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Jiménez-Rubio G, Herrera-Pérez JJ, Martínez-Mota L. Effect of androgen receptor blockade on spatial memory in young and aged male rats in the Barnes maze. Horm Behav 2025; 170:105711. [PMID: 40058147 DOI: 10.1016/j.yhbeh.2025.105711] [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: 08/16/2024] [Revised: 02/24/2025] [Accepted: 02/27/2025] [Indexed: 04/05/2025]
Abstract
Spatial memory declines with age, and this decline is associated with decreased testosterone levels. However, the specific role of the androgen receptor in spatial memory performance in both young and aged rats remains largely unexplored. Our study aimed to investigate the effects of chronic androgen receptor blockade on spatial memory performance in young and aged male rats. Young (3 months old) and aged (21 months old) Wistar rats were assigned to one of three experimental groups: control, vehicle-, or flutamide-treated (10 mg/kg SC for 14 days). Spatial memory was evaluated using the Barnes maze (Days 8-14 of flutamide administration). The phases of spatial memory acquisition (4 daily trials/4 days) and retention (1 trial/day, 3 days after acquisition) were evaluated. The results indicated that older animals took longer to find the goal, traveled greater distances, and moved more slowly than their younger counterparts in the Barnes maze, regardless of treatment. During the acquisition phase, flutamide administration delayed learning in both young and aged animals. Specifically, flutamide-treated animals exhibited delayed learning during the assessment of overnight forgetting (trial 1 on each day of the acquisition phase). During the retention phase, an age-related effect was observed in the flutamide-treated groups. These findings suggest that androgen receptor blockade induces cognitive deficits in both young and aged male rats, supporting the modulatory role of endogenous androgens in memory function.
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Affiliation(s)
- Graciela Jiménez-Rubio
- Laboratorio de Neurofisiología del Control y la Regulación, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Delegación Tlalpan, 14370 Ciudad de México, Mexico.
| | - José Jaime Herrera-Pérez
- Laboratorio de Farmacología Conductual, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Delegación Tlalpan, 14370 Ciudad de México, Mexico
| | - Lucía Martínez-Mota
- Laboratorio de Farmacología Conductual, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Delegación Tlalpan, 14370 Ciudad de México, Mexico
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Chen MJ, Chen CL, Chang YY, Huang CC, Wu WC, Ho HN, Tseng WYI. Influence of dehydroepiandrosterone sulphate levels on the slower age-related decline in grey matter in younger women with polycystic ovary syndrome. Brain Commun 2025; 7:fcaf052. [PMID: 39958263 PMCID: PMC11829216 DOI: 10.1093/braincomms/fcaf052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 12/22/2024] [Accepted: 02/04/2025] [Indexed: 02/18/2025] Open
Abstract
Polycystic ovary syndrome (PCOS) is characterized by excess androgens, ovulatory disorders and a higher prevalence of obesity and metabolic disturbances including Type 2 diabetes, hyperlipidaemia and hypertension, some of which are risk factors for neurodegenerative disorders such as Alzheimer's disease and brain atrophy. However, it is unclear whether brain ageing occurs more rapidly in women with PCOS compared with those without PCOS. Except for the hypothalamic-pituitary-gonadal axis involved in the conventional ovulatory process, little is known regarding the role of the grey matter in the pathogenesis of PCOS, and limited existing studies examining brain structures in PCOS have shown inconsistent results. This case-control study aimed to investigate the age-related differences in total and regional brain grey matter volume and average cortical thickness in young women with and without PCOS by using brain magnetic resonance imaging to understand whether women with PCOS exhibit distinctive patterns of brain ageing, and their association with factors including obesity, hyperandrogenism and metabolic disturbances. Seventy-six women diagnosed with PCOS and 68 age-matched women without PCOS (aged 20-35 years) underwent brain magnetic resonance imaging to measure grey matter volume and cortical thickness. Anthropometric, hormonal and metabolic measurements were conducted to assess their associations with the investigated brain structures. In women without PCOS, increasing age was significantly correlated with a decrease in global grey matter volume (r = -0.5598, P < 0.0001), while this association was not significant in women with PCOS (r = -0.1475, P = 0.204). The decline in grey matter volume with age differed significantly between the two groups regardless of obesity (body mass index exceeding 25 kg/m2), especially in the frontal, parietal, occipital and temporal regions. After adjusting for dehydroepiandrosterone sulphate (DHEAS) levels, the negative association between age and global grey matter volume became statistically significant in women with PCOS. Increasing age was also significantly associated with a decrease in global cortical thickness in women without PCOS, but not in women with PCOS. Such negative association between global cortical thickness and age was particularly stronger in women with obesity compared with those without. The negative association between age and global cortical thickness in women with PCOS became pronounced after adjusting for DHEAS levels. Women with PCOS experience a milder grey matter loss with age compared with women without PCOS. The neuroprotective effect of high DHEAS levels in women with PCOS may be implicated in this relationship.
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Affiliation(s)
- Mei-Jou Chen
- Department of Obstetrics & Gynecology, National Taiwan University Hospital, Taipei 100, Taiwan
- Livia Shang Yu Wan Chair Professor of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - Chang-Le Chen
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Yu-Yuan Chang
- Department of Obstetrics & Gynecology, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Chu-Chun Huang
- Department of Obstetrics & Gynecology, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Wen-Chau Wu
- Institute of Medical Device and Imaging, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - Hong-Nerng Ho
- Department of Obstetrics & Gynecology, National Taiwan University Hospital, Taipei 100, Taiwan
- Research Center for Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei 100, Taiwan
| | - Wen-Yih Isaac Tseng
- Institute of Medical Device and Imaging, College of Medicine, National Taiwan University, Taipei 100, Taiwan
- AcroViz Inc., Taipei 104, Taiwan
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Haddad R, Bogdanski E, Mattei A, Michel J, Giovanni A. Presbyphonia: A Scoping Review for a Comprehensive Assessment of Aging Voice. J Voice 2024:S0892-1997(24)00432-6. [PMID: 39709303 DOI: 10.1016/j.jvoice.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 11/01/2024] [Accepted: 12/02/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND Presbylarynx refers to age-related changes in the larynx that can manifest clinically as presbyphonia. Several underlying mechanisms remain unclear. OBJECTIVES Perform a scoping review of the published literature on the mechanisms of presbyphonia in order to provide an adequate, comprehensive assessment of aging voice. METHODS AND RESULTS A scoping review on Medline, Cochrane, and Scopus included 188 published articles. Laryngeal aging results in calcifications of the hyaline cartilages, decreased vocal folds lubrication, decreased neuromotor transmission, decreased hyaluronic acid, increased lamina propria stiffness, and changes in the thyroarytenoid muscles. Concomitant aging of the respiratory system, collateral effects of age-related hormonal changes, concomitant presbycusis, and medical comorbidities interact with the presbylarynx to induce clinically detectable voice aging changes (a weak, breathy, or hoarse voice). Based on the results of our study, we proposed a comprehensive assessment of the aging voice, including all the factors involved. CONCLUSION This scoping review proposes a comprehensive assessment of presbyphonia based on the available data. We believe that this assessment will allow a more personalized approach to treatment.
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Affiliation(s)
- Ralph Haddad
- Department of Oto-Rhino-Laryngology and Head and Neck Surgery, AP-HM, La Conception University Hospital, Aix-Marseille University, 147 Boulevard Baille, 13385 Marseille, France.
| | - Estelle Bogdanski
- Department of Oto-Rhino-Laryngology and Head and Neck Surgery, AP-HM, La Conception University Hospital, Aix-Marseille University, 147 Boulevard Baille, 13385 Marseille, France
| | - Alexia Mattei
- Department of Oto-Rhino-Laryngology and Head and Neck Surgery, AP-HM, La Conception University Hospital, Aix-Marseille University, 147 Boulevard Baille, 13385 Marseille, France
| | - Justin Michel
- Department of Oto-Rhino-Laryngology and Head and Neck Surgery, AP-HM, La Conception University Hospital, Aix-Marseille University, 147 Boulevard Baille, 13385 Marseille, France
| | - Antoine Giovanni
- Department of Oto-Rhino-Laryngology and Head and Neck Surgery, AP-HM, La Conception University Hospital, Aix-Marseille University, 147 Boulevard Baille, 13385 Marseille, France
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Conforto R, Rizzo V, Russo R, Mazza E, Maurotti S, Pujia C, Succurro E, Arturi F, Ferro Y, Sciacqua A, Pujia A, Montalcini T. Advances in body composition and gender differences in susceptibility to frailty syndrome: Role of osteosarcopenic obesity. Metabolism 2024; 161:156052. [PMID: 39490438 DOI: 10.1016/j.metabol.2024.156052] [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: 08/05/2024] [Revised: 10/16/2024] [Accepted: 10/23/2024] [Indexed: 11/05/2024]
Abstract
There is general consensus that an improper diet negatively impacts health and that nutrition is a primary tool for the prevention of non-communicable diseases. Unfortunately, the importance of studying body composition, which can reveal early predictors of gender-related diseases, is still not well understood in this context. Currently, individuals are still classified as obese based solely on their body mass index, without considering the amount of fat, its distribution, and the quantity of muscle and bone mass. In this regard, the body composition phenotype defined as "osteosarcopenic obesity" affects approximately 6-41 % of postmenopausal women, with prevalence increasing with age due to the hormonal and metabolic changes that occur during this period. This particular phenotype arises from the strong relationship between visceral fat, muscle, bone, and gut microbiota and predispose postmenopausal women to frailty. Frailty is a complex clinical phenomenon with significant care and economic implications for our society. Recent studies suggest that women have a higher prevalence of frailty syndrome and its individual components, such as osteoporosis, fractures and sarcopenia, compared to men. Here, we provide a comprehensive overview of recent advances regarding the impact of gender on body composition and frailty. Furthermore, we reflect on the crucial importance of personalized nutritional interventions, with a focus on reducing visceral fat, increasing protein intake and optimizing vitamin D levels. A review of the scientific literature on this topic highlights the importance of studying body composition for a personalized and gender-specific approach to nutrition and dietetics, in order to identify frailty syndrome early and establish personalized treatments. This new method of researching disease predictors could likely help clarify the controversial results of studies on vitamin D, calcium and proteins, translate into practical wellness promotion across diverse elderly populations.
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Affiliation(s)
- Rosy Conforto
- Department of Clinical and Experimental Medicine, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy
| | - Valeria Rizzo
- Department of Clinical and Experimental Medicine, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy
| | - Raffaella Russo
- Department of Clinical and Experimental Medicine, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy
| | - Elisa Mazza
- Department of Clinical and Experimental Medicine, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy
| | - Samantha Maurotti
- Department of Clinical and Experimental Medicine, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy.
| | - Carmelo Pujia
- O.U. Clinical Nutrition, Renato Dulbecco Hospital, 88100 Catanzaro, Italy
| | - Elena Succurro
- Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy
| | - Franco Arturi
- Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy
| | - Yvelise Ferro
- Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy
| | - Arturo Pujia
- Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy; Research Center for the Prevention and Treatment of Metabolic Diseases, University "Magna Græcia", 88100 Catanzaro, Italy
| | - Tiziana Montalcini
- Department of Clinical and Experimental Medicine, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy; Research Center for the Prevention and Treatment of Metabolic Diseases, University "Magna Græcia", 88100 Catanzaro, Italy
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Takahashi K, Kitaoka Y, Hatta H. Better maintenance of enzymatic capacity and higher levels of substrate transporter proteins in skeletal muscle of aging female mice. Appl Physiol Nutr Metab 2024; 49:1100-1114. [PMID: 38710106 DOI: 10.1139/apnm-2024-0016] [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: 05/08/2024]
Abstract
This study investigated sex-specific differences in high-energy phosphate, glycolytic, and mitochondrial enzyme activities and also metabolite transporter protein levels in the skeletal muscles of adult (5 months old), middle-aged (12 months old), and advanced-aged (24 months old) mice. While gastrocnemius glycogen content increased with age regardless of sex, gastrocnemius triglyceride levels increased only in advanced-aged female mice. Aging decreased creatine kinase and adenylate kinase activities in the plantaris muscle of both sexes and in the soleus muscle of male mice but not in female mice. Irrespective of sex, phosphofructokinase and lactate dehydrogenase (LDH) activities decreased in the plantaris and soleus muscles. Additionally, hexokinase activity in the plantaris muscle and LDH activity in the soleus muscle decreased to a greater extent in aged male mice compared with those in aged female mice. Mitochondrial enzyme activities increased in the plantaris muscle of aged female mice but did not change in male mice. The protein content of the glucose transporter 4 in the aged plantaris muscle and fatty acid translocase/cluster of differentiation 36 increased in the aged plantaris and soleus muscles of both sexes, with a significantly higher content in female mice. These findings suggest that females possess a better ability to maintain metabolic enzyme activity and higher levels of metabolite transport proteins in skeletal muscle during aging, despite alterations in lipid metabolism. Our data provide a basis for studying muscle metabolism in the context of age-dependent metabolic perturbations and diseases that affect females and males differently.
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Affiliation(s)
- Kenya Takahashi
- Department of Sports Sciences, The University of Tokyo, 3-8-1, Komaba, Meguro-ku, Tokyo 153-8902, Japan
| | - Yu Kitaoka
- Department of Human Sciences, Kanagawa University, 3-27-1, Rokkakubashi, Kanagawa-ku, Yokohama, Kanagawa 221-8686, Japan
| | - Hideo Hatta
- Department of Sports Sciences, The University of Tokyo, 3-8-1, Komaba, Meguro-ku, Tokyo 153-8902, Japan
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Rendon CJ, Sempere L, Lauver A, Watts SW, Contreras GA. Anatomical location, sex, and age modulate adipocyte progenitor populations in perivascular adipose tissues. Front Physiol 2024; 15:1411218. [PMID: 39072214 PMCID: PMC11282503 DOI: 10.3389/fphys.2024.1411218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 06/20/2024] [Indexed: 07/30/2024] Open
Abstract
Perivascular adipose tissue (PVAT) regulates vascular function due to its capacity to synthesize vasoactive products and its mechanical properties. PVATs most abundant cells are adipocytes, and their populations are maintained by the maturation of adipocyte progenitor cells (APC), which may play a pivotal role in the pathogenesis of cardiovascular diseases. However, the distribution of APC within PVAT depots, their potential variation in spatial location, and the influence of sex and age on their abundance remain unknown. We hypothesize that APC abundance in PVAT is affected by location, age, sex and that APC subtypes have specific spatial distributions. PVAT from thoracic and abdominal aorta, and mesenteric arteries, and AT from interscapular, gonadal, and subcutaneous depots from 13-week and 30-week-old females and males Pdgfrα-CreERT2 x LSL-tdTomato mice (n = 28) were analyzed. Abdominal aorta PVAT had fewer progenitors than mesenteric PVAT and gonadal AT. Aging reduced the abundance of APC in the thoracic aorta but increased their numbers in mesenteric PVAT. Females had more APC than males in mesenteric PVAT and gonadal AT depots. APC exhibited unique spatial distribution in the aorta and mesenteric PVAT where they localized neighboring vasa vasorum and arteries. APC subtypes (APC1, APC2, APC3, diff APC) were identified in all PVAT depots. Thoracic aorta PVAT APC3 were located in the adventitia while diff APC were in the parenchyma. This study identified variability in APC populations based on depot, age, and sex. The distinctive spatial distribution and the presence of diverse APC subtypes suggest that they may contribute differently to cardiovascular diseases-induced PVAT remodeling.
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Affiliation(s)
- C. Javier Rendon
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States
| | - Lorenzo Sempere
- Department of Radiology and Precision Health Program, Michigan State University, East Lansing, MI, United States
| | - Adam Lauver
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
| | - Stephanie W. Watts
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States
| | - G. Andres Contreras
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States
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Klinaki E, Ogrodnik M. In the land of not-unhappiness: On the state-of-the-art of targeting aging and age-related diseases by biomedical research. Mech Ageing Dev 2024; 219:111929. [PMID: 38561164 DOI: 10.1016/j.mad.2024.111929] [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: 12/26/2023] [Revised: 03/12/2024] [Accepted: 03/23/2024] [Indexed: 04/04/2024]
Abstract
The concept of the Land of Not-Unhappiness refers to the potential achievement of eliminating the pathologies of the aging process. To inform of how close we are to settling in the land, we summarize and review the achievements of research on anti-aging interventions over the last hundred years with a specific focus on strategies that slow down metabolism, compensate for aging-related losses, and target a broad range of age-related diseases. We critically evaluate the existing interventions labeled as "anti-aging," such as calorie restriction, exercise, stem cell administration, and senolytics, to provide a down-to-earth evaluation of their current applicability in counteracting aging. Throughout the text, we have maintained a light tone to make it accessible to non-experts in biogerontology, and provide a broad overview for those considering conducting studies, research, or seeking to understand the scientific basis of anti-aging medicine.
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Affiliation(s)
- Eirini Klinaki
- Ludwig Boltzmann Research Group Senescence and Healing of Wounds, Vienna 1200, Austria; Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Vienna 1200, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Mikolaj Ogrodnik
- Ludwig Boltzmann Research Group Senescence and Healing of Wounds, Vienna 1200, Austria; Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Vienna 1200, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria.
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Kilpiö T, Skarp S, Perjés Á, Swan J, Kaikkonen L, Saarimäki S, Szokodi I, Penninger JM, Szabó Z, Magga J, Kerkelä R. Apelin regulates skeletal muscle adaptation to exercise in a high-intensity interval training model. Am J Physiol Cell Physiol 2024; 326:C1437-C1450. [PMID: 38525542 DOI: 10.1152/ajpcell.00427.2023] [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: 09/05/2023] [Revised: 03/18/2024] [Accepted: 03/18/2024] [Indexed: 03/26/2024]
Abstract
Plasma apelin levels are reduced in aging and muscle wasting conditions. We aimed to investigate the significance of apelin signaling in cardiac and skeletal muscle responses to physiological stress. Apelin knockout (KO) and wild-type (WT) mice were subjected to high-intensity interval training (HIIT) by treadmill running. The effects of apelin on energy metabolism were studied in primary mouse skeletal muscle myotubes and cardiomyocytes. Apelin increased mitochondrial ATP production and mitochondrial coupling efficiency in myotubes and promoted the expression of mitochondrial genes both in primary myotubes and cardiomyocytes. HIIT induced mild concentric cardiac hypertrophy in WT mice, whereas eccentric growth was observed in the left ventricles of apelin KO mice. HIIT did not affect myofiber size in skeletal muscles of WT mice but decreased the myofiber size in apelin KO mice. The decrease in myofiber size resulted from a fiber type switch toward smaller slow-twitch type I fibers. The increased proportion of slow-twitch type I fibers in apelin KO mice was associated with upregulation of myosin heavy chain slow isoform expression, accompanied with upregulated expression of genes related to fatty acid transport and downregulated expression of genes related to glucose metabolism. Mechanistically, skeletal muscles of apelin KO mice showed defective induction of insulin-like growth factor-1 signaling in response to HIIT. In conclusion, apelin is required for proper skeletal and cardiac muscle adaptation to high-intensity exercise. Promoting apelinergic signaling may have benefits in aging- or disease-related muscle wasting conditions.NEW & NOTEWORTHY Apelin levels decline with age. This study demonstrates that in trained mice, apelin deficiency results in a switch from fast type II myofibers to slow oxidative type I myofibers. This is associated with a concomitant change in gene expression profile toward fatty acid utilization, indicating an aged-muscle phenotype in exercised apelin-deficient mice. These data are of importance in the design of exercise programs for aging individuals and could offer therapeutic target to maintain muscle mass.
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Affiliation(s)
- Teemu Kilpiö
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Sini Skarp
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Ábel Perjés
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Julia Swan
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Leena Kaikkonen
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Samu Saarimäki
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - István Szokodi
- Heart Institute, Medical School, and Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Josef M Penninger
- IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria
- Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - Zoltán Szabó
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
| | - Johanna Magga
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
- Biocenter Oulu, University of Oulu, Oulu, Finland
| | - Risto Kerkelä
- Research Unit of Biomedicine and Internal Medicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
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Rivasi G, Coscarelli A, Capacci M, Ceolin L, Turrin G, Tortù V, D'Andria MF, Testa GD, Ungar A. Tolerability of Antihypertensive Medications: The Influence of Age. High Blood Press Cardiovasc Prev 2024; 31:261-269. [PMID: 38658522 PMCID: PMC11161422 DOI: 10.1007/s40292-024-00639-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: 02/19/2024] [Accepted: 04/02/2024] [Indexed: 04/26/2024] Open
Abstract
INTRODUCTION Despite high prevalence of hypertension, few studies have analysed the adverse effects (AEs) of antihypertensive medications, especially in older patients. AIM To investigate the prevalence and associated factors of antihypertensive-related AEs, focusing on the influence of age on treatment tolerability. METHODS We retrospectively investigated antihypertensive-related AEs in patients evaluated at the Hypertension Clinic of Careggi Hospital, Florence, Italy, between January 2017 and July 2020. Multivariable regression models were generated to analyse variables associated with AEs in the overall sample and in participants ≥75 years. RESULTS Among 622 subjects (mean age 64.8 years, 51.4% female), the most frequently reported AEs were calcium-channel blockers (CCB)-related ankle swelling (26.8%) and ACEi-induced cough (15.1%). Ankle swelling was more common in older patients (35.7% vs 22.3%, p = 0.001; odds ratio [OR] 1.94, 95%CI 1.289-2.912) and was independently associated with Body Mass Index (BMI, adjOR 1.073) and angiotensin-receptor antagonists (adjOR 1.864). The association with BMI was confirmed in older patients (adjOR 1.134). ACEi-induced cough showed similar prevalence in younger and older patients (13.9% vs 15.6%, p = 0.634), being independently associated with female sex (adjOR 2.118), gastroesophageal reflux disease (GERD, adjOR 2.488) and SNRI therapy (adjOR 8.114). The association with GERD was confirmed in older patients (adjOR 3.238). CONCLUSIONS CCB-related ankle swelling and ACEi-induced cough represent the most common antihypertensive-related AEs, also at old age. Older patients showed a two-fold increased risk of ankle swelling, that was also independently associated with BMI. ACEi-induced cough had similar prevalence at younger and old ages, being independently associated with GERD.
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Affiliation(s)
- Giulia Rivasi
- Division of Geriatric and Intensive Care Medicine, Referral Centre for Hypertension in Older Adults, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy.
| | - Antonio Coscarelli
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Marco Capacci
- Division of Geriatric and Intensive Care Medicine, Referral Centre for Hypertension in Older Adults, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Ludovica Ceolin
- Division of Geriatric and Intensive Care Medicine, Referral Centre for Hypertension in Older Adults, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Giada Turrin
- Division of Geriatric and Intensive Care Medicine, Referral Centre for Hypertension in Older Adults, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Virginia Tortù
- Division of Geriatric and Intensive Care Medicine, Referral Centre for Hypertension in Older Adults, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Maria Flora D'Andria
- Division of Geriatric and Intensive Care Medicine, Referral Centre for Hypertension in Older Adults, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Giuseppe Dario Testa
- Division of Geriatric and Intensive Care Medicine, Referral Centre for Hypertension in Older Adults, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
| | - Andrea Ungar
- Division of Geriatric and Intensive Care Medicine, Referral Centre for Hypertension in Older Adults, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Florence, Italy
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Gómez-Redondo P, Valenzuela PL, Martínez-de-Quel Ó, Sánchez-Martín C, Cerezo-Arroyo M, Moreno-Manzanaro D, Alegre LM, Guadalupe-Grau A, Ara I, Mañas A. The role of supervision and motivation during exercise on physical and mental health in older adults: a study protocol for a randomized controlled trial (PRO-Training project). BMC Geriatr 2024; 24:274. [PMID: 38509514 PMCID: PMC10953175 DOI: 10.1186/s12877-024-04868-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 03/04/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND Although supervised exercise is frequently recommended for older adults, its superiority over unsupervised exercise remains uncertain. Furthermore, whether motivational techniques could help to enhance the effectiveness of the latter remains to be elucidated. The present randomized controlled trial aims to determine the role of supervision and motivational strategies on the safety, adherence, efficacy, and cost-effectiveness of different exercise programs for improving physical and mental health in older adults. METHODS Participants (n = 120, aged 60-75 years) will be randomly allocated into five groups: 1-Control (CON), 2-Supervised exercise without motivational intervention (SUP), 3- Supervised exercise with motivational intervention (SUP +), 4- Unsupervised exercise without motivational intervention (UNSUP) and 5- Unsupervised exercise with motivational intervention (UNSUP +). Over 24 weeks, all exercise groups will participate in a multicomponent exercise program three times/week (performed in group classes at a center for SUP and SUP + , or home without supervision but with the help of a mobile app for UNSUP and UNSUP +), while the CON group will maintain their usual lifestyle. The motivational intervention (for SUP + and UNSUP + groups) will be based on the self-determination theory, including strategies such as phone calls, interactive workshops, motivational messages, informative infographics and videos. Primary outcomes will include safety, adherence, costs, and lower-body muscular function using a leg press machine. Secondary outcomes will include upper-body muscular function, physical and cardiorespiratory function, blood pressure and heart rate, body composition, health-related quality of life, cognitive performance, anxiety, depression, physical activity levels, sleep and sedentarism, biochemical markers, motivators and barriers to exercise. Assessments will be conducted at baseline, mid-intervention (i.e., week 13), at the end of the intervention (i.e., week 25), and 24 weeks later (i.e., week 49). DISCUSSION The findings of this trial might provide valuable insights into the role of supervision and motivational strategies on the effectiveness of exercise programs for older adults. Additionally, the study could contribute to developing cost-effective interventions, supporting the design of future public policies for healthy aging. TRIAL REGISTRATION NCT05619250. Registered 16 November 2022.
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Affiliation(s)
- Paola Gómez-Redondo
- GENUD Toledo Research Group, Faculty of Sports Sciences, University of Castilla-La Mancha, Avda. Carlos III S/N, 45071, Toledo, Spain
- CIBER of Frailty and Healthy Aging, Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Junta de Comunidades de Castilla-La Mancha (JCCM), Toledo, Spain
| | - Pedro L Valenzuela
- Physical Activity and Health Research Group (PaHerg), Research Institute of Hospital, 12 de Octubre (imas12), Madrid, Spain
- Department of Systems Biology, University of Alcalá, Madrid, Spain
| | - Óscar Martínez-de-Quel
- Didactics of Languages, Arts and Physical Education Department, Faculty of Education, Complutense University of Madrid, 28040, Madrid, Spain
- Faculty of Sciences for Physical Activity and Sport (INEF), Polytechnic University of Madrid, 28040, Madrid, Spain
| | - Coral Sánchez-Martín
- GENUD Toledo Research Group, Faculty of Sports Sciences, University of Castilla-La Mancha, Avda. Carlos III S/N, 45071, Toledo, Spain
- CIBER of Frailty and Healthy Aging, Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Junta de Comunidades de Castilla-La Mancha (JCCM), Toledo, Spain
| | - Mónica Cerezo-Arroyo
- GENUD Toledo Research Group, Faculty of Sports Sciences, University of Castilla-La Mancha, Avda. Carlos III S/N, 45071, Toledo, Spain
- CIBER of Frailty and Healthy Aging, Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Junta de Comunidades de Castilla-La Mancha (JCCM), Toledo, Spain
| | - David Moreno-Manzanaro
- GENUD Toledo Research Group, Faculty of Sports Sciences, University of Castilla-La Mancha, Avda. Carlos III S/N, 45071, Toledo, Spain
- CIBER of Frailty and Healthy Aging, Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Junta de Comunidades de Castilla-La Mancha (JCCM), Toledo, Spain
| | - Luis M Alegre
- GENUD Toledo Research Group, Faculty of Sports Sciences, University of Castilla-La Mancha, Avda. Carlos III S/N, 45071, Toledo, Spain
- CIBER of Frailty and Healthy Aging, Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Junta de Comunidades de Castilla-La Mancha (JCCM), Toledo, Spain
| | - Amelia Guadalupe-Grau
- GENUD Toledo Research Group, Faculty of Sports Sciences, University of Castilla-La Mancha, Avda. Carlos III S/N, 45071, Toledo, Spain
- CIBER of Frailty and Healthy Aging, Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Junta de Comunidades de Castilla-La Mancha (JCCM), Toledo, Spain
| | - Ignacio Ara
- GENUD Toledo Research Group, Faculty of Sports Sciences, University of Castilla-La Mancha, Avda. Carlos III S/N, 45071, Toledo, Spain
- CIBER of Frailty and Healthy Aging, Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Junta de Comunidades de Castilla-La Mancha (JCCM), Toledo, Spain
| | - Asier Mañas
- GENUD Toledo Research Group, Faculty of Sports Sciences, University of Castilla-La Mancha, Avda. Carlos III S/N, 45071, Toledo, Spain.
- CIBER of Frailty and Healthy Aging, Instituto de Salud Carlos III, Madrid, Spain.
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Junta de Comunidades de Castilla-La Mancha (JCCM), Toledo, Spain.
- Didactics of Languages, Arts and Physical Education Department, Faculty of Education, Complutense University of Madrid, 28040, Madrid, Spain.
- Center UCM-ISCIII for Human Evolution and Behavior, 28029, Madrid, Spain.
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11
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Chen Z, Zhang E, Gan L, Jiang G, Duan Q, Huang M, Li H, Huang G. Analysis of the association between testosterone and cardiovascular disease potential risk factor apolipoprotein B in adult males without cancer: national health and nutrition examination survey 2011-2016. Front Endocrinol (Lausanne) 2024; 15:1304344. [PMID: 38435750 PMCID: PMC10905265 DOI: 10.3389/fendo.2024.1304344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 01/22/2024] [Indexed: 03/05/2024] Open
Abstract
Background Over the years, there has been extensive exploration of the association between testosterone and lipid profiles, yet the precise mechanisms underlying their interaction remain incompletely elucidated. Similarly, there is a dearth of research on the correlation between serum apolipoprotein B (apoB) and serum total testosterone (TT), particularly within specific populations. Methods We conducted a cross-sectional study to assess the relationship between serum TT concentration and serum apoB concentration. Using the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016, we employed weighted generalized linear models, weighted univariate, weighted multivariate analysis, and smooth curve fitting to assist in exploring the relationship between serum TT and apoB. Serum apoB concentration served as the independent variable, and serum TT concentration as the dependent variable. ApoB was divided into four quartiles-Q1 (<0.7g/L, N=691), Q2 (≥0.7g/L to <0.9g/L, N=710), Q3 (≥0.9g/L to <1.1g/L, N=696), and Q4 (≥1.1g/L, N=708)-thereby further solidifying the stable association between the two. Additionally, the application of smooth curve fitting will contribute to a more detailed elucidation of the specific relationship between serum TT concentration and serum apoB concentration under different factors (Drinking, Smoke, Diabetes, Hypertension, and High cholesterol level.). Results The results indicate a negative correlation between serum TT concentration and apoB concentration (β=-113.4; 95% CI: -146.6, -80.2; P<0.001). After adjusting for confounding variables, the negative correlation between apoB concentration and TT concentration remains significant (β=-61.0; 95% CI: -116.7, -5.2; P=0.040). When apoB concentration was converted from a continuous variable to a categorical variable (quartiles: Q1<0.7g/L; Q2:≥0.7g/L to<0.9g/L; Q3:≥0.9g/L to <1.1g/L; Q4: ≥1.1g/L), TT level of participants in the highest quartile (≥1.1g/L) was -47.2 pg/mL (95% CI: -91.2, -3.3; P=0.045) lower than that in the lowest quartile (<0.7g/L). The smooth curve fitting diagram revealed differences in the relationship between TT concentration and apoB among individuals with different cardiovascular disease (CVD) risk factors. Conclusions This study elucidates a robust inverse correlation between serum TT concentration and apoB concentration, maintaining statistical significance even upon adjustment for confounding factors. These findings present a promising avenue for addressing the prevention and treatment of low testosterone and CVD.
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Affiliation(s)
- Zhiyi Chen
- Department of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China
- Department of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen, China
| | - Enpu Zhang
- Department of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen, China
| | - Lu Gan
- Department of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen, China
| | - Ganggang Jiang
- Department of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen, China
| | - Qilin Duan
- Department of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen, China
| | - Mou Huang
- Department of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen, China
| | - Huizhen Li
- Department of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen, China
| | - Guixiao Huang
- Department of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China
- Department of Urology, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen, China
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12
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Shi J, Wang X, Qi W, Wang S, Fu Y, Zhang Y, Zhang Q, Han L, Xu Y, Duan H, Liu J, Cong X, Zhou C, Zhao P, Wang J. Association between NTCP hepatic expression and inflammation/fibrosis as well as gender-specific differences in chronic HBV-infected patients. J Med Virol 2024; 96:e29428. [PMID: 38258306 DOI: 10.1002/jmv.29428] [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: 07/24/2023] [Revised: 01/09/2024] [Accepted: 01/14/2024] [Indexed: 01/24/2024]
Abstract
To investigate the relationship between the expression of hepatitis B virus (HBV) functional receptor sodium taurocholate cotransporting polypeptide (NTCP) with disease progression and gender-specific differences in chronic HBV-infected patients. Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery. HBV DNA levels and the mRNA and protein expression levels of NTCP in liver tissues were determined. The relationship between NTCP expression and HBV DNA levels, inflammatory activity, fibrosis, and gender-specific differences were analyzed. A total of 94 chronic HBV-infected patients were included. Compared with patients with a METAVIR score of A0-1 or F0-1, patients with score of A2 or F2/F3 had a relatively higher level of NTCP expression. NTCP levels were positively correlated with HBV DNA levels. The inflammatory activity scores and fibrosis scores of women <50 years were significantly lower than those of women ≥50 years and age-matched males. In patients with score A0-2 or F0-3, women <50 years have lower NTCP expression level compared to women ≥50 years and age-matched males. NTCP can promote the disease progression by affecting the viral load of HBV. The NTCP expression difference may be why male and postmenopausal women are more prone to disease progression than reproductive women.
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Affiliation(s)
- Jingyi Shi
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xu Wang
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Wenqian Qi
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Song Wang
- Department of Urology, The First Hospital of Jilin University, Changchun, China
| | - Yao Fu
- Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, China
| | - Yonggui Zhang
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Qian Zhang
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Liang Han
- Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Yanhui Xu
- Department of Gastroenterology and Hepatology, People's Hospital of Zhengzhou University and Henan Provincial People's Hospital, Zhengzhou, China
| | - Honglei Duan
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jia Liu
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xianling Cong
- Department of Biobank, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Changyu Zhou
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Ping Zhao
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jiangbin Wang
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, China
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13
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Chen Y, Zhen Z, Chen L, Wang H, Wang X, Sun X, Song Z, Wang H, Lin Y, Zhang W, Wu G, Jiang Y, Mao Z. Androgen signaling stabilizes genomes to counteract senescence by promoting XRCC4 transcription. EMBO Rep 2023; 24:e56984. [PMID: 37955230 PMCID: PMC10702805 DOI: 10.15252/embr.202356984] [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: 02/13/2023] [Revised: 10/16/2023] [Accepted: 10/24/2023] [Indexed: 11/14/2023] Open
Abstract
Aging is accompanied by a decreased DNA repair capacity, which might contribute to age-associated functional decline in multiple tissues. Disruption in hormone signaling, associated with reproductive organ dysfunction, is an early event of age-related tissue degeneration, but whether it impacts DNA repair in nonreproductive organs remains elusive. Using skin fibroblasts derived from healthy donors with a broad age range, we show here that the downregulation of expression of XRCC4, a factor involved in nonhomologous end-joining (NHEJ) repair, which is the dominant pathway to repair somatic double-strand breaks, is mediated through transcriptional mechanisms. We show that the androgen receptor (AR), whose expression is also reduced during aging, directly binds to and enhances the activity of the XRCC4 promoter, facilitating XRCC4 transcription and thus stabilizing the genome. We also demonstrate that dihydrotestosterone (DHT), a powerful AR agonist, restores XRCC4 expression and stabilizes the genome in different models of cellular aging. Moreover, DHT treatment reverses senescence-associated phenotypes, opening a potential avenue to aging interventions in the future.
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Affiliation(s)
- Yu Chen
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Zhengyi Zhen
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Lingjiang Chen
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Hao Wang
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Xuhui Wang
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Xiaoxiang Sun
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Zhiwei Song
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Haiyan Wang
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Yizi Lin
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Wenjun Zhang
- Department of Plastic Surgery, Changzheng Hospital, Shanghai, China
| | - Guizhu Wu
- Department of Gynecology, Shanghai First Maternity and Infant Hospital, Shanghai Tongji University School of Medicine, Shanghai, China
| | - Ying Jiang
- Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Zhiyong Mao
- Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
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14
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Pataky MW, Dasari S, Michie KL, Sevits KJ, Kumar AA, Klaus KA, Heppelmann CJ, Robinson MM, Carter RE, Lanza IR, Nair KS. Impact of biological sex and sex hormones on molecular signatures of skeletal muscle at rest and in response to distinct exercise training modes. Cell Metab 2023; 35:1996-2010.e6. [PMID: 37939659 PMCID: PMC10659143 DOI: 10.1016/j.cmet.2023.10.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 05/09/2023] [Accepted: 10/13/2023] [Indexed: 11/10/2023]
Abstract
Substantial divergence in cardio-metabolic risk, muscle size, and performance exists between men and women. Considering the pivotal role of skeletal muscle in human physiology, we investigated and found, based on RNA sequencing (RNA-seq), that differences in the muscle transcriptome between men and women are largely related to testosterone and estradiol and much less related to genes located on the Y chromosome. We demonstrate inherent unique, sex-dependent differences in muscle transcriptional responses to aerobic, resistance, and combined exercise training in young and older cohorts. The hormonal changes with age likely explain age-related differential expression of transcripts. Furthermore, in primary human myotubes we demonstrate the profound but distinct effects of testosterone and estradiol on amino acid incorporation to multiple individual proteins with specific functions. These results clearly highlight the potential of designing exercise programs tailored specifically to men and women and have implications for people who change gender by altering their hormone profile.
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Affiliation(s)
- Mark W Pataky
- Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA
| | - Surendra Dasari
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Kelly L Michie
- Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA
| | - Kyle J Sevits
- Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA
| | - A Aneesh Kumar
- Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA
| | - Katherine A Klaus
- Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA
| | | | - Matthew M Robinson
- School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA
| | - Rickey E Carter
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Ian R Lanza
- Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA
| | - K Sreekumaran Nair
- Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, USA.
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15
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Yasui S, Kaneko Y, Yamagami H, Hosoki M, Hori T, Tani A, Hara T, Kurahashi K, Harada T, Nakamura S, Otoda T, Yuasa T, Mori H, Kuroda A, Endo I, Matsuhisa M, Soeki T, Aihara KI. Dehydroepiandrosterone Sulfate, an Adrenal Androgen, Is Inversely Associated with Prevalence of Dynapenia in Male Individuals with Type 2 Diabetes. Metabolites 2023; 13:1129. [PMID: 37999225 PMCID: PMC10673440 DOI: 10.3390/metabo13111129] [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: 08/31/2023] [Revised: 10/13/2023] [Accepted: 11/01/2023] [Indexed: 11/25/2023] Open
Abstract
Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. Although skeletal muscle disorders are often found in diabetic people, the clinical significance of DHEAS in skeletal muscle remains unclear. Therefore, we aimed to determine whether DHEAS is associated with the development of skeletal muscle disorders in individuals with type 2 diabetes (T2D). A cross-sectional study was conducted in 361 individuals with T2D. Serum DHEAS levels, skeletal muscle mass index (SMI), handgrip strength (HS), and gait speed (GS) were measured in the participants. Pre-sarcopenia, sarcopenia, and dynapenia were defined according to the definitions of the AWGS 2019 criteria. DHEAS level was positively associated with HS but not with SMI or GS after adjustment of confounding factors. Multiple logistic regression analyses in total subjects showed that DHEAS level had an inverse association with the prevalence of dynapenia but not with the prevalence of pre-sarcopenia or sarcopenia. Furthermore, a significant association between DHEAS level and dynapenia was found in males but not in females. ROC curve analysis indicated that cutoff values of serum DHEAS for risk of dynapenia in males was 92.0 μg/dL. Therefore, in male individuals with T2D who have low serum levels of DHEAS, adequate exercise might be needed to prevent dynapenia.
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Affiliation(s)
- Saya Yasui
- Department of Internal Medicine, Anan Medical Center, 6-1 Kawahara Takarada-cho, Anan 774-0045, Japan; (S.Y.); (Y.K.); (H.Y.); (M.H.); (T.H.); (A.T.)
| | - Yousuke Kaneko
- Department of Internal Medicine, Anan Medical Center, 6-1 Kawahara Takarada-cho, Anan 774-0045, Japan; (S.Y.); (Y.K.); (H.Y.); (M.H.); (T.H.); (A.T.)
| | - Hiroki Yamagami
- Department of Internal Medicine, Anan Medical Center, 6-1 Kawahara Takarada-cho, Anan 774-0045, Japan; (S.Y.); (Y.K.); (H.Y.); (M.H.); (T.H.); (A.T.)
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (T.H.); (K.K.); (T.H.)
| | - Minae Hosoki
- Department of Internal Medicine, Anan Medical Center, 6-1 Kawahara Takarada-cho, Anan 774-0045, Japan; (S.Y.); (Y.K.); (H.Y.); (M.H.); (T.H.); (A.T.)
| | - Taiki Hori
- Department of Internal Medicine, Anan Medical Center, 6-1 Kawahara Takarada-cho, Anan 774-0045, Japan; (S.Y.); (Y.K.); (H.Y.); (M.H.); (T.H.); (A.T.)
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (T.H.); (K.K.); (T.H.)
| | - Akihiro Tani
- Department of Internal Medicine, Anan Medical Center, 6-1 Kawahara Takarada-cho, Anan 774-0045, Japan; (S.Y.); (Y.K.); (H.Y.); (M.H.); (T.H.); (A.T.)
| | - Tomoyo Hara
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (T.H.); (K.K.); (T.H.)
| | - Kiyoe Kurahashi
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (T.H.); (K.K.); (T.H.)
| | - Takeshi Harada
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (T.H.); (K.K.); (T.H.)
| | - Shingen Nakamura
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (S.N.); (T.O.); (T.Y.); (T.S.)
| | - Toshiki Otoda
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (S.N.); (T.O.); (T.Y.); (T.S.)
| | - Tomoyuki Yuasa
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (S.N.); (T.O.); (T.Y.); (T.S.)
| | - Hiroyasu Mori
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (H.M.); (A.K.); (M.M.)
| | - Akio Kuroda
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (H.M.); (A.K.); (M.M.)
| | - Itsuro Endo
- Department of Bioregulatory Sciences, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan;
| | - Munehide Matsuhisa
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (H.M.); (A.K.); (M.M.)
| | - Takeshi Soeki
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (S.N.); (T.O.); (T.Y.); (T.S.)
| | - Ken-ichi Aihara
- Department of Internal Medicine, Anan Medical Center, 6-1 Kawahara Takarada-cho, Anan 774-0045, Japan; (S.Y.); (Y.K.); (H.Y.); (M.H.); (T.H.); (A.T.)
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan; (S.N.); (T.O.); (T.Y.); (T.S.)
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Duan H, Wang X, Qi W, Shi J, Han L, Wang G, Xu Y, Liu J, Wang J. Two genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infection. Biol Sex Differ 2023; 14:68. [PMID: 37784175 PMCID: PMC10546680 DOI: 10.1186/s13293-023-00553-4] [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: 07/27/2023] [Accepted: 09/24/2023] [Indexed: 10/04/2023] Open
Abstract
BACKGROUND To examine the expression characteristics of single nucleotide polymorphisms (SNPs) in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus (HBV) infection. METHODS A total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors, namely AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, were genotyped in 1007 patients from eight counties (cities) in Northeastern China with chronic HBV infection and 1040 healthy controls, and their association with viral replication characteristics and the differences in disease severity between sexes was assessed. Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients. RESULTS Two SNP loci in the SRD5A2 gene (rs12470143 and rs7594951) exhibited significant differences in genotype and allele frequencies between sexes, with the proportion of T alleles significantly higher in males than in females. It was found that the incidence and severity of HBV-related liver fibrosis were significantly higher in patients with the T/T genotype in SRD5A2 rs12470143 and rs7594951 than those with the non-T/T genotype. Additionally, serum HBV DNA levels were significantly elevated in T/T patients compared to non-T/T patients. Female patients exhibited significantly lower serum DNA levels compared to male patients. Western blot analysis indicated that greater hepatic SRD5A2 protein levels were associated with higher METAVIR inflammation and fibrosis scores. Furthermore, multivariate analysis showed that the two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T), together with the male sex, age > 50 years old, HBeAg positive status, elevated serum HBsAg load, high serum HBV DNA load, and HBV genotype C, were independent risk factors for HBV-related liver fibrosis. CONCLUSIONS This study demonstrated that two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T) are associated with sex differences in the clinical characteristics of patients with chronic HBV infection.
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Affiliation(s)
- Honglei Duan
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China
| | - Xu Wang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China
| | - Wenqian Qi
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China
| | - Jingyi Shi
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China
| | - Liang Han
- Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China
| | - Guohua Wang
- Department of Gastroenterology and Nephrology, Songyuan Jilin Oilfield Hospital, Songyuan, 138000, Jilin, China
| | - Yanhui Xu
- Department of Gastroenterology and Hepatology, People's Hospital of Zhengzhou University and Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China
| | - Jia Liu
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China
| | - Jiangbin Wang
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., Changchun, 130033, Jilin, China.
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17
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Nonaka K, Takubo K, Aida J, Watai Y, Komatsu A, Gomi F, Shichi Y, Yamazaki Y, Ishiwata T, Sasano H, Arai T. Accelerated telomere shortening in adrenal zona reticularis in patients with prolonged critical illness. Front Endocrinol (Lausanne) 2023; 14:1244553. [PMID: 37745694 PMCID: PMC10512174 DOI: 10.3389/fendo.2023.1244553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 08/18/2023] [Indexed: 09/26/2023] Open
Abstract
Background The number of patients with prolonged critical illness (PCI) has been increasing in many countries, and the adrenal gland plays an important role in maintaining homeostasis during PCI. Chronic disease burden is reportedly associated with shorter telomere lengths in human tissues. Telomere shortening in human somatic cells is largely dependent on cell divisions, and critically short telomeres lead to cellular dysfunction and aging. However, the association between PCI and telomere lengths in human adrenal cells is poorly understood. In this study, we investigated this association to assess whether the burden of PCI could accelerate the aging process in adrenal cells. Methods Adrenocortical tissues from patients who died after PCI usually show a diffuse pattern of intracellular cholesterol ester depletion (i.e., lipid depletion). This study examined near-normal adrenal glands obtained from autopsied patients who died suddenly (control group) and lipid-depleted adrenal glands obtained from autopsied patients who died after PCI (PCI group). The control group included 7 men aged 80 to 94 years (mean age: 85.3 years) and 7 women aged 84 to 94 years (mean age: 87.7 years). The PCI group included 10 men aged 71 to 88 years (mean age: 78.8 years) and 8 women aged 77 to 95 years (mean age: 85.6 years). By using quantitative fluorescence in situ hybridization, relative telomere lengths (RTLs) were determined in the parenchymal cells of the three adrenocortical zones (zona glomerulosa, zona fasciculata, and zona reticularis [ZR]) and in the chromaffin cells of the medulla. The number of adrenal parenchymal cells was determined by immunohistochemistry and digital image analysis. Results RTLs in ZR cells were significantly shorter in the PCI group than in the control group for both men and women (P = 0.0001 for men and P = 0.0012 for women). However, RTLs in the remaining three types of adrenal cells did not differ between the control and PCI groups for both men and women. The number of ZR cells was higher in the PCI group than in the control group for both men and women (P < 0.0001 for both men and women). The proportion of the number of ZR cells to the total number of adrenocortical parenchymal cells was also higher in the PCI group than in the control group (P < 0.0001 for both men and women). The Ki-67 proliferation index in ZR cells was higher in the PCI group than in the control group (P = 0.0039 for men and P = 0.0063 for women). Conclusions This study demonstrated ZR cell-specific telomere shortening in patients with adrenal lipid depletion who died after PCI. Our results suggest that the reactive proliferation of ZR cells accelerates the telomere shortening and aging process in ZR cells in these patients. The results of our study may contribute to the understanding of adrenal aging during PCI.
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Affiliation(s)
- Keisuke Nonaka
- Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
| | - Kaiyo Takubo
- Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
| | - Junko Aida
- Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
| | - Yoriko Watai
- Department of Drug Discovery Support Business, Summit Pharmaceuticals International, Tokyo, Japan
| | - Akiko Komatsu
- Department of Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
| | - Fujiya Gomi
- Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
| | - Yuuki Shichi
- Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
| | - Yuto Yamazaki
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Toshiyuki Ishiwata
- Division of Aging and Carcinogenesis, Research Team for Geriatric Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomio Arai
- Department of Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan
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18
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Kumar M, Orkaby A, Tighe C, Villareal DT, Billingsley H, Nanna MG, Kwak MJ, Rohant N, Patel S, Goyal P, Hummel S, Al-Malouf C, Kolimas A, Krishnaswami A, Rich MW, Kirkpatrick J, Damluji AA, Kuchel GA, Forman DE, Alexander KP. Life's Essential 8: Optimizing Health in Older Adults. JACC. ADVANCES 2023; 2:100560. [PMID: 37664644 PMCID: PMC10470487 DOI: 10.1016/j.jacadv.2023.100560] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 06/26/2023] [Accepted: 07/07/2023] [Indexed: 09/05/2023]
Abstract
The population worldwide is getting older as a result of advances in public health, medicine, and technology. Older individuals are living longer with a higher prevalence of subclinical and clinical cardiovascular disease (CVD). In 2010, the American Heart Association introduced a list of key prevention targets, known as "Life's Simple 7" to increase CVD-free survival, longevity, and quality of life. In 2022, sleep health was added to expand the recommendations to "Life's Essential 8" (eat better, be more active, stop smoking, get adequate sleep, manage weight, manage cholesterol, manage blood pressure, and manage diabetes). These prevention targets are intended to apply regardless of chronologic age. During this same time, the understanding of aging biology and goals of care for older adults further enhanced the relevance of prevention across the range of functions. From a biological perspective, aging is a complex cellular process characterized by genomic instability, telomere attrition, loss of proteostasis, inflammation, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These aging hallmarks are triggered by and enhanced by traditional CVD risk factors leading to geriatric syndromes (eg, frailty, sarcopenia, functional limitation, and cognitive impairment) which complicate efforts toward prevention. Therefore, we review Life's Essential 8 through the lens of aging biology, geroscience, and geriatric precepts to guide clinicians taking care of older adults.
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Affiliation(s)
- Manish Kumar
- Pat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut, USA
- UConn Center on Aging, University of Connecticut School of Medicine, Farmington, Connecticut, USA
| | - Ariela Orkaby
- New England GRECC (Geriatric Research Education and Clinical Center), VA Boston HealthCare System, Boston, Massachusetts, USA
- Division of Aging, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Caitlan Tighe
- VISN 4 Mental Illness Research, Education and Clinical Center, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
| | - Dennis T. Villareal
- Division of Endocrinology, Diabetes, and Metabolism, Baylor College of Medicine, Houston, Texas, USA
| | - Hayley Billingsley
- Division of Cardiovascular Medicine, University of Michigan Frankel Cardiovascular Center, Ann Arbor, Michigan, USA
| | - Michael G. Nanna
- Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Min Ji Kwak
- Division of Geriatric and Palliative Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA
| | - Namit Rohant
- Department of Cardiology, University of Arizona, Tucson, Arizona, USA
| | - Shreya Patel
- Department of Pharmacy Practice, School of Pharmacy and Health Sciences, Fairleigh Dickinson University, Florham Park, New Jersey, USA
| | - Parag Goyal
- Program for the Care and Study of Aging Heart, Department of Medicine, Weill Cornell of Medicine, New York, New York, USA
| | - Scott Hummel
- Division of Cardiovascular Medicine, University of Michigan Frankel Cardiovascular Center, Ann Arbor, Michigan, USA
| | - Christina Al-Malouf
- Department of Cardiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Amie Kolimas
- Department of Internal Medicine, University of Arizona, Tucson, Arizona, USA
| | | | - Michael W. Rich
- Department of Medicine, Washington University, St Louise, Missouri, USA
| | - James Kirkpatrick
- Department of Cardiology, University of Washington, Seattle, Washington, USA
| | - Abdulla A. Damluji
- The Inova Center of Outcomes Research, Inova Heart and Vascular Institute, Falls Church, Virginia, USA
| | - George A. Kuchel
- UConn Center on Aging, University of Connecticut School of Medicine, Farmington, Connecticut, USA
| | - Daniel E. Forman
- Divisions of Cardiology and Geriatrics, Department of Medicine, University of Pittsburgh, Pittsburgh GRECC, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
| | - Karen P. Alexander
- Division of Cardiology, Duke Medicine, Duke Clinical Research Institute, Durham, North Carolina, USA
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Arıcı A, Erdemir F. A Determination of p97/VCP (Valosin Containing Protein) and SVIP (Small VCP Interacting Protein) Expression Patterns in Human Testis. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1079. [PMID: 37374283 DOI: 10.3390/medicina59061079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 05/31/2023] [Accepted: 06/01/2023] [Indexed: 06/29/2023]
Abstract
Background and Objectives: The ubiquitin proteosome system (UPS) is a non-lysosomal pathway that functions in all eukaryotes. The transport of polyubiquitinated proteins to proteosomes takes place via the p97/Valosin-containing protein (VCP) chaperone protein. The p97/VCP binds to polyubiquitinated proteins, allowing these proteins to reach the proteasome and, thus, their destruction. In the case of p97/VCP deficiency, ubiquitinated proteins accumulate in the cell cytoplasm, and their subsequent failure to break down produces various pathological conditions. Small VCP interacting protein (SVIP) and p97/VCP proteins have not been studied in human testicular tissues from different postnatal periods. Therefore, in our study, we aimed to examine the expression of SVIP and p97/VCP in postnatal human testicular tissues. Our study aimed to contribute to further studies on the use of these proteins as testicular cell biomarkers in cases of unexplained male infertility. Materials and Methods: Immunohistochemical studies with the aim of determining the expression of p97/VCP and SVIP proteins in neonatal, prepubertal, pubertal, adult, and geriatric human testis tissues were performed. Results: In testicular sections obtained from a neonatal group, p97/VCP and SVIP were localized in different testicular and interstitial cells, and the lowest expression was observed in this group. While the expressions of these proteins were low in the neonatal period, they increased gradually in the prepubertal, pubertal and adult periods. The expression of p97/VCP and SVIP, which peaked in adulthood, showed a significant decrease in the geriatric period. Conclusions: As a result, the expression of p97/VCP and SVIP correlated with the increase in age, but it decreased significantly in older groups.
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Affiliation(s)
- Akgül Arıcı
- Department of Medical Pathology, Tokat Gaziosmanpasa University, 60100 Tokat, Turkey
| | - Fikret Erdemir
- Department of Urology, Tokat Gaziosmanpasa University, 60100 Tokat, Turkey
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20
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Lim ST, Kang S. Exercise therapy for sarcopenia and diabetes. World J Diabetes 2023; 14:565-572. [PMID: 37273255 PMCID: PMC10237001 DOI: 10.4239/wjd.v14.i5.565] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 02/13/2023] [Accepted: 04/10/2023] [Indexed: 05/15/2023] Open
Abstract
Aging is characterized by the gradual deterioration of function at the molecular, cellular, tissue, and organism levels in humans. The typical diseases caused by changes in body composition, as well as functional decline in the human body’s organs due to aging include sarcopenia and metabolic disorders. The accumulation of dysfunctional aging β cells with age can cause decreased glucose tolerance and diabetes. Muscle decline has a multifactorial origin, involving lifestyle habits, disease triggers, and age-dependent biological changes. The reduced function of β cells in elderly people lowers insulin sensitivity, which affects protein synthesis and interferes with muscle synthesis. The functional decrease and aggravation of disease in elderly people with less regular exercise or physical activity causes imbalances in food intake and a continuous, vicious cycle. In contrast, resistance exercise increases the function of β cells and protein synthesis in elderly people. In this review, we discuss regular physical activities or exercises to prevent and improve health, which is sarcopenia as decreased muscle mass and metabolic disorders as diabetes in the elderly.
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Affiliation(s)
- Seung-Taek Lim
- Institute of Sports and Arts Convergence (ISAC), Inha University, Incheon 22212, South Korea
- Waseda Institute for Sport Sciences, Waseda University, Saitama 341-0018, Japan
| | - Sunghwun Kang
- Laboratory of Exercise Physiology, College of Art, Culture and Engineering, Kangwon National University, Chuncheon-si 24341, South Korea
- Interdisciplinary Program in Biohealth-machinery convergence engineering, Kangwon National University, Chuncheon-si 24341, South Korea
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21
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Mitoma T, Maki J, Ooba H, Eto E, Takahashi K, Kondo T, Ikeda T, Sakamoto Y, Mitsuhashi T, Masuyama H. Protocol for a randomised, placebo-controlled, double-blinded clinical trial on the effect of oestrogen replacement on physical performance to muscle resistance exercise for older women with osteoarthritis of knee joint: the EPOK trial. BMC Geriatr 2023; 23:104. [PMID: 36800940 PMCID: PMC9938988 DOI: 10.1186/s12877-023-03828-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 02/15/2023] [Indexed: 02/20/2023] Open
Abstract
BACKGROUND Knee osteoarthritis (KOA) is highly prevalent in older women, and previous studies suggest the involvement of hormonal factors play a role in the pathogenesis of osteoarthritis. KOA causes musculoskeletal impairment, resulting in decreased physical activity, muscle mass, and strength, which leads to sarcopenia and further increases the burden on healthcare systems. Oestrogen replacement therapy (ERT) improves joint pain and muscle performance in early menopausal women. Muscle resistance exercise (MRE) is a non-pharmacological method that preserves the physical functions of patients with KOA. However, data on short-term oestrogen administration combined with MRE in postmenopausal women, especially in those aged > 65 years, are limited. Therefore, this study presents a protocol of a trial aimed to examine the synergistic effect of ERT and MRE on lower-limb physical performance in older women with KOA. METHODS We will conduct a double-blinded, randomised placebo-controlled trial in 80 Japanese women aged > 65 years living independently with knee pain. The participants will be randomly categorised into two groups: (1) 12-week MRE programme with transdermal oestrogen gel containing 0.54 mg oestradiol per push and (2) 12-week MRE programme with placebo gel. The primary outcome measured using the 30-s chair stand test, and secondary outcomes (body composition, lower-limb muscle strength, physical performance, self-reported measure of knee pain, and quality of life) will be measured at baseline, 3 months, and 12 months, and these outcomes will be analysed based on the intention-to-treat. DISCUSSION The EPOK trial is the first study to focus on the efficacy of ERT on MRE among women aged > 65 years with KOA. This trial will provide an effective MRE to prevent KOA-induced lower-limb muscle weakness, confirming the benefit of short-term oestrogen administration. TRIAL REGISTRATION Japan Registry of Clinical Trials: jRCTs061210062. Registered 17th December 2021, https://jrct.niph.go.jp/en-latest-detail/jRCTs061210062 .
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Affiliation(s)
- Tomohiro Mitoma
- Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Jota Maki
- Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Hikaru Ooba
- Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Eriko Eto
- Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Kasumi Takahashi
- Department of Obstetrics and Gynecology, Ochiai Hospital, Okayama, Japan
| | - Tsunemasa Kondo
- Department of Obstetrics and Gynecology, Ochiai Hospital, Okayama, Japan
| | - Tomohiro Ikeda
- Department of Rehabilitation Medicine, Okayama University, Okayama, Japan
| | - Yoko Sakamoto
- Center for Innovative Clinical Medicine, Okayama University, Okayama, Japan
| | | | - Hisashi Masuyama
- Department of Obstetrics and Gynecology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
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22
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Stamou MI, Colling C, Dichtel LE. Adrenal aging and its effects on the stress response and immunosenescence. Maturitas 2023; 168:13-19. [PMID: 36370489 PMCID: PMC10426230 DOI: 10.1016/j.maturitas.2022.10.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 10/14/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022]
Abstract
Normal aging is linked to various endocrine gland changes, including changes in the adrenal glands. Aging is linked to alterations of the hypothalamic-pituitary-adrenal (HPA) axis, including an increase in cortisol levels, a disruption of the negative cortisol feedback, and attenuation of cortisol's diurnal pattern. In addition, secretion of aldosterone and adrenal androgens [dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)] from the adrenal cortex decreases with aging. In this review, we describe normal adrenal function, the adrenal response to stress and immunomodulation in aging individuals as well as the effects of adrenal aging on body composition, metabolic profile, bone health and cognition.
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Affiliation(s)
- Maria I Stamou
- Endocrine Division, Massachusetts General Hospital, Boston, MA, USA.
| | - Caitlin Colling
- Endocrine Division, Massachusetts General Hospital, Boston, MA, USA
| | - Laura E Dichtel
- Endocrine Division, Massachusetts General Hospital, Boston, MA, USA
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23
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Bresilla D, Habisch H, Pritišanac I, Zarse K, Parichatikanond W, Ristow M, Madl T, Madreiter-Sokolowski CT. The sex-specific metabolic signature of C57BL/6NRj mice during aging. Sci Rep 2022; 12:21050. [PMID: 36473898 PMCID: PMC9726821 DOI: 10.1038/s41598-022-25396-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 11/29/2022] [Indexed: 12/12/2022] Open
Abstract
Due to intact reactive oxygen species homeostasis and glucose metabolism, C57BL/6NRj mice are especially suitable to study cellular alterations in metabolism. We applied Nuclear Magnetic resonance spectroscopy to analyze five different tissues of this mouse strain during aging and included female and male mice aged 3, 6, 12, and 24 months. Metabolite signatures allowed separation between the age groups in all tissues, and we identified the most prominently changing metabolites in female and male tissues. A refined analysis of individual metabolite levels during aging revealed an early onset of age-related changes at 6 months, sex-specific differences in the liver, and a biphasic pattern for various metabolites in the brain, heart, liver, and lung. In contrast, a linear decrease of amino acids was apparent in muscle tissues. Based on these results, we assume that age-related metabolic alterations happen at a comparably early aging state and are potentially associated with a metabolic switch. Moreover, identified differences between female and male tissues stress the importance of distinguishing between sexes when studying age-related changes and developing new treatment approaches. Besides, metabolomic features seem to be highly dependent on the genetic background of mouse strains.
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Affiliation(s)
- Doruntina Bresilla
- Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/VI, 8010, Graz, Austria
| | - Hansjoerg Habisch
- Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/VI, 8010, Graz, Austria
| | - Iva Pritišanac
- Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/VI, 8010, Graz, Austria
| | - Kim Zarse
- Laboratory of Energy Metabolism, Department of Health Sciences and Technology, Institute of Translational Medicine, ETH Zurich, Schorenstrasse 16, 8603, Schwerzenbach, Switzerland
| | - Warisara Parichatikanond
- Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand
- Faculty of Pharmacy, Center of Biopharmaceutical Science for Healthy Ageing (BSHA), Mahidol University, Bangkok, 10400, Thailand
| | - Michael Ristow
- Laboratory of Energy Metabolism, Department of Health Sciences and Technology, Institute of Translational Medicine, ETH Zurich, Schorenstrasse 16, 8603, Schwerzenbach, Switzerland
| | - Tobias Madl
- Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/VI, 8010, Graz, Austria.
- BioTechMed-Graz, Graz, Austria.
| | - Corina T Madreiter-Sokolowski
- Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/VI, 8010, Graz, Austria.
- BioTechMed-Graz, Graz, Austria.
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24
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Schaupp A, Bidlingmaier M, Martini S, Reincke M, Schluessel S, Schmidmaier R, Drey M. Resistance training-induced improvement in physical function is not associated to changes in endocrine somatotropic activity in prefrail older adults. Arch Gerontol Geriatr 2022; 103:104792. [PMID: 36037722 DOI: 10.1016/j.archger.2022.104792] [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: 06/20/2022] [Revised: 08/02/2022] [Accepted: 08/13/2022] [Indexed: 11/02/2022]
Abstract
CONTEXT Resistance training improves muscle function in prefrail and frail elderly. The role of the somatotropic axis in this physiologic process remains unclear. Insulin-like growth factor I (IGF-I) and its associated proteins Insulin-like growth factor binding protein 3 (IGFBP3) and acid labile subunit (ALS) build a circulating ternary complex that mediates growth hormone (GH) effects on peripheral organs and can serve as a measure of endocrine somatotropic activity. OBJECTIVE The aim of this study was to assess the association between resistance training-induced changes in physical performance and basal levels of IGF-I, IGFBP-3 and ALS in prefrail older adults. METHODS 69 prefrail community-dwelling older adults, aged 65 to 94 years, were randomly assigned to a 12-week period of strength or power training or to a control group. The study was registered at clinicaltrials.gov as NCT00783159. Serum concentrations of IGF-I, IGFBP-3 and ALS were measured at rest before and after the intervention. Hormonal differences were examined in relation to changes in physical performance assessed by the Short Physical Performance Battery (SPPB). RESULTS While resistance training led to significant improvements in SPPB score it did not induce significant differences in somatotropic hormone concentrations. Pre- and post-intervention changes in IGF-I, IGFBP-3, ALS or IGF/IGFBP-3 molar ratio were not related to the intervention mode, even after adjustment for age, sex, nutritional status, as well as SPPB and hormone concentrations at baseline. CONCLUSION Training-induced improvements in physical performance in prefrail older adults were not associated with significant changes in endocrine somatotropic activity.
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Affiliation(s)
- Anna Schaupp
- Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität Munich, Ziemssenstraße 5, Munich 80336, Germany.
| | - Martin Bidlingmaier
- Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität Munich, Ziemssenstraße 5, Munich 80336, Germany
| | - Sebastian Martini
- Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität Munich, Ziemssenstraße 5, Munich 80336, Germany
| | - Martin Reincke
- Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität Munich, Ziemssenstraße 5, Munich 80336, Germany
| | - Sabine Schluessel
- Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität Munich, Ziemssenstraße 5, Munich 80336, Germany
| | - Ralf Schmidmaier
- Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität Munich, Ziemssenstraße 5, Munich 80336, Germany
| | - Michael Drey
- Department of Medicine IV, University Hospital, Ludwig-Maximilians-Universität Munich, Ziemssenstraße 5, Munich 80336, Germany
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Cruz Borbely KS, Marques ALX, Porto FL, Mendonça BS, Smaniotto S, Dos Santos Reis MD. Growth Hormone Stimulates Murine Macrophage Migration during Aging. Curr Aging Sci 2022; 15:266-273. [PMID: 35430985 DOI: 10.2174/1874609815666220415132815] [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: 11/25/2021] [Revised: 02/16/2022] [Accepted: 03/06/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Age-related impairments in macrophage functions have important consequences for the health of the elderly population. The aging process is also accompanied by a reduction in several hormones, including growth hormone (GH). Previous studies have shown that this hormone can affect macrophage activity in young individuals; however, the biological effects of GH stimulation on macrophages during aging have not yet been elucidated. OBJECTIVE The aim of this work was to investigate the in vitro effects of GH on peritoneal macrophages from aged mice. METHODS Peritoneal macrophages isolated from young (4 months-old) and old (12-15 months-old) mice were treated in vitro with 100 ng/mL of GH for 24 hours. After treatment, cells were analysed for cell morphology, reactive oxygen species (ROS) production, expression of integrins, cell adhesion to extracellular matrix molecules, and migration in transwell chambers. RESULTS Although GH-treated cells from old mice exhibited decreased ROS production, we did not observe the effects of GH on macrophage morphology or macrophage phagocytic activity in young and old mice-derived cell cultures. Macrophages from old mice had increased adhesion to laminin and fibronectin substrates, as did cells obtained from young mice treated with GH, but no change was observed in the expression of integrin receptors. Furthermore, cells from old mice exhibited increased migration compared to young mice and a significant increase in macrophage migration was observed under GH stimulation. CONCLUSION Our results showed that GH can interfere with the motility of macrophages from old mice, advancing our understanding of the interactions between the immune and neuroendocrine systems during aging.
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Affiliation(s)
| | - Aldilane Lays Xavier Marques
- Laboratory of Cell Biology, Institute of Health and Biological Sciences, Federal University of Alagoas, Maceió, Alagoas, Brazil
| | - Felipe Lima Porto
- Laboratory of Cell Biology, Institute of Health and Biological Sciences, Federal University of Alagoas, Maceió, Alagoas, Brazil
- Brazilian National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Alagoas, Brazil
| | - Beatriz Santana Mendonça
- Laboratory of Cell Biology, Institute of Health and Biological Sciences, Federal University of Alagoas, Maceió, Alagoas, Brazil
| | - Salete Smaniotto
- Laboratory of Cell Biology, Institute of Health and Biological Sciences, Federal University of Alagoas, Maceió, Alagoas, Brazil
- Brazilian National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Alagoas, Brazil
| | - Maria Danielma Dos Santos Reis
- Laboratory of Cell Biology, Institute of Health and Biological Sciences, Federal University of Alagoas, Maceió, Alagoas, Brazil
- Brazilian National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Alagoas, Brazil
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Hormonal Agents for the Treatment of Depression Associated with the Menopause. Drugs Aging 2022; 39:607-618. [PMID: 35908135 PMCID: PMC9355926 DOI: 10.1007/s40266-022-00962-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/14/2022] [Indexed: 11/29/2022]
Abstract
Perimenopause marks the transition from a woman’s reproductive stage to menopause. Usually occurring between 42 and 52 years of age, it is determined clinically by the onset of irregular menstrual cycles or variable cycle lengths. Women are at an increased risk of depression and anxiety during perimenopause and the menopausal transition. Depressive symptoms experienced in perimenopause are often more severe compared to pre- and post-menopause. During menopausal transition, the impact of fluctuating estrogen in the central nervous system (CNS) can have negative psychological effects for some women. Traditional first-line management of menopausal depression involves antidepressants, with modest outcomes. The positive effects of estrogen treatment in the CNS are becoming increasingly recognised, and hormonal therapy (HT) with estrogen may have a role in the treatment of menopausal depression. In this review we will outline the prevalence, impact and neurochemical basis of menopausal-associated depression, as well as hormone-based approaches that have increasing promise as effective treatments.
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Effects of GH on the Aging Process in Several Organs: Mechanisms of Action. Int J Mol Sci 2022; 23:ijms23147848. [PMID: 35887196 PMCID: PMC9318627 DOI: 10.3390/ijms23147848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 06/26/2022] [Accepted: 07/11/2022] [Indexed: 11/17/2022] Open
Abstract
In order to investigate the possible beneficial effects of GH administration on the aging process, 24-month-old rats of both sexes and 10-month-old SAMP8 mice were used. Male rats showed increased fat content and decreased lean body mass together with enhanced vasoconstriction and reduced vasodilation of their aortic rings compared to young adult animals. Chronic GH treatment for 10 weeks increased lean body mass and reduced fat weight together with inducing an enhancement of the vasodilatory response by increasing eNOS and a reduction of the constrictory responses. Old SAMP8 male mice also showed insulin resistance together with a decrease in insulin production by the endocrine pancreas and a reduced expression of differentiation parameters. GH treatment decreased plasma levels and increased pancreatic production of insulin and restored differentiation parameters in these animals. Ovariectomy plus low calcium diet in rabbits induced osteoporosis Titanium implants inserted into these rabbit tibiae showed after one month lesser bone to implant (BIC) surface and bone mineral density (BMD). Local application of GH in the surgical opening was able to increase BIC in the osteoporotic group. The hippocampus of old rats showed a reduction in the number of neurons and also in neurogenesis compared to young ones, together with an increase of caspases and a reduction of Bcl-2. GH treatment was able to enhance significantly only the total number of neurons. In conclusion, GH treatment was able to show beneficial effects in old animals on all the different organs and metabolic functions studied.
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Kohata M, Imai J, Izumi T, Yamamoto J, Kawana Y, Endo A, Sugawara H, Seiko J, Kubo H, Kawamura H, Sato T, Osaka S, Munakata Y, Asai Y, Kodama S, Takahashi K, Kaneko K, Katagiri H. Roles of FoxM1-driven basal β-cell proliferation in maintenance of β-cell mass and glucose tolerance during adulthood. J Diabetes Investig 2022; 13:1666-1676. [PMID: 35633298 PMCID: PMC9533047 DOI: 10.1111/jdi.13846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/12/2022] [Accepted: 05/26/2022] [Indexed: 12/03/2022] Open
Abstract
Aims/Introduction Whether basal β‐cell proliferation during adulthood is involved in maintaining sufficient β‐cell mass, and if so, the molecular mechanism(s) underlying basal β‐cell proliferation remain unclear. FoxM1 is a critical transcription factor which is known to play roles in ‘adaptive’ β‐cell proliferation, which facilitates rapid increases in β‐cell mass in response to increased insulin demands. Therefore, herein we focused on the roles of β‐cell FoxM1 in ‘basal’ β‐cell proliferation under normal conditions and in the maintenance of sufficient β‐cell mass as well as glucose homeostasis during adulthood. Materials and Methods FoxM1 deficiency was induced specifically in β‐cells of 8‐week‐old mice, followed by analyzing its short‐ (2 weeks) and long‐ (10 months) term effects on β‐cell proliferation, β‐cell mass, and glucose tolerance. Results FoxM1 deficiency suppressed β‐cell proliferation at both ages, indicating critical roles of FoxM1 in basal β‐cell proliferation throughout adulthood. While short‐term FoxM1 deficiency affected neither β‐cell mass nor glucose tolerance, long‐term FoxM1 deficiency suppressed β‐cell mass increases with impaired insulin secretion, thereby worsening glucose tolerance. In contrast, the insulin secretory function was not impaired in islets isolated from mice subjected to long‐term β‐cell FoxM1 deficiency. Therefore, β‐cell mass reduction is the primary cause of impaired insulin secretion and deterioration of glucose tolerance due to long‐term β‐cell FoxM1 deficiency. Conclusions Basal low‐level proliferation of β‐cells during adulthood is important for maintaining sufficient β‐cell mass and good glucose tolerance and β‐cell FoxM1 underlies this mechanism. Preserving β‐cell FoxM1 activity may prevent the impairment of glucose tolerance with advancing age.
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Affiliation(s)
- Masato Kohata
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Junta Imai
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Tomohito Izumi
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - June Yamamoto
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Yohei Kawana
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Akira Endo
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Hiroto Sugawara
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Juno Seiko
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Hiroharu Kubo
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Hiroshi Kawamura
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Toshihiro Sato
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Shinichiro Osaka
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Yuichiro Munakata
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Yoichiro Asai
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Shinjiro Kodama
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Kei Takahashi
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Keizo Kaneko
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
| | - Hideki Katagiri
- Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 980-8575, Japan
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Shen W, He J, Hou T, Si J, Chen S. Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions. Aging Dis 2022; 13:1063-1091. [PMID: 35855334 PMCID: PMC9286910 DOI: 10.14336/ad.2021.1208] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 12/07/2021] [Indexed: 11/22/2022] Open
Abstract
Recently, there has been an increase in the incidence of malignant tumors among the older population. Moreover, there is an association between aging and cancer. During the process of senescence, the human body suffers from a series of imbalances, which have been shown to further accelerate aging, trigger tumorigenesis, and facilitate cancer progression. Therefore, exploring the junctions of aging and cancer and searching for novel methods to restore the junctions is of great importance to intervene against aging-related cancers. In this review, we have identified the underlying pathogenetic mechanisms of aging-related cancers by comparing alterations in the human body caused by aging and the factors that trigger cancers. We found that the common mechanisms of aging and cancer include cellular senescence, alterations in proteostasis, microbiota disorders (decreased probiotics and increased pernicious bacteria), persistent chronic inflammation, extensive immunosenescence, inordinate energy metabolism, altered material metabolism, endocrine disorders, altered genetic expression, and epigenetic modification. Furthermore, we have proposed that aging and cancer have common means of intervention, including novel uses of common medicine (metformin, resveratrol, and rapamycin), dietary restriction, and artificial microbiota intervention or selectively replenishing scarce metabolites. In addition, we have summarized the research progress of each intervention and revealed their bidirectional effects on cancer progression to compare their reliability and feasibility. Therefore, the study findings provide vital information for advanced research studies on age-related cancers. However, there is a need for further optimization of the described methods and more suitable methods for complicated clinical practices. In conclusion, targeting aging may have potential therapeutic effects on aging-related cancers.
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Affiliation(s)
- Weiyi Shen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China.
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang, China.
- Prevention and Treatment Research Center for Senescent Disease, Zhejiang University School of Medicine, Zhejiang, China
| | - Jiamin He
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China.
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang, China.
- Prevention and Treatment Research Center for Senescent Disease, Zhejiang University School of Medicine, Zhejiang, China
| | - Tongyao Hou
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China.
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang, China.
- Prevention and Treatment Research Center for Senescent Disease, Zhejiang University School of Medicine, Zhejiang, China
- Correspondence should be addressed to: Dr. Shujie Chen (), Dr. Jianmin Si () and Dr. Tongyao Hou (), Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China
| | - Jianmin Si
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China.
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang, China.
- Prevention and Treatment Research Center for Senescent Disease, Zhejiang University School of Medicine, Zhejiang, China
- Correspondence should be addressed to: Dr. Shujie Chen (), Dr. Jianmin Si () and Dr. Tongyao Hou (), Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China
| | - Shujie Chen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China.
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang, China.
- Prevention and Treatment Research Center for Senescent Disease, Zhejiang University School of Medicine, Zhejiang, China
- Correspondence should be addressed to: Dr. Shujie Chen (), Dr. Jianmin Si () and Dr. Tongyao Hou (), Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China
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Mele C, Mai S, Cena T, Pagano L, Scacchi M, Biondi B, Aimaretti G, Marzullo P. The pattern of TSH and fT4 levels across different BMI ranges in a large cohort of euthyroid patients with obesity. Front Endocrinol (Lausanne) 2022; 13:1029376. [PMID: 36313780 PMCID: PMC9606412 DOI: 10.3389/fendo.2022.1029376] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 09/26/2022] [Indexed: 11/13/2022] Open
Abstract
PURPOSE A multifold association relates the hypothalamo-pituitary-thyroid axis to body weight. The potential underlying mechanisms are incompletely understood. Further, the mild severity of obesity and the small proportion of individuals with obesity in so far published cohort studies provide little insights on metabolic correlates of thyroid function in obesity. METHODS We retrospectively enrolled 5009 adults with obesity (F/M, 3448/1561; age range, 18-87 years; BMI range, 30.0-82.7 kg/m2), without known thyroid disease in a study on TSH and fT4 levels, lipid profile, glucose homeostasis and insulin resistance, anthropometric parameters including BIA-derived fat mass (%FM) and fat-free mass (FFM). RESULTS The overall reference interval for TSH in our obese cohort was 0.58-5.07 mIU/L. As subgroups, females and non-smokers showed higher TSH levels as compared to their counterparts (p<0.0001 for both), while fT4 values were comparable between groups. There was a significant upward trend for TSH levels across incremental BMI classes in females, while the opposite trend was seen for fT4 levels in males (p<0.0001 for both). Expectedly, TSH was associated with %FM and FFM (p<0,0001 for both). TSH and fT4 showed correlations with several metabolic variables, and both declined with aging (TSH, p<0.0001; fT4, p<0.01). In a subgroup undergoing leptin measurement, leptin levels were positively associated with TSH levels (p<0.01). At the multivariable regression analysis, in the group as a whole, smoking habit emerged as the main independent predictor of TSH (β=-0.24, p<0.0001) and fT4 (β=-0.25, p<0.0001) levels. In non-smokers, %FM (β=0.08, p<0.0001) and age (β=-0.05, p<0.001) were the main significant predictors of TSH levels. In the subset of nonsmokers having leptin measured, leptin emerged as the strongest predictor of TSH levels (β=0.17, p<0.01). CONCLUSIONS Our study provides evidence of a gender- and smoking-dependent regulation of TSH levels in obesity.
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Affiliation(s)
- Chiara Mele
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
- *Correspondence: Chiara Mele,
| | - Stefania Mai
- Istituto Auxologico Italiano, IRCCS, Laboratory of Metabolic Research, S. Giuseppe Hospital, Piancavallo, Italy
| | - Tiziana Cena
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Loredana Pagano
- Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Massimo Scacchi
- Istituto Auxologico Italiano, IRCCS, Division of General Medicine, S. Giuseppe Hospital, Piancavallo, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Bernadette Biondi
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Gianluca Aimaretti
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Paolo Marzullo
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
- Istituto Auxologico Italiano, IRCCS, Laboratory of Metabolic Research, S. Giuseppe Hospital, Piancavallo, Italy
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Dugral E, Ordu G. Differences in Polysomnography Parameters of Women in the Post and Transitional Phases of Menopause. Cureus 2021; 13:e20570. [PMID: 35103149 PMCID: PMC8773356 DOI: 10.7759/cureus.20570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/21/2021] [Indexed: 11/05/2022] Open
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Zamponi V, Mazzilli R, Mazzilli F, Fantini M. Effect of sex hormones on human voice physiology: from childhood to senescence. Hormones (Athens) 2021; 20:691-696. [PMID: 34046877 PMCID: PMC8594207 DOI: 10.1007/s42000-021-00298-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 05/10/2021] [Indexed: 11/08/2022]
Abstract
The aim of the present literature review is to describe the influence of sex hormones on the human voice in physiological conditions. As a secondary sexual organ, the larynx is affected by sex hormones and may change considerably over the lifespan. In the current review, sex hormone-related voice modifications occurring during childhood, puberty, the menstrual cycle, pregnancy and senescence are described. The roles of sex hormones (including gonadotropins, testosterone, estrogen, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone-sulfate) underlying physiological voice changes are discussed, the main differences between males and females are explained and clinical implications are taken into account.
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Affiliation(s)
- Virginia Zamponi
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Rome, Italy.
| | - Rossella Mazzilli
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | - Fernando Mazzilli
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | - Marco Fantini
- Head and Neck Oncology Unit, Candiolo Cancer Institute, FPO IRCCS, Candiolo, Turin, Italy
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Fu S, Ping P, Li Y, Li B, Zhao Y, Yao Y, Zhang P. Centenarian longevity had inverse relationships with nutritional status and abdominal obesity and positive relationships with sex hormones and bone turnover in the oldest females. J Transl Med 2021; 19:436. [PMID: 34663361 PMCID: PMC8522151 DOI: 10.1186/s12967-021-03115-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 10/09/2021] [Indexed: 01/13/2023] Open
Abstract
Objective The number of older people is estimated to increase from 524 million in 2010 to 1.5 billion in 2050. The factors and models of human longevity and successful aging are questions that have intrigued individuals for thousands of years. For the first time, the current study was designed to investigate the relationships between sex hormones, bone turnover, abdominal obesity, nutritional status and centenarian longevity in the oldest females. Methods The China Hainan Centenarian Cohort Study was performed in 18 cities and counties of Hainan Province using standard methodology in 500 centenarian females and 237 oldest females aged between 80 and 99 years. Results Centenarians were inversely associated with the geriatric nutritional risk index [Exp(B) (95% CI): 0.901 (0.883–0.919)] and abdominal obesity [Exp(B) (95% CI): 0.719 (0.520–0.996)] and positively associated with prolactin [Exp(B) (95% CI): 1.073 (1.044–1.103)], progesterone [Exp(B) (95% CI): 44.182 (22.036–88.584)], estradiol [Exp(B) (95% CI): 1.094 (1.071–1.119)], osteocalcin [Exp(B) (95% CI): 1.041 (1.028–1.054)], β-crossLaps [Exp(B) (95% CI): 63.141 (24.482–162.848)] and parathyroid [Exp(B) (95% CI): 1.022 (1.013–1.031)] hormone levels (P < 0.05 for all). The geriatric nutritional risk index and abdominal obesity were inversely associated with luteinizing hormone [β coefficient (95% CI): − 0.001 (− 0.002 to 0.001)]; Exp(B) (95% CI): 0.985 (0.974–0.996)], follicle-stimulating hormone [β coefficient (95% CI): 0.000 (− 0.001 to 0.000)]; Exp(B) (95% CI): 0.990 (0.985–0.996)], osteocalcin [β coefficient (95% CI): − 0.001 (− 0.001 to 0.000)]; Exp(B) (95% CI): 0.987(0.977–0.997)] and β-crossLaps [β coefficient (95% CI): − 0.100 (− 0.130 to 0.071)]; Exp(B) (95% CI): 0.338 (0.166–0.689)] levels (P < 0.05 for all). Conclusions Centenarian longevity had inverse relationships with nutritional status and abdominal obesity and positive relationships with sex hormones and bone turnover. Nutritional status and abdominal obesity had inverse relationships with sex hormones and bone turnover. Increased sex hormones and bone turnover may be representative of centenarian longevity. Optimizing nutritional status and avoiding abdominal obesity may increase sex hormones and bone turnover and promote centenarian longevity and successful aging.
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Affiliation(s)
- Shihui Fu
- Cardiology Department, Hainan Hospital of Chinese People's Liberation Army General Hospital, Sanya, China. .,Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Ping Ping
- Pharmacy Department, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yulong Li
- Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Bo Li
- Cardiology Department, Hainan Hospital of Chinese People's Liberation Army General Hospital, Sanya, China
| | - Yali Zhao
- Central Laboratory, Hainan Hospital of Chinese People's Liberation Army General Hospital, Sanya, China.
| | - Yao Yao
- Center for Healthy Aging and Development Studies, National School of Development, Peking University, Beijing, China.
| | - Pei Zhang
- School of Life Science, Beijing Institute of Technology, Beijing, China.
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Ashraf R, Khan MS, Bhat MH, Shabir I, Rashid S, Majid S. Leptins: association and clinical correlation in pre-diabetics. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-01017-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Barros MPD, Bachi ALL, Santos JDMBD, Lambertucci RH, Ishihara R, Polotow TG, Caldo-Silva A, Valente PA, Hogervorst E, Furtado GE. The poorly conducted orchestra of steroid hormones, oxidative stress and inflammation in frailty needs a maestro: Regular physical exercise. Exp Gerontol 2021; 155:111562. [PMID: 34560197 DOI: 10.1016/j.exger.2021.111562] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 09/14/2021] [Accepted: 09/17/2021] [Indexed: 12/25/2022]
Abstract
This review outlines the various factors associated with unhealthy aging which includes becoming frail and dependent. With many people not engaging in recommended exercise, facilitators and barriers to engage with exercise must be investigated to promote exercise uptake and adherence over the lifespan for different demographics, including the old, less affluent, women, and those with different cultural-ethnic backgrounds. Governmental and locally funded public health messages and environmental facilitation (gyms, parks etc.) can play an important role. Studies have shown that exercise can act as a conductor to balance oxidative stress, immune and endocrine functions together to promote healthy aging and reduce the risk for age-related morbidities, such as cardiovascular disease and atherosclerosis, and promote cognition and mood over the lifespan. Like a classic symphony orchestra, consisting of four groups of related musical instruments - the woodwinds, brass, percussion, and strings - the aging process should also perform in harmony, with compassion, avoiding the aggrandizement of any of its individual parts during the presentation. This review discusses the wide variety of molecular, cellular and endocrine mechanisms (focusing on the steroid balance) underlying this process and their interrelationships.
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Affiliation(s)
- Marcelo Paes de Barros
- Institute of Physical Activity Sciences and Sports (ICAFE), MSc/PhD Interdisciplinary Program in Health Sciences, Cruzeiro do Sul University, 01506-000 São Paulo, Brazil.
| | - André Luís Lacerda Bachi
- Department of Otorhinolaryngology, ENT Lab, Federal University of São Paulo (UNIFESP), São Paulo 04025-002, Brazil; Post-Graduation Program in Health Sciences, Santo Amaro University (UNISA), São Paulo 04829-300, Brazil
| | | | | | - Rafael Ishihara
- Department of Biosciences, Federal University of São Paulo (UNIFESP), Santos 11015-020, SP, Brazil
| | - Tatiana Geraldo Polotow
- Institute of Physical Activity Sciences and Sports (ICAFE), MSc/PhD Interdisciplinary Program in Health Sciences, Cruzeiro do Sul University, 01506-000 São Paulo, Brazil
| | - Adriana Caldo-Silva
- University of Coimbra, Research Unit for Sport and Physical Activity (CIDAF, UID/PTD/04213/2019) at Faculty of Sport Science and Physical Education, (FCDEF-UC), Portugal
| | - Pedro Afonso Valente
- University of Coimbra, Research Unit for Sport and Physical Activity (CIDAF, UID/PTD/04213/2019) at Faculty of Sport Science and Physical Education, (FCDEF-UC), Portugal
| | - Eef Hogervorst
- Applied Cognitive Research National Centre for Sports and Exercise Medicine, Loughborough University, Loughborough, UK
| | - Guilherme Eustáquio Furtado
- Health Sciences Research Unit: Nursing (UICISA: E), Nursing School of Coimbra (ESEnfC), Coimbra, Portugal; Institute Polytechnic of Maia, Porto, Portugal; University of Coimbra, Research Unit for Sport and Physical Activity (CIDAF, UID/PTD/04213/2019) at Faculty of Sport Science and Physical Education, (FCDEF-UC), Portugal.
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Maity P, Singh K, Krug L, Koroma A, Hainzl A, Bloch W, Kochanek S, Wlaschek M, Schorpp-Kistner M, Angel P, Ignatius A, Geiger H, Scharffetter-Kochanek K. Persistent JunB activation in fibroblasts disrupts stem cell niche interactions enforcing skin aging. Cell Rep 2021; 36:109634. [PMID: 34469740 DOI: 10.1016/j.celrep.2021.109634] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 06/15/2021] [Accepted: 08/09/2021] [Indexed: 01/02/2023] Open
Abstract
Fibroblasts residing in the connective tissues constitute the stem cell niche, particularly in organs such as skin. Although the effect of fibroblasts on stem cell niches and organ aging is an emerging concept, the underlying mechanisms are largely unresolved. We report a mechanism of redox-dependent activation of transcription factor JunB, which, through concomitant upregulation of p16INK4A and repression of insulin growth factor-1 (IGF-1), initiates the installment of fibroblast senescence. Fibroblast senescence profoundly disrupts the metabolic and structural niche, and its essential interactions with different stem cells thus enforces depletion of stem cells pools and skin tissue decline. In fact, silencing of JunB in a fibroblast-niche-specific manner-by reinstatement of IGF-1 and p16 levels-restores skin stem cell pools and overall skin tissue integrity. Here, we report a role of JunB in the control of connective tissue niche and identified targets to combat skin aging and associated pathologies.
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Affiliation(s)
- Pallab Maity
- Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany; Aging Research Center (ARC), 89081 Ulm, Germany.
| | - Karmveer Singh
- Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany; Aging Research Center (ARC), 89081 Ulm, Germany
| | - Linda Krug
- Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany
| | - Albert Koroma
- Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany; Aging Research Center (ARC), 89081 Ulm, Germany
| | - Adelheid Hainzl
- Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany
| | - Wilhelm Bloch
- Institute of Cardiology and Sports Medicine, Molecular and cellular Sports Medicine, German Sport University Cologne, 50933 Cologne, Germany
| | - Stefan Kochanek
- Department of Gene Therapy, University of Ulm, 89081 Ulm, Germany
| | - Meinhard Wlaschek
- Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany
| | - Marina Schorpp-Kistner
- Division of Signal Transduction and Growth Control, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany
| | - Peter Angel
- Division of Signal Transduction and Growth Control, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany
| | - Anita Ignatius
- Institute of Orthopaedic Research and Biomechanics, Ulm University, 89081 Ulm, Germany
| | - Hartmut Geiger
- Aging Research Center (ARC), 89081 Ulm, Germany; Institute of Molecular Medicine and Stem Cell Aging, Ulm University, 89081 Ulm, Germany; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA
| | - Karin Scharffetter-Kochanek
- Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany; Aging Research Center (ARC), 89081 Ulm, Germany.
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Abstract
Changing demographic trends have led to an increase in the overall geriatric trauma patient volume. Furthermore, the intersection of aging and injury can be problematic because geriatric patients have multiple comorbidities, geriatric-specific syndromes, and reduced physiological reserve. Despite mounting evidence that frail geriatric patients have inferior outcomes following trauma, very few studies have examined the effect of aging on the biological response to injury. In the present article, we review the current literature and explore the pathophysiological rationale underlying observed data, available evidence, and future directions on this topic.
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Abstract
Aging athletes face unique, increased adversities related to increased mobility and age-related spine issues, such as spinal stenosis, osteoporosis complicated by fragility fractures, and degenerative disk disease. This article covers various spine pathologies that aging athletes experience and ideal treatment of this population to allow safe return to activity.
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Affiliation(s)
- Pramod N Kamalapathy
- Department of Orthopaedics, University of Virginia, 400 Ray Hunt C. Drive, Charlottesville, VA 22903, USA
| | - Hamid Hassanzadeh
- Department of Orthopaedics, University of Virginia, 400 Ray Hunt C. Drive, Charlottesville, VA 22903, USA.
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Gueugneau M, Coudy-Gandilhon C, Chambon C, Verney J, Taillandier D, Combaret L, Polge C, Walrand S, Roche F, Barthélémy JC, Féasson L, Béchet D. Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men. Int J Mol Sci 2021; 22:4205. [PMID: 33921590 PMCID: PMC8074053 DOI: 10.3390/ijms22084205] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 04/08/2021] [Accepted: 04/15/2021] [Indexed: 12/12/2022] Open
Abstract
(1) Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be clarified. Herein we performed omic profiling to decipher in muscle which dominating processes are associated with healthy aging and metabolic syndrome in old men. (2) Methods: This study included 15 healthy young, 15 healthy old, and 9 old men with metabolic syndrome. Old men were selected from a well-characterized cohort, and each vastus lateralis biopsy was used to combine global transcriptomic and proteomic analyses. (3) Results: Over-representation analysis of differentially expressed genes (ORA) and functional class scoring of pathways (FCS) indicated that healthy aging was mainly associated with upregulations of apoptosis and immune function and downregulations of glycolysis and protein catabolism. ORA and FCS indicated that with metabolic syndrome the dominating biological processes were upregulation of proteolysis and downregulation of oxidative phosphorylation. Proteomic profiling matched 586 muscle proteins between individuals. The proteome of healthy aging revealed modifications consistent with a fast-to-slow transition and downregulation of glycolysis. These transitions were reduced with metabolic syndrome, which was more associated with alterations in NADH/NAD+ shuttle and β-oxidation. Proteomic profiling further showed that all old muscles overexpressed protein chaperones to preserve proteostasis and myofiber integrity. There was also evidence of aging-related increases in reactive oxygen species but better detoxifications of cytotoxic aldehydes and membrane protection in healthy than in metabolic syndrome muscles. (4) Conclusions: Most candidate proteins and mRNAs identified herein constitute putative muscle biomarkers of healthy aging and metabolic syndrome in old men.
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Affiliation(s)
- Marine Gueugneau
- Université Clermont Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000 Clermont-Ferrand, France; (M.G.); (C.C.-G.); (D.T.); (L.C.); (C.P.); (S.W.)
| | - Cécile Coudy-Gandilhon
- Université Clermont Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000 Clermont-Ferrand, France; (M.G.); (C.C.-G.); (D.T.); (L.C.); (C.P.); (S.W.)
| | - Christophe Chambon
- Metabolomic and Proteomic Exploration Facility, Université Clermont Auvergne, INRAE, 63000 Clermont-Ferrand, France;
| | - Julien Verney
- Laboratoire AME2P, Université Clermont Auvergne, 3533 Clermont-Ferrand, France;
| | - Daniel Taillandier
- Université Clermont Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000 Clermont-Ferrand, France; (M.G.); (C.C.-G.); (D.T.); (L.C.); (C.P.); (S.W.)
| | - Lydie Combaret
- Université Clermont Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000 Clermont-Ferrand, France; (M.G.); (C.C.-G.); (D.T.); (L.C.); (C.P.); (S.W.)
| | - Cécile Polge
- Université Clermont Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000 Clermont-Ferrand, France; (M.G.); (C.C.-G.); (D.T.); (L.C.); (C.P.); (S.W.)
| | - Stéphane Walrand
- Université Clermont Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000 Clermont-Ferrand, France; (M.G.); (C.C.-G.); (D.T.); (L.C.); (C.P.); (S.W.)
| | - Frédéric Roche
- Service de Physiologie Clinique et de l’Exercice, CHU Saint Etienne, 42055 Saint Etienne, France; (F.R.); (J.-C.B.)
- INSERM, SAINBIOSE, U1059, Dysfonction Vasculaire et Hémostase, Université Jean-Monnet, 42055 Saint-Etienne, France
| | - Jean-Claude Barthélémy
- Service de Physiologie Clinique et de l’Exercice, CHU Saint Etienne, 42055 Saint Etienne, France; (F.R.); (J.-C.B.)
- INSERM, SAINBIOSE, U1059, Dysfonction Vasculaire et Hémostase, Université Jean-Monnet, 42055 Saint-Etienne, France
| | - Léonard Féasson
- Unité de Myologie, Service de Physiologie Clinique et de l’Exercice, Centre Référent Maladies Neuromusculaires Euro-NmD, 42000 CHU de Saint-Etienne, France;
- Laboratoire Interuniversitaire de Biologie de la Motricité, Université de Lyon, Université Jean Monnet Saint-Etienne, 69000 Lyon, France
| | - Daniel Béchet
- Université Clermont Auvergne, INRAE, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000 Clermont-Ferrand, France; (M.G.); (C.C.-G.); (D.T.); (L.C.); (C.P.); (S.W.)
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Frandsen J, Amaro-Gahete FJ, Landgrebe A, Dela F, Ruiz JR, Helge JW, Larsen S. The influence of age, sex and cardiorespiratory fitness on maximal fat oxidation rate. Appl Physiol Nutr Metab 2021; 46:1241-1247. [PMID: 33848440 DOI: 10.1139/apnm-2021-0080] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Fat oxidation decreases with age, yet no studies have previously investigated if aging affects the maximal fat oxidation rate (MFO) during exercise in men and women differently. We hypothesized that increased age would be associated with a decline in MFO and this would be more pronounced in women due to menopause, compared with men. In this cross-sectional study design, 435 (247/188, male/female) subjects of varying ages performed a DXA scan, a submaximal graded exercise test and a maximal oxygen uptake test, to measure MFO and cardiorespiratory fitness (CRF) by indirect calorimetry. Subjects were stratified into 12 groups according to sex (male/female), age (<45, 45-55 and >55 years), CRF (below average and above average). Women aged <45 years had a higher MFO relative to fat free mass (FFM) (mg/min/kg) compared with men, regardless of CRF. However, there were no differences in MFO (mg/min/kg FFM) between men and women, in the groups aged between 45-55 and >55 years. In summary, we found that women aged <45 years display a higher MFO (mg/min/kg FFM) compared with men and that this sexual divergence is abolished after the age of 45 years. Novelty: Maximal fat oxidation rate is higher in young women compared with men. This sex-related difference is attenuated after the age of 45 years. Cardiorespiratory fitness does not influence this sex-related difference.
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Affiliation(s)
- J Frandsen
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health, University of Copenhagen, Copenhagen, Denmark
| | - F J Amaro-Gahete
- Department of Medical Physiology, School of Medicine, University of Granada, 18071 Granada, Spain.,PROmoting FITness and Health through Physical Activity Research Group (PROFITH), Sport and Health University Research Institute (iMUDS), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, 18071 Granada, Spain
| | - A Landgrebe
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health, University of Copenhagen, Copenhagen, Denmark
| | - F Dela
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health, University of Copenhagen, Copenhagen, Denmark.,Department of Geriatrics, Bispebjerg University Hospital, Copenhagen, Denmark
| | - J R Ruiz
- PROmoting FITness and Health through Physical Activity Research Group (PROFITH), Sport and Health University Research Institute (iMUDS), Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, 18071 Granada, Spain
| | - J W Helge
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health, University of Copenhagen, Copenhagen, Denmark
| | - S Larsen
- Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health, University of Copenhagen, Copenhagen, Denmark.,Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
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Swimming as Treatment for Osteoporosis: A Systematic Review and Meta-analysis. BIOMED RESEARCH INTERNATIONAL 2021; 2020:6210201. [PMID: 32509864 PMCID: PMC7245678 DOI: 10.1155/2020/6210201] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Revised: 02/16/2020] [Accepted: 03/11/2020] [Indexed: 01/06/2023]
Abstract
Osteoporosis is a chronic disease that seriously affects human health and quality of life. This study is aimed at determining whether swimming had an effect on the bone mineral density (BMD) of the spine and femoral neck in postmenopausal and premenopausal osteoporosis patients. We retrieved relevant literature and analyzed data from randomized controlled trials to assess the effect of swimming on BMD in postmenopausal and premenopausal women. Relevant studies, with no language restrictions, from inception to September 2019, were retrieved from the PubMed, Cochrane, EMBASE, and EBSCO databases independently by two investigators. The keywords used for the literature search were “osteoporosis” and “swimming.” The main results included BMD and T-score. We searched 256 relevant articles and finally screened five articles, including 263 participants. Lumbar spine density was mentioned in three articles. Although the heterogeneity of lumbar vertebral density is moderate, the analysis of swimmers to nonswimmers shows that the lumbar vertebral density in swimmers is improved [heterogeneity: chi2 = 5.16, df = 2 (P = 0.08); I2 = 61%]. We analyzed the following heterogeneous subgroups: subgroup 1 (3–6 hours) and subgroup 2 (<3 hours). The BMD in subgroup 1 was significantly higher than that in the placebo, while no effect on BMD was found in subgroup 2 [heterogeneity: chi2 = 0.15, df = 3 (P = 0.70); I2 = 0%]. According to the current evidence, swimming may improve the BMD of postmenopausal women participants, if the swimming time is between 3 and 6 hours, especially in long-term swimmers. However, the effectiveness of swimming does require further investigation.
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Ferrari U, Schmidmaier R, Jung T, Reincke M, Martini S, Schoser B, Bidlingmaier M, Drey M. IGF-I/IGFBP3/ALS Deficiency in Sarcopenia: Low GHBP Suggests GH Resistance in a Subgroup of Geriatric Patients. J Clin Endocrinol Metab 2021; 106:e1698-e1707. [PMID: 33378445 DOI: 10.1210/clinem/dgaa972] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Indexed: 11/19/2022]
Abstract
CONTEXT Definition of etiological subgroups of sarcopenia may help to develop targeted treatments. insulin like growth factor-I (IGF-I), Insulinlike growth factor binding protein 3 (IGFBP3), and acid labile subunit (ALS) build a ternary complex that mediates growth hormone (GH) effects on peripheral organs, such as muscle. Low GH binding protein (GHBP) as a marker of GH receptor number would hint toward GH resistance. OBJECTIVE We aimed to analyze the association of IGF-I, IGFBP3, and ALS with sarcopenia. STUDY PARTICIPANTS AND SETTING A total of 131 consecutively recruited patients of a geriatric ward were included in a single-center cross-sectional analysis; the nonsarcopenic patients served as controls. METHODS Measures included sarcopenia status by hand-grip strength measurement and Skeletal Muscle Index (SMI); IGF-I, IGFBP3, ALS, GH, GHBP; body mass index (BMI); Activity of Daily Living (ADL); Mini-Mental State Examination (MMSE); routine laboratory parameters; and statistical regression modeling. RESULTS Compared with controls, sarcopenic patients did not differ regarding age, sex, ADL, MMSE, C-reactive protein, glomerular filtration rate, and albumin serum concentrations. However, sarcopenic patients had significantly lower IGF-I, IGFBP3, and ALS. IGF-I and ALS associated significantly with sarcopenia and low hand-grip strength, even after adjustment for age, sex, BMI, and albumin, but not with low SMI. GHBP serum was low in sarcopenic patients, but normal in geriatric patients without sarcopenia. Over 60% of patients with IGF-I/ALS deficiency patients showed GH resistance. CONCLUSIONS Our data suggest that in geriatric patients, low IGF-I/IGFBP3/ALS could be evaluated for causative connection of the sarcopenia spectrum. Low GHBP points toward potential GH resistance as one possible explanation of this deficiency.
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Affiliation(s)
- Uta Ferrari
- Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
| | - Ralf Schmidmaier
- Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
| | - Theresa Jung
- Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
| | - Martin Reincke
- Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
| | - Sebastian Martini
- Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
| | - Benedikt Schoser
- Friedrich-Baur-Institute, Department of Neurology, University Hospital, LMU Munich, Munich, Germany
| | | | - Michael Drey
- Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
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Hallmarks of environmental insults. Cell 2021; 184:1455-1468. [PMID: 33657411 DOI: 10.1016/j.cell.2021.01.043] [Citation(s) in RCA: 213] [Impact Index Per Article: 53.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/15/2021] [Accepted: 01/25/2021] [Indexed: 02/07/2023]
Abstract
Environmental insults impair human health around the world. Contaminated air, water, soil, food, and occupational and household settings expose humans of all ages to a plethora of chemicals and environmental stressors. We propose eight hallmarks of environmental insults that jointly underpin the damaging impact of environmental exposures during the lifespan. Specifically, they include oxidative stress and inflammation, genomic alterations and mutations, epigenetic alterations, mitochondrial dysfunction, endocrine disruption, altered intercellular communication, altered microbiome communities, and impaired nervous system function. They provide a framework to understand why complex mixtures of environmental exposures induce severe health effects even at relatively modest concentrations.
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Pataky MW, Young WF, Nair KS. Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications. Mayo Clin Proc 2021; 96:788-814. [PMID: 33673927 PMCID: PMC8020896 DOI: 10.1016/j.mayocp.2020.07.033] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 06/01/2020] [Accepted: 07/02/2020] [Indexed: 02/07/2023]
Abstract
Increased life expectancy combined with the aging baby boomer generation has resulted in an unprecedented global expansion of the elderly population. The growing population of older adults and increased rate of age-related chronic illness has caused a substantial socioeconomic burden. The gradual and progressive age-related decline in hormone production and action has a detrimental impact on human health by increasing risk for chronic disease and reducing life span. This article reviews the age-related decline in hormone production, as well as age-related biochemical and body composition changes that reduce the bioavailability and actions of some hormones. The impact of hormonal changes on various chronic conditions including frailty, diabetes, cardiovascular disease, and dementia are also discussed. Hormone replacement therapy has been attempted in many clinical trials to reverse and/or prevent the hormonal decline in aging to combat the progression of age-related diseases. Unfortunately, hormone replacement therapy is not a panacea, as it often results in various adverse events that outweigh its potential health benefits. Therefore, except in some specific individual cases, hormone replacement is not recommended. Rather, positive lifestyle modifications such as regular aerobic and resistance exercise programs and/or healthy calorically restricted diet can favorably affect endocrine and metabolic functions and act as countermeasures to various age-related diseases. We provide a critical review of the available data and offer recommendations that hopefully will form the groundwork for physicians/scientists to develop and optimize new endocrine-targeted therapies and lifestyle modifications that can better address age-related decline in heath.
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Affiliation(s)
- Mark W Pataky
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN
| | - William F Young
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN
| | - K Sreekumaran Nair
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN.
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Lasigliè D. Sirtuins and the prevention of immunosenescence. VITAMINS AND HORMONES 2021; 115:221-264. [PMID: 33706950 DOI: 10.1016/bs.vh.2020.12.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Aging of hematopoietic stem cells (HSCs) has been largely described as one underlying cause of senescence of the immune-hematopoietic system (immunosenescence). A set of well-defined hallmarks characterizes aged HSCs contributing to unbalanced hematopoiesis and aging-associated functional alterations of both branches of the immune system. In this chapter, the contribution of sirtuins, a family of conserved NAD+ dependent deacetylases with key roles in metabolism, genome integrity, aging and lifespan, to immunosenescence, will be addressed. In particular, the role of SIRT6 will be deeply analyzed highlighting a multifaceted part of this deacetylase in HSCs aging as well as in the immunosenescence of dendritic cells (DCs). These and other emerging data are currently paving the way for future design and development of rejuvenation means aiming at rescuing age-related changes in immune function in the elderly and combating age-associated hematopoietic diseases.
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Affiliation(s)
- Denise Lasigliè
- Istituto Comprensivo "Franco Marro", Ministero dell'Istruzione Ministero dell'Università e della Ricerca (M.I.U.R), Villar Perosa, TO, Italy.
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Connective Tissue and Fibroblast Senescence in Skin Aging. J Invest Dermatol 2021; 141:985-992. [PMID: 33563466 DOI: 10.1016/j.jid.2020.11.010] [Citation(s) in RCA: 148] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 10/28/2020] [Accepted: 11/11/2020] [Indexed: 02/06/2023]
Abstract
There is increasing evidence that skin aging is significantly enforced by the accumulation of senescent dermal fibroblasts. Various stressors damaging macromolecules inside and outside fibroblasts are responsible. In addition, NK cells fail to adequately remove senescent (SEN) fibroblasts from tissues. SEN fibroblasts by the release of the proinflammatory, tissue degrading senescent-associated secretory phenotype factors and vesicles with distinct cargo impact on their endogenous niche and spread senescence and skin aging. In this review, we will further discuss less noticed facets, including the plasticity of distinct dermal fibroblast phenotypes, the underestimated impact of the extracellular matrix itself, and the depletion of fibroblast subsets on skin homeostasis and aging.
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Mikkelsen MB, Tramm G, Zachariae R, Gravholt CH, O’Toole MS. A systematic review and meta-analysis of the effect of emotion regulation on cortisol. COMPREHENSIVE PSYCHONEUROENDOCRINOLOGY 2021; 5:100020. [PMID: 35754452 PMCID: PMC9216322 DOI: 10.1016/j.cpnec.2020.100020] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Accepted: 12/07/2020] [Indexed: 12/28/2022] Open
Abstract
It is generally acknowledged that hormones are implicated in socioemotional behavior, yet little is known about the role of hormones in the context of emotion regulation. The aims of the present review and meta-analysis were to review and synthesize the available evidence pertaining to the effect of emotion regulation instructions on hormones, and to investigate whether this effect varies according to: type of hormone, context (e.g., emotion-induction procedure), emotion regulation characteristics (e.g., emotion regulation strategy), and presence and type of psychiatric disorder. PubMed, PsycINFO, and CINAHL were searched for experimental studies assessing the effect of instructed emotion regulation on levels of hormones (i.e., testosterone, cortisol, oxytocin, estradiol, and vasopressin) in physically healthy adults. The literature search yielded 17 relevant studies, 16 investigating cortisol and one investigating testosterone. Of these, 12 cortisol studies had eligible data for the meta-analysis. The results of the meta-analysis indicated no statistically significant effect of receiving an emotion regulation instruction compared with receiving no instruction on the cortisol response to subsequent emotion induction (g = −0.05, p = .48). However, within-person comparisons of change from an unregulated response to a regulated response indicated a significant change in cortisol levels (g = 0.18, p = .03) consistent with the specified regulation goal (i.e., either up- or downregulation). No statistically significant effects were found in subgroup meta-analyses conducted according to context, emotion regulation characteristics or psychiatric disorders. Taken together, the findings indicate that emotion-induction procedures are associated with increases in cortisol that may subsequently return to equilibrium regardless of emotion-regulation instructions. Based on the large gaps in research (e.g., few studies investigated other hormones than cortisol, few studies included self-report measures of emotions) identified in the present review, we conclude that the effect of emotion regulation on hormones remains poorly understood. Prospero registration CRD42020157336.
Research on the effect of emotion regulation on hormones has focused on cortisol. Emotion regulation does not influence cortisol responses to emotion induction. Psychological confounders have received little attention in the reviewed research. The effect of emotion regulation on hormones remains poorly understood.
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Jeon YK, Shin MJ, Saini SK, Custodero C, Aggarwal M, Anton SD, Leeuwenburgh C, Mankowski RT. Vascular dysfunction as a potential culprit of sarcopenia. Exp Gerontol 2020; 145:111220. [PMID: 33373710 DOI: 10.1016/j.exger.2020.111220] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 12/17/2020] [Accepted: 12/18/2020] [Indexed: 02/08/2023]
Abstract
Aging-related changes to biological structures such as cardiovascular and musculoskeletal systems contribute to the development of comorbid conditions including cardiovascular disease and frailty, and ultimately lead to premature death. Although, frail older adults often demonstrate both cardiovascular and musculoskeletal comorbidities, the etiology of sarcopenia, and especially the contribution of cardiovascular aging is unclear. Aging-related vascular calcification is prevalent in older adults and is a known risk factor for cardiovascular disease and death. The effect vascular calcification has on function during aging is not well understood. Emerging findings suggest vascular calcification can impact skeletal muscle perfusion, negatively affecting nutrient and oxygen delivery to skeletal muscle, ultimately accelerating muscle loss and functional decline. The present review summarizes existing evidence on the biological mechanisms linking vascular calcification with sarcopenia during aging.
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Affiliation(s)
- Yun Kyung Jeon
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA; Division of Endocrinology and Metabolism, Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Myung Jun Shin
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA; Department of Rehabilitation Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Sunil Kumar Saini
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA
| | - Carlo Custodero
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA; Dipartimento Interdisciplinare di Medicina, Clinica Medica Cesare Frugoni, University of Bari Aldo Moro, Bari, Italy
| | - Monica Aggarwal
- Department of Medicine, Division of Cardiovascular Medicine, University of Florida, FL, USA
| | - Stephen D Anton
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA
| | | | - Robert T Mankowski
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA.
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Tidball JG, Flores I, Welc SS, Wehling-Henricks M, Ochi E. Aging of the immune system and impaired muscle regeneration: A failure of immunomodulation of adult myogenesis. Exp Gerontol 2020; 145:111200. [PMID: 33359378 DOI: 10.1016/j.exger.2020.111200] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 11/17/2020] [Accepted: 12/08/2020] [Indexed: 12/16/2022]
Abstract
Skeletal muscle regeneration that follows acute injury is strongly influenced by interactions with immune cells that invade and proliferate in the damaged tissue. Discoveries over the past 20 years have identified many of the key mechanisms through which myeloid cells, especially macrophages, regulate muscle regeneration. In addition, lymphoid cells that include CD8+ T-cells and regulatory T-cells also significantly affect the course of muscle regeneration. During aging, the regenerative capacity of skeletal muscle declines, which can contribute to progressive loss of muscle mass and function. Those age-related reductions in muscle regeneration are accompanied by systemic, age-related changes in the immune system, that affect many of the myeloid and lymphoid cell populations that can influence muscle regeneration. In this review, we present recent discoveries that indicate that aging of the immune system contributes to the diminished regenerative capacity of aging muscle. Intrinsic, age-related changes in immune cells modify their expression of factors that affect the function of a population of muscle stem cells, called satellite cells, that are necessary for normal muscle regeneration. For example, age-related reductions in the expression of growth differentiation factor-3 (GDF3) or CXCL10 by macrophages negatively affect adult myogenesis, by disrupting regulatory interactions between macrophages and satellite cells. Those changes contribute to a reduction in the numbers and myogenic capacity of satellite cells in old muscle, which reduces their ability to restore damaged muscle. In addition, aging produces changes in the expression of molecules that regulate the inflammatory response to injured muscle, which also contributes to age-related defects in muscle regeneration. For example, age-related increases in the production of osteopontin by macrophages disrupts the normal inflammatory response to muscle injury, resulting in regenerative defects. These nascent findings represent the beginning of a newly-developing field of investigation into mechanisms through which aging of the immune system affects muscle regeneration.
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Affiliation(s)
- James G Tidball
- Molecular, Cellular & Integrative Physiology Program, University of California, Los Angeles, CA, United States of America; Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, United States of America; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, United States of America.
| | - Ivan Flores
- Molecular, Cellular & Integrative Physiology Program, University of California, Los Angeles, CA, United States of America
| | - Steven S Welc
- Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, United States of America; Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, United States of America
| | - Michelle Wehling-Henricks
- Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, United States of America
| | - Eisuke Ochi
- Hosei University, Faculty of Bioscience and Applied Chemistry, 3-7-2, Kajino, Koganei, Tokyo 184-8584, Japan
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Harada K, Hanayama Y, Obika M, Itoshima K, Okada K, Otsuka F. Involvement of serum dehydroepiandrosterone sulfate in erythropoietic activity. Aging Male 2020; 23:756-763. [PMID: 30905228 DOI: 10.1080/13685538.2019.1592151] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
PURPOSE The aim of the present study was to determine how age-related decreases in serum dehydroepiandrosterone sulfate (DHEAS) levels affect various physiological processes. METHODS We retrospectively reviewed the medical records of patients in whom serum DHEAS levels were measured in our department and assessed the relationships between serum DHEAS levels and various patient characteristics. RESULTS Among the 149 patients included in our analysis (mean age: 52.7 ± 17.6 years, range: 15-84 years), 54 (36.2%) were men. Serum DHEAS levels inversely correlated with age in men (R = -0.810, p < .01) and to a lesser extent in women (R = -0.391, p < .01). Of note, there were significant positive associations between DHEAS levels and hemoglobin (R = 0.317, p ≤ .01) and hematocrit (R = 0.324, p ≤ .01) levels, which were observed in men, but not in women. CONCLUSIONS Our study suggests that reduced DHEAS secretion inhibits erythropoietic activity in aging men, perhaps owing to the erythropoietic androgenic actions of DHEAS. Importantly, it suggests that the age-associated decline in DHEAS secretion might decrease erythropoietic activity in aging men. It is also possible that the adrenal cortex, the source of DHEAS, is dysfunctional in anemic men.
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Affiliation(s)
- Ko Harada
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yoshihisa Hanayama
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Mikako Obika
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Koichi Itoshima
- Department of Laboratory Medicine, Okayama University Hospital, Okayama, Japan
| | - Ken Okada
- Department of Laboratory Medicine, Okayama University Hospital, Okayama, Japan
| | - Fumio Otsuka
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
- Department of Laboratory Medicine, Okayama University Hospital, Okayama, Japan
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