Hongna Fu
- NHC Key Laboratory on Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Department of Emergency, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Luyang Lin
- NHC Key Laboratory on Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Department of Emergency, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China
| | - Zhen Yang
- Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China; NHC Key Laboratory on Assisted Circulation (Sun Yat-sen University), Guangzhou, 510080, PR China; Department of Emergency, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China.
| | - Bo Zhang
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, 510515, PR China.
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Yan X, Yang P, Li Y, Liu T, Zha Y, Wang T, Zhang J, Feng Z, Li M. New insights from bidirectional Mendelian randomization: causal relationships between telomere length and mitochondrial DNA copy number in aging biomarkers. Aging (Albany NY) 2024; 16:7387-7404. [PMID: 38663933 PMCID: PMC11087129 DOI: 10.18632/aging.205765] [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: 01/08/2024] [Accepted: 03/28/2024] [Indexed: 05/08/2024]
Abstract
Mitochondrial DNA (mtDNA) copy number and telomere length (TL) are dynamic factors that have been linked to the aging process in organisms. However, the causal relationship between these variables remains uncertain. In this research, instrumental variables (IVs) related to mtDNA copy number and TL were obtained from publicly available genome-wide association studies (GWAS). Through bidirectional Mendelian randomization (MR) analysis, we examined the potential causal relationship between these factors. The forward analysis, with mtDNA copy number as the exposure and TL as the outcome, did not reveal a significant effect (B=-0.004, P>0.05). On the contrary, upon conducting a reverse analysis, it was found that there exists a positive causal relationship (B=0.054, P<0.05). Sensitivity analyses further confirmed the reliability of these results. The outcomes of this study indicate a one-way positive causal relationship, indicating that telomere shortening in the aging process may lead to a decrease in mtDNA copy number, providing new perspectives on their biological mechanisms.
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Affiliation(s)
- Xinyu Yan
- Zhongshan City People’s Hospital, Xinxiang Medical University, Xinxiang 453003, Henan, China
| | - Peixuan Yang
- Zhongshan City People’s Hospital, Xinxiang Medical University, Xinxiang 453003, Henan, China
| | - Yani Li
- Department of Radiation Oncology, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, China
| | - Ting Liu
- Department of Radiation Oncology, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, China
| | - Yawen Zha
- Department of Radiation Oncology, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, China
| | - Ting Wang
- Department of Radiation Oncology, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, China
| | - Jingjing Zhang
- Department of Radiation Oncology, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, China
| | - Zhijun Feng
- Department of Radiation Oncology, Jiangmen Central Hospital, Jiangmen 529000, Guangdong, China
| | - Minying Li
- Department of Radiation Oncology, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, China
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He X, Gao X, Xie W. Research Progress in Skin Aging and Immunity. Int J Mol Sci 2024; 25:4101. [PMID: 38612909 PMCID: PMC11012511 DOI: 10.3390/ijms25074101] [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: 03/18/2024] [Revised: 04/02/2024] [Accepted: 04/06/2024] [Indexed: 04/14/2024] Open
Abstract
Skin aging is a complex process involving structural and functional changes and is characterized by a decrease in collagen content, reduced skin thickness, dryness, and the formation of wrinkles. This process is underpinned by multiple mechanisms including the free radical theory, inflammation theory, photoaging theory, and metabolic theory. The skin immune system, an indispensable part of the body's defense mechanism, comprises macrophages, lymphocytes, dendritic cells, and mast cells. These cells play a pivotal role in maintaining skin homeostasis and responding to injury or infection. As age advances, along with various internal and external environmental stimuli, skin immune cells may undergo senescence or accelerated aging, characterized by reduced cell division capability, increased mortality, changes in gene expression patterns and signaling pathways, and altered immune cell functions. These changes collectively impact the overall function of the immune system. This review summarizes the relationship between skin aging and immunity and explores the characteristics of skin aging, the composition and function of the skin immune system, the aging of immune cells, and the effects of these cells on immune function and skin aging. Immune dysfunction plays a significant role in skin aging, suggesting that immunoregulation may become one of the important strategies for the prevention and treatment of skin aging.
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Affiliation(s)
- Xin He
- State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; (X.H.); (X.G.)
- Open FIESTA Center, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
- Shenzhen Key Laboratory of Health Science and Technology, Institute of Biopharmaceutical and Health, Tsinghua University, Shenzhen 518055, China
| | - Xinyu Gao
- State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; (X.H.); (X.G.)
- Shenzhen Key Laboratory of Health Science and Technology, Institute of Biopharmaceutical and Health, Tsinghua University, Shenzhen 518055, China
| | - Weidong Xie
- State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China; (X.H.); (X.G.)
- Open FIESTA Center, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
- Shenzhen Key Laboratory of Health Science and Technology, Institute of Biopharmaceutical and Health, Tsinghua University, Shenzhen 518055, China
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Xu L, Yang T, Wen M, Wen D, Jin C, An M, Wang L, Liu Y, Fan J. Frontiers in the Etiology and Treatment of Preterm Premature Rupture of Membrane: From Molecular Mechanisms to Innovative Therapeutic Strategies. Reprod Sci 2024; 31:917-931. [PMID: 37989803 DOI: 10.1007/s43032-023-01411-9] [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: 09/20/2023] [Accepted: 11/09/2023] [Indexed: 11/23/2023]
Abstract
Preterm premature rupture of membranes (pPROM) poses a significant threat to fetal viability and increases the risk for newborn morbidities. The perinatal period of preterm infants affected by pPROM is often characterized by higher rates of mortality and morbidity, with associated risks of cerebral palsy, developmental delays, compromised immune function, respiratory diseases, and sensory impairments. pPROM is believed to result from a variety of causes, including but not limited to microbially induced infections, stretching of fetal membranes, oxidative stress, inflammatory responses, and age-related changes in the fetal-placental interface. Maternal stress, nutritional deficiencies, and medically induced procedures such as fetoscopy are also considered potential contributing factors to pPROM. This comprehensive review explores the potential etiologies leading to pPROM, delves into the intricate molecular mechanisms through which these etiologies cause membrane ruptures, and provides a concise overview of diagnostic and treatment approaches for pPROM. Based on available therapeutic options, this review proposes and explores the possibilities of utilizing a novel composite hydrogel composed of amniotic membrane particles for repairing ruptured fetal membranes, thereby holding promise for its clinical application.
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Affiliation(s)
- Ludan Xu
- Institute of Biomedical Engineering, College of Biomedical Engineering, Shanxi Key Laboratory of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan, Shanxi, China
| | - Tiantian Yang
- Institute of Biomedical Engineering, College of Biomedical Engineering, Shanxi Key Laboratory of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan, Shanxi, China
| | - Meiling Wen
- Institute of Biomedical Engineering, College of Biomedical Engineering, Shanxi Key Laboratory of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan, Shanxi, China
- Research Center for Nanobiomaterials & Regenerative Medicine, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan, Shanxi, China
| | - Dawei Wen
- Institute of Biomedical Engineering, College of Biomedical Engineering, Shanxi Key Laboratory of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan, Shanxi, China
| | - Chaoyang Jin
- Institute of Biomedical Engineering, College of Biomedical Engineering, Shanxi Key Laboratory of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan, Shanxi, China
| | - Meiwen An
- Institute of Biomedical Engineering, College of Biomedical Engineering, Shanxi Key Laboratory of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan, Shanxi, China
| | - Li Wang
- Institute of Biomedical Engineering, College of Biomedical Engineering, Shanxi Key Laboratory of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan, Shanxi, China
| | - Yang Liu
- Institute of Biomedical Engineering, College of Biomedical Engineering, Shanxi Key Laboratory of Material Strength & Structural Impact, Taiyuan University of Technology, Taiyuan, Shanxi, China.
- Research Center for Nanobiomaterials & Regenerative Medicine, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan, Shanxi, China.
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
| | - Junmei Fan
- Department of Reproductive Medicine Center, Children's Hospital of Shanxi and Women Health Center of Shanxi, Affiliated of Shanxi Medical University, Taiyuan, Shanxi, China.
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Zhao L, Jin W, Zhang T, Lu Y, Liu Q, Cai J, Luo L, Teng K, Guan Q, Wu S, Rong J, Liang YJ, Cao J, Qin L, Huang C, Wang X, Li Y, Zhang Z, Qin J. Association between the dietary antioxidant index and relative telomere length of leucocytes in the Chinese population. Br J Nutr 2024; 131:1031-1040. [PMID: 37926899 DOI: 10.1017/s0007114523002544] [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] [Indexed: 11/07/2023]
Abstract
Dietary antioxidant indices (DAI) may be potentially associated with relative telomere length (RTL) of leucocytes. This study aimed to investigate the relationship between DAI and RTL. A cross-sectional study involving 1656 participants was conducted. A generalised linear regression model and a restricted cubic spline model were used to assess the correlation of DAI and its components with RTL. Generalised linear regression analysis revealed that DAI (β = 0·005, P = 0·002) and the intake of its constituents vitamin C (β = 0·043, P = 0·027), vitamin E (β = 0·088, P < 0·001), Se (β = 0·075, P = 0·003), and Zn (β = 0·075, P = 0·023) were significantly and positively correlated with RTL. Sex-stratified analysis showed that DAI (β = 0·006, P = 0·005) and its constituents vitamin E (β = 0·083, P = 0·012), Se (β = 0·093, P = 0·006), and Zn (β = 0·092, P = 0·034) were significantly and positively correlated with RTL among females. Meanwhile, among males, only vitamin E intake (β = 0·089, P = 0·013) was significantly and positively associated with RTL. Restricted cubic spline analysis revealed linear positive associations between DAI and its constituents' (vitamin E, Se and Zn) intake and RTL in the total population. Sex-stratified analysis revealed a linear positive correlation between DAI and its constituents' (vitamin E, Se and Zn) intake and RTL in females. Our study found a significant positive correlation between DAI and RTL, with sex differences.
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Affiliation(s)
- Linhai Zhao
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Wenjia Jin
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Tiantian Zhang
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Yufu Lu
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Qiumei Liu
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Jiansheng Cai
- School of Public Health, Guilin Medical University, Guangxi Zhuang Autonomous Region, Guilin, Guangxi, People's Republic of China
| | - Lei Luo
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Kaisheng Teng
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Qinyi Guan
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Songju Wu
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Jiahui Rong
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Yu Jian Liang
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Jiejing Cao
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Lidong Qin
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Chuwu Huang
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - Xuexiu Wang
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
| | - You Li
- School of Public Health, Guilin Medical University, Guangxi Zhuang Autonomous Region, Guilin, Guangxi, People's Republic of China
| | - Zhiyong Zhang
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
- School of Public Health, Guilin Medical University, Guangxi Zhuang Autonomous Region, Guilin, Guangxi, People's Republic of China
- Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care, Guilin Medical University, Guilin, Guangxi, People's Republic of China
| | - Jian Qin
- Department of Environmental and Occupational Health, Guangxi Medical University, Nanning, Guangxi530021, People's Republic of China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
- Guangxi Key Laboratory of Environment and Health Research, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education
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Li Y, Lai S, Kan X. Causal relationship between immune cells and telomere length: mendelian randomization analysis. BMC Immunol 2024; 25:19. [PMID: 38459464 PMCID: PMC10924351 DOI: 10.1186/s12865-024-00610-6] [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: 11/07/2023] [Accepted: 02/28/2024] [Indexed: 03/10/2024] Open
Abstract
BACKGROUND The causal relationship between immune cells and telomere length remains controversial. METHODS Data on the immune cells were obtained from a previous study with 3,757 participants. Data on telomere length were obtained from the OpenGWAS database. Genome-Wide Association Study (GWAS) data were obtained and screened for eligible instrumental variables (IVs) using the TwoSampleMR package and the Phenoscanner database. To investigate the genetic causality between immune cells and telomere length, Mendelian randomization (MR) analysis and Bayesian weighted Mendelian randomization (BWMR) analysis were used. RESULTS MR analysis showed that there is indeed a genetic causal relationship between immune cells and telomere length. A total of 16 immune cells were successfully validated. A positive correlation was found between telomere length and immune cells such as CD28 + CD45RA + CD8br %CD8br (OR = 1.002, 95%CI: 1.000-1.003). A negative correlation was found between telomere length and immune cells such as Transitional AC (OR = 0.991, 95%CI: 0.984-0.997) (P < 0.05). Reverse MR analysis similarly confirmed that telomere length can affect four types of immune cells, including CD25 on IgD + CD24- (OR = 1.291, 95%CI: 1.060-1.571), at the genetic level. CONCLUSION There is indeed a mutual genetic causality between immune cells and telomere length, which will provide theoretical basis and support for more subsequent clinical studies.
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Affiliation(s)
- Yujian Li
- Department of Pediatrics, General Hospital of Tianjin Medical University, No.154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Shenglin Lai
- Department of Pediatrics, General Hospital of Tianjin Medical University, No.154, Anshan Road, Heping District, Tianjin, 300052, China
| | - Xuan Kan
- Department of Pediatrics, General Hospital of Tianjin Medical University, No.154, Anshan Road, Heping District, Tianjin, 300052, China.
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Zhou G, Chai J, Li Q, Sun P, Wang Y, Wu J, Zhang J, Li Y, Dong W, Zhang C, Yu F, Yan X, Ba Y. U-shaped relationship between ozone exposure and preterm birth risk associated with preconception telomere length. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 344:123366. [PMID: 38242305 DOI: 10.1016/j.envpol.2024.123366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 01/10/2024] [Accepted: 01/14/2024] [Indexed: 01/21/2024]
Abstract
There are conflicting findings regarding the association of ozone (O3) exposure with preterm birth (PTB) occurrence. In the present study, two cohorts were combined to explore the relationship between maternal O3 exposure during pregnancy and PTB risk, and analyze the underlying mechanisms of this relationship in terms of alterations in the preconception telomere length. Cohort 1 included mothers who participated in the National Free Preconception Health Examination Project in Henan Province from 2014 to 2018 along with their newborns (n = 1,066,696). Cohort 2 comprised mothers who conceived between 2016 and 2018 and their newborns (n = 1871) from six areas in Henan Province. The telomere length was assessed in the peripheral blood of mothers at the preconception stage. Data on air pollutant concentrations were collected from environmental monitoring stations and individual exposures were assessed using an inverse distance-weighted model. O3 concentrations (100.60 ± 14.13 μg/m3) were lower in Cohort 1 than in Cohort 2 (114.09 ± 15.17 μg/m3). Linear analyses showed that PTB risk decreased with increasing O3 exposure concentrations in Cohort 1 but increased with increasing O3 exposure concentrations in Cohort 2. Nonlinear analyses revealed that PTB risk tended to decrease and then increase with increasing O3 exposure concentrations in both cohorts. Besides, PTB risk was reduced by 88% for each-unit increase in telomere length in those exposed to moderate O3 concentrations (92.4-123.7 μg/m3, P < 0.05). While no significant association was observed between telomere length and PTB at extreme O3 concentration exposure during entire pregnancy (<92.4 or >123.7 μg/m3, P > 0.05) in Cohort 2. These findings reveal a nonlinear (U-shaped) relationship between O3 exposure and PTB risk. Furthermore, telomere with elevated length was associated with decreased risk of PTB only when exposed to moderate concentrations of O3, but not when exposed to extreme concentrations of O3 during pregnancy.
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Affiliation(s)
- Guoyu Zhou
- Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, China; National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, Henan, China
| | - Jian Chai
- National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, Henan, China; Henan Institute of Reproduction Health Science and Technology, Zhengzhou, Henan, China
| | - Qinyang Li
- Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Panpan Sun
- National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, Henan, China; Henan Institute of Reproduction Health Science and Technology, Zhengzhou, Henan, China
| | - Yalong Wang
- Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Jingjing Wu
- Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Junxi Zhang
- National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, Henan, China; Henan Institute of Reproduction Health Science and Technology, Zhengzhou, Henan, China
| | - Yan Li
- Synergetic Innovation Center of Kinesis and Health, School of Physical Education (Main Campus), Zhengzhou University, Zhengzhou, Henan, China
| | - Wei Dong
- National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, Henan, China; Henan Institute of Reproduction Health Science and Technology, Zhengzhou, Henan, China
| | - Cuican Zhang
- National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, Henan, China; Henan Institute of Reproduction Health Science and Technology, Zhengzhou, Henan, China
| | - Fangfang Yu
- Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Xi Yan
- Department of Neurology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
| | - Yue Ba
- Department of Environmental Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, Henan, China; Yellow River Institute for Ecological Protection & Regional Coordinated Development, Zhengzhou University, Zhengzhou, Henan, China
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Kitaeva KV, Solovyeva VV, Blatt NL, Rizvanov AA. Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies. Int J Mol Sci 2024; 25:643. [PMID: 38203812 PMCID: PMC10778954 DOI: 10.3390/ijms25010643] [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: 11/08/2023] [Revised: 12/21/2023] [Accepted: 12/30/2023] [Indexed: 01/12/2024] Open
Abstract
The improvement of human living conditions has led to an increase in average life expectancy, creating a new social and medical problem-aging, which diminishes the overall quality of human life. The aging process of the body begins with the activation of effector signaling pathways of aging in cells, resulting in the loss of their normal functions and deleterious effects on the microenvironment. This, in turn, leads to chronic inflammation and similar transformations in neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of tissues and organs, ultimately leading to a reduced quality of life and an elevated risk of mortality. Among the most promising methods for addressing aging and age-related illnesses are pharmacological, genetic, and cellular therapies. Elevating the activity of aging-suppressing genes, employing specific groups of native and genetically modified cells, and utilizing senolytic medications may offer the potential to delay aging and age-related ailments over the long term. This review explores strategies and advancements in the field of anti-aging therapies currently under investigation, with a particular emphasis on gene therapy involving adeno-associated vectors and cell-based therapeutic approaches.
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Affiliation(s)
- Kristina V. Kitaeva
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (K.V.K.); (V.V.S.); (N.L.B.)
| | - Valeriya V. Solovyeva
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (K.V.K.); (V.V.S.); (N.L.B.)
| | - Nataliya L. Blatt
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (K.V.K.); (V.V.S.); (N.L.B.)
| | - Albert A. Rizvanov
- Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; (K.V.K.); (V.V.S.); (N.L.B.)
- Division of Medical and Biological Sciences, Tatarstan Academy of Sciences, 420111 Kazan, Russia
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Rasouli M, Naeimzadeh Y, Hashemi N, Hosseinzadeh S. Age-Related Alterations in Mesenchymal Stem Cell Function: Understanding Mechanisms and Seeking Opportunities to Bypass the Cellular Aging. Curr Stem Cell Res Ther 2024; 19:15-32. [PMID: 36642876 DOI: 10.2174/1574888x18666230113144016] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 10/28/2022] [Accepted: 11/23/2022] [Indexed: 01/17/2023]
Abstract
Undoubtedly, mesenchymal stem cells (MSCs) are the most common cell therapy candidates in clinical research and therapy. They not only exert considerable therapeutic effects to alleviate inflammation and promote regeneration, but also show low-immunogenicity properties, which ensure their safety following allogeneic transplantation. Thanks to the necessity of providing a sufficient number of MSCs to achieve clinically efficient outcomes, prolonged in vitro cultivation is indisputable. However, either following long-term in vitro expansion or aging in elderly individuals, MSCs face cellular senescence. Senescent MSCs undergo an impairment in their function and therapeutic capacities and secrete degenerative factors which negatively affect young MSCs. To this end, designing novel investigations to further elucidate cellular senescence and to pave the way toward finding new strategies to reverse senescence is highly demanded. In this review, we will concisely discuss current progress on the detailed mechanisms of MSC senescence and various inflicted changes following aging in MSC. We will also shed light on the examined strategies underlying monitoring and reversing senescence in MSCs to bypass the comprised therapeutic efficacy of the senescent MSCs.
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Affiliation(s)
- Mehdi Rasouli
- Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Yasaman Naeimzadeh
- Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nader Hashemi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Simzar Hosseinzadeh
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Hollands P, Ovokaitys T. New Concepts in the Manipulation of the Aging Process. Curr Stem Cell Res Ther 2024; 19:178-184. [PMID: 36752298 DOI: 10.2174/1574888x18666230208102635] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 12/26/2022] [Accepted: 12/28/2022] [Indexed: 02/09/2023]
Abstract
This review explores the current concepts in aging and then goes on to describe a novel, ground-breaking technology which will change the way we think about and manage aging. The foundation of the review is based on the work carried out on the QiLaser activation of human Very Small Embryonic Like (hVSEL) pluripotent stem cells in autologous Platelet Rich Plasma (PRP), known as the Qigeneration Procedure. The application of this technology in anti-aging technology is discussed with an emphasis on epigenetic changes during aging focusing on DNA methylation.
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Affiliation(s)
- Peter Hollands
- CTO Qigenix, 6125 Paseo Del Norte, Suite 140, Carlsbad, CA 92008, USA
| | - Todd Ovokaitys
- CEO Qigenix, 6125 Paseo Del Norte, Suite 140, Carlsbad, CA 92008, USA
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Zhou J, Tang CK. Cytoplasmic Polyadenylation Element Binding Protein 1 and Atherosclerosis: Prospective Target and New Insights. Curr Vasc Pharmacol 2024; 22:95-105. [PMID: 38284693 DOI: 10.2174/0115701611258090231221082502] [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: 05/12/2023] [Revised: 12/11/2023] [Accepted: 12/12/2023] [Indexed: 01/30/2024]
Abstract
The ribonucleic acid (RNA)-binding protein Cytoplasmic Polyadenylation Element Binding Protein 1 (CPEB1), a key member of the CPEB family, is essential in controlling gene expression involved in both healthy physiological and pathological processes. CPEB1 can bind to the 3'- untranslated regions (UTR) of substrate messenger ribonucleic acid (mRNA) and regulate its translation. There is increasing evidence that CPEB1 is closely related to the pathological basis of atherosclerosis. According to recent investigations, many pathological processes, including inflammation, lipid metabolism, endothelial dysfunction, angiogenesis, oxidative stress, cellular senescence, apoptosis, and insulin resistance, are regulated by CPEB1. This review considers the prevention and treatment of atherosclerotic heart disease in relation to the evolution of the physiological function of CPEB1, recent research breakthroughs, and the potential participation of CPEB1 in atherosclerosis.
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Affiliation(s)
- Jing Zhou
- Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, School of Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Chao-Ke Tang
- Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, School of Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
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Wan R, Wang L, Zhu M, Li W, Duan Y, Yu G. Cellular Senescence: A Troy Horse in Pulmonary Fibrosis. Int J Mol Sci 2023; 24:16410. [PMID: 38003600 PMCID: PMC10671822 DOI: 10.3390/ijms242216410] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 11/07/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023] Open
Abstract
Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by myofibroblast abnormal activation and extracellular matrix deposition. However, the pathogenesis of PF remains unclear, and treatment options are limited. Epidemiological studies have shown that the average age of PF patients is estimated to be over 65 years, and the incidence of the disease increases with age. Therefore, PF is considered an age-related disease. A preliminary study on PF patients demonstrated that the combination therapy of the anti-senescence drugs dasatinib and quercetin improved physical functional indicators. Given the global aging population and the role of cellular senescence in tissue and organ aging, understanding the impact of cellular senescence on PF is of growing interest. This article systematically summarizes the causes and signaling pathways of cellular senescence in PF. It also objectively analyzes the impact of senescence in AECs and fibroblasts on PF development. Furthermore, potential intervention methods targeting cellular senescence in PF treatment are discussed. This review not only provides a strong theoretical foundation for understanding and manipulating cellular senescence, developing new therapies to improve age-related diseases, and extending a healthy lifespan but also offers hope for reversing the toxicity caused by the massive accumulation of senescence cells in humans.
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Affiliation(s)
- Ruyan Wan
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang 453007, China; (R.W.); (L.W.); (M.Z.); (W.L.); (Y.D.)
- State Key Laboratory Cell Differentiation and Regulation, Henan Normal University, Xinxiang 453007, China
| | - Lan Wang
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang 453007, China; (R.W.); (L.W.); (M.Z.); (W.L.); (Y.D.)
- State Key Laboratory Cell Differentiation and Regulation, Henan Normal University, Xinxiang 453007, China
| | - Miaomiao Zhu
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang 453007, China; (R.W.); (L.W.); (M.Z.); (W.L.); (Y.D.)
- State Key Laboratory Cell Differentiation and Regulation, Henan Normal University, Xinxiang 453007, China
| | - Wenwen Li
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang 453007, China; (R.W.); (L.W.); (M.Z.); (W.L.); (Y.D.)
- State Key Laboratory Cell Differentiation and Regulation, Henan Normal University, Xinxiang 453007, China
| | - Yudi Duan
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang 453007, China; (R.W.); (L.W.); (M.Z.); (W.L.); (Y.D.)
- State Key Laboratory Cell Differentiation and Regulation, Henan Normal University, Xinxiang 453007, China
| | - Guoying Yu
- Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang 453007, China; (R.W.); (L.W.); (M.Z.); (W.L.); (Y.D.)
- State Key Laboratory Cell Differentiation and Regulation, Henan Normal University, Xinxiang 453007, China
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Sapozhnikova YP, Koroleva AG, Yakhnenko VM, Volkova AA, Avezova TN, Glyzina OY, Sakirko MV, Tolstikova LI, Sukhanova LV. Thermal Preconditioning Alters the Stability of Hump-Snout Whitefish ( Coregonus fluviatilis) and Its Hybrid Form, Showing Potential for Aquaculture. BIOLOGY 2023; 12:1348. [PMID: 37887058 PMCID: PMC10603914 DOI: 10.3390/biology12101348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/16/2023] [Accepted: 10/18/2023] [Indexed: 10/28/2023]
Abstract
One of the little-studied ways that climate warming or temperature increases in aquaculture could affect aquatic animals is through accelerated aging. This study is dedicated to understanding the principles of molecular and cellular aging in the target tissues of juvenile whitefishes (Yenisei hump-snout whitefish and its hybrid) under the influence of acute heat stress (up to 26 °C), and the effects of thermal preconditioning as pre-adaptation. Non-adapted stressed hump-snout whitefish showed a higher induction threshold for functionally active mitochondria in the blood and a decrease in telomerase activity in the liver after heat shock exposure as a long-term compensatory response to prevent telomere shortening. However, we observed heat-induced telomere shortening in non-adapted hybrids, which can be explained by a decrease in mitochondrial membrane stability and a gradual increase in energy demand, leading to a decrease in protective telomerase activity. The pre-adapted groups of hump-snout whitefish and hybrids showed a long-term or delayed response of telomerase activity to heat shock, which served as a therapeutic mechanism against telomere shortening. We concluded that the telomerase and telomere responses to thermal stress demonstrate plasticity of tolerance limits and greater stability in hump-snout whitefish compared with hybrids.
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Affiliation(s)
- Yulia P. Sapozhnikova
- Limnological Institute Siberian Branch of the Russian Academy of Sciences, 3 Ulan-Batorskaya, 664033 Irkutsk, Russia; (V.M.Y.); (A.A.V.); (T.N.A.); (O.Y.G.); (M.V.S.); (L.I.T.); (L.V.S.)
| | - Anastasia G. Koroleva
- Limnological Institute Siberian Branch of the Russian Academy of Sciences, 3 Ulan-Batorskaya, 664033 Irkutsk, Russia; (V.M.Y.); (A.A.V.); (T.N.A.); (O.Y.G.); (M.V.S.); (L.I.T.); (L.V.S.)
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