The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

{"title":"Symposia Report of The Annual Biological Sciences Section Meeting of the Gerontological Society of America 2023, Tampa, Florida.","authors":"Blanka Rogina, Rozalyn Anderson, Nathan K LeBrasseur, Sean P Curran, Matthew J Yousefzadeh, Bhaswati Ghosh, Gustavo Duque, Susan Howlett, Steven Austad, Ilja Demuth, Denis Gerstorf, Justin Korfhage, David B Lombard, Peter Abadir, Kaare Christensen, James R Carey, Susan C Alberts, Fernando Campos, Juan Pablo Palavicini, Allyson Palmer, Justice Bell, Nathan Basisty, Rafael de Cabo, Ana Gomes, Vishwa Deep Dixit, Payel Sen, Joseph A Baur, Shin-Ichiro Imai, Xiaoling Li, Gregorio Valdez, Miranda E Orr, Scott Pletcher, Julie Andersen, Leanne Jones, David Castillo-Azofeida, Michael Bonaguidi, Yousin Suh, Francesca E Duncan, Anna Murray, Meng C Wang, Kristopher Burkewitz, Mike Henne, Kai Zhou, Mustapha Bouhrara, Dan Benjamini, Shannon Kolind, Keenan A Walker, David A Reiter, Douglas C Dean, Vera Gorbunova, Vadim N Gladyshev, Robert Palovics, Laura J Niedernhofer, Rong Fan, Andreas D Bueckle, Jennifer Hurley, Karyn A Esser, Pankaj Kapahi, Shogo Sato, Nisi Jiang, Sarah A Ashiqueali, Jose Diaz, Sidharth Prasad Mishra, Nuno Raimundo, Reema Banarjee, Richard Allsopp, Lindsay M Reynolds, Bohan Zhang, Paola Sebastiani, Stefano Monti, Nicholas Schork, Noa Rappaport","doi":"10.1093/gerona/glaf026","DOIUrl":"10.1093/gerona/glaf026","url":null,"abstract":"<p><p>The aging process is universal, and it is characterized by a progressive deterioration and decrease in physiological function leading to decline on the organismal level. Nevertheless, a number of genetic and nongenetic interventions have been described, which successfully extend healthspan and lifespan in different species. Furthermore, a number of clinical trials have been evaluating the feasibility of different interventions to promote human health. The goal of the annual Biological Sciences Section of the Gerontological Society of America meeting was to share current knowledge of different topics in aging research and provide a vision of the future of aging research. The meeting gathered international experts in diverse areas of aging research including basic biology, demography, and clinical and translational studies. Specific topics included metabolism, inflammaging, epigenetic clocks, frailty, senescence, neuroscience, stem cells, reproductive aging, inter-organelle crosstalk, comparative transcriptomics of longevity, circadian clock, metabolomics, and biodemography.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality Trends in Pre-COVID-19 and COVID-19 Eras Among Oldest Veterans.","authors":"Jessica Palmer, Maithri Kondapaka, Brock A Beamer, Tariq Siddiqui, John D Sorkin, Wilbur H Chen, Raya Elfadel Kheirbek","doi":"10.1093/gerona/glaf051","DOIUrl":"https://doi.org/10.1093/gerona/glaf051","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic has had a profound impact on older adults, particularly those with existing comorbidities. To inform targeted healthcare strategies for this heterogeneous group, this study seeks to analyze and compare mortality trends among various geriatric age groups within the Veterans Affairs (VA) Health Care System, both during the COVID-19 era and the pre-COVID era, while accounting for demographic and clinical factors such as age, gender, race, and comorbidities.</p><p><strong>Methods: </strong>A retrospective cohort study using Veterans Affairs Informatics and Computing Infrastructure (VINCI) data. Two samples were analyzed: Veterans alive during the pre-COVID era (January 2019 - December 2019) and during the COVID era (January 2020 - December 2020). Propensity score matching was used to control for age, sex, race, BMI, and comorbidities.</p><p><strong>Results: </strong>The primary outcome was mortality. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to compare mortality across age groups. Unmatched analyses, adjusted for age, sex, race, BMI, and comorbidities, showed that mortality significantly increased during the COVID era for age groups 70-79 (OR 1.38), 80-89 (OR 1.14), and 90-99 (OR 1.20), all with p-values < 0.0001. No significant increase was observed in centenarians (OR 1.103, 95% CI 0.90-1.35, p=0.345). Matched analysis confirmed these findings.</p><p><strong>Conclusions: </strong>In a large cohort of older Veterans, COVID-19 had a significant impact on mortality in older adults aged 70-99, highlighting the need for targeted public health interventions. The lack of significant increase in mortality for centenarians is notable and warrants further study to identify possible protective factors in this unique population.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association of Circulating Immune Cells with Cognitive Function, Brain Imaging, and Incident all-cause and Alzheimer's Dementia: The Framingham Offspring Study.","authors":"Yumeng Cao, Lindsay R Salvati, Jiachen Chen, Ahmed Ragab, Jesse Mez, Claudia L Satizabal, Michael L Alosco, Yuan Fang, Wei Qiao Qiu, Kathryn L Lunetta, Joanne M Murabito, Margaret F Doyle","doi":"10.1093/gerona/glaf067","DOIUrl":"https://doi.org/10.1093/gerona/glaf067","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence supports the central role of the immune system in brain health, yet little is known about the role of circulating immune cells and cognitive function or brain health in dementia-free populations. We investigated the association of 43 immune cells with cognitive function, structural brain imaging, and incident dementia in Framingham Heart Study Offspring participants.</p><p><strong>Methods: </strong>Immune cells were phenotyped by flow cytometry. Linear mixed effects models were used for cross-sectional associations between immune cells and four cognitive domain scores and 13 brain MRI measurements. Cox proportional hazards regression models tested the relationship between immune cells and time to dementia. Models were adjusted for age, sex, education, CMV status, and APOE genotype, with further adjustment for cardiovascular risk factors. Data was further stratified by CMV status.</p><p><strong>Results: </strong>Among 795 participants with cellular phenotyping, cognitive testing and brain imaging data (mean age 61, 52% women), there were no associations between immune cells and cognitive test scores. Several significant associations between immune cells and regional brain MRI measurements were observed. Higher CD8+ cells [CD8+CD45RO-CCR7-CD27-(Teff), CD8+CD45RA+CD28-CD57+(TEMRA), CD8+CD27-CD28-] associated with greater cerebrum gray and frontal gray matter volumes and inclusion of cardiovascular risk factors strengthened the association. Among CMV+ participants, CD8+TEMRA and CD8+Teff cells were significantly associated with higher total gray and frontal gray matter volumes. No significant associations were observed between immune cells and incident all-cause or Alzheimer's disease dementia.</p><p><strong>Conclusion: </strong>The pathobiology underpinning the associations between immune cells and brain volumes require further study and validation in diverse samples.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCB1 Gene Polymorphisms and Their Contribution to Cognitive Decline in Mild Cognitive Impairment: A Next-Generation Sequencing Study.","authors":"Omar Šerý, Kateřina Sheardová, Radka Dziedzinska, Tomáš Zeman, Martin Vyhnálek, Hana Marková, Jan Laczó, Jan Lochman, Kamila Vrzalová, Vladimir J Balcar, Jakub Hort","doi":"10.1093/gerona/glaf055","DOIUrl":"https://doi.org/10.1093/gerona/glaf055","url":null,"abstract":"<p><p>The ABCB1 gene, encoding the ATP-dependent translocase ABCB1, plays a crucial role in the clearance of amyloid-beta (Aβ) peptides and the transport of cholesterol, implicating it in the pathogenesis of Alzheimer's disease. The study aims to investigate the association between polymorphisms in the ABCB1 gene and cognitive decline in individuals with MCI, particularly focusing on language function. A longitudinal cohort study involving 1005 participants from the Czech Brain Aging Study was conducted. Participants included individuals with Alzheimer's disease, amnestic mild cognitive impairment (MCI), non-amnestic MCI, subjective cognitive decline, and healthy controls. Next-generation sequencing was utilized to analyze the entire ABCB1 gene. Cognitive performance was assessed using a comprehensive battery of neuropsychological tests, including the Boston Naming Test and the semantic verbal fluency test. Ten ABCB1 polymorphisms (rs55912869, rs56243536, rs10225473, rs10274587, rs2235040, rs12720067, rs12334183, rs10260862, rs201620488, rs28718458) were significantly associated with cognitive performance, particularly in language decline among amnestic MCI patients. In silico analyses revealed that some of these polymorphisms may affect the binding sites for transcription factors (HNF-3alpha, C/EBPβ, GR-alpha) and the generation of novel exonic splicing enhancers. Additionally, polymorphism rs55912869 was identified as a potential binding site for the microRNA hsa-mir-3163. Our findings highlight the significant role of ABCB1 polymorphisms in cognitive decline, particularly in language function, among individuals with amnestic MCI. These polymorphisms may influence gene expression and function through interactions with miRNAs, transcription factors, and alternative splicing mechanisms.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143757088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic Pathways of Inflammation and Mitochondrial Dysfunction are Related to Worsening Healthy Aging Index and Mortality.","authors":"Shanshan Yao, Megan M Marron, Qu Tian, Eleanor L Watts, Clary B Clish, Ravi V Shah, Venkatesh L Murthy, Anne B Newman","doi":"10.1093/gerona/glaf057","DOIUrl":"https://doi.org/10.1093/gerona/glaf057","url":null,"abstract":"<p><strong>Background: </strong>Metabolic-inflammatory states are central to multiorgan mechanisms of aging, but precise functional biomarkers of physiological aging remain less clear.</p><p><strong>Methods: </strong>In the Health, Aging and Body Composition study, we defined metabolomic profiles of the Healthy Aging Index (HAI), a composite of cardiovascular, lung, cognitive, metabolic, and renal function (0-10, with higher scores indicating poorer health) in a split set design from 2015 older participants (mean age 73.6 years; 50% women; 35% Black). We used standard regression to identify metabolomic correlates of Year 1 and Year 10 HAI, change in HAI over time, and mortality. A metabolite score of HAI was developed using LASSO regression.</p><p><strong>Results: </strong>We identified 42 metabolites consistently associated with Year 1 and Year 10 HAI, as well as change in HAI: 13 lipids, 4 amino acids, and 4 metabolites of other classes were associated with worse and worsening HAI while 20 lipids and 1 amino acid was associated with better and improving HAI. Most of these associations were no longer significant after additionally adjusting for inflammation biomarkers. A higher metabolite score of Year 1 HAI was associated with greater HAI deterioration over time (hold-out \"test\" set beta 0.40 [0.15-0.65]) and higher mortality (hold-out \"test\" set hazard ratio: 1.43 [1.23-1.67]).</p><p><strong>Conclusions: </strong>A multi-organ healthy aging phenotype was linked to lipid metabolites, suggesting potential pathways related to mitochondrial function, oxidative stress and inflammation. Metabolomics of HAI at older age were related to worsening health and mortality, suggesting potential links between metabolism and accelerated physiological aging.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship of multiple sensory impairments with physical performance in older adults in the Study of Muscle, Mobility and Aging.","authors":"Atalie C Thompson, Tyler Mansfield, Eileen Johnson, Peggy M Cawthon, Elsa S Strotmeyer, Jeff D Williamson, Steve Cummings, Theresa Mau, Stephen B Kritchevsky","doi":"10.1093/gerona/glaf065","DOIUrl":"https://doi.org/10.1093/gerona/glaf065","url":null,"abstract":"<p><strong>Background: </strong>Sensory and cognitive function can impact physical performance, but the relationship of multiple sensory impairments (SI) with mobility in older adults is not well understood. We hypothesized that severity and number of SIs would be associated with worse timed physical mobility performance, and that cognitive processing speed would mediate the association.</p><p><strong>Methods: </strong>Participants (N=832) were older adults (mean age 76.3+/-5.0 years; 59.4% women; 84.2% Non-Hispanic White) who completed tests of physical performance, cognitive function, and multiple sensory domains. Separate linear regression models examined the association of SI with 400m walk, expanded Short Physical Performance Battery (eSPPB), four-square step test (FSST), and stair climb test. Cognitive measures of executive function/processing speed (Digit Symbol Coding (DSC) and Trails Making Test (Trails) B) were tested as potential mediators of the relationship between SI and physical performance.</p><p><strong>Results: </strong>Each one-point decrement in SI scale was associated with slower 400m walking speed (β=-0.01 m/s, p=0.03), lower eSPPB score (β=-0.05 points, p<0.001), and longer FSST time (β=0.20 seconds, p=0.01), but there was no association with stair climb time. Using a causal mediation approach with DSC and Trails B as potential mediators, 47.9% of the association of SI with 400m walk was mediated, 43.8% of the association of SI with eSPPB, and 56.7% of the association of MSI with FSST.</p><p><strong>Conclusions: </strong>Greater SIs were associated with worse physical performance in older adults, and the association was partially mediated by measures of cognitive processing speed and executive function. Future studies should investigate the temporal relationship between SI, cognitive and physical function.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It's never too early, it's never too late: the potential of health behaviours for cardiovascular health in nonagenarians. Data from the Mugello Study.","authors":"Silvia Pancani, Gemma Lombardi, Francesco Sofi, Guido Pasquini, Federica Vannetti, Francesca Cecchi, Claudio Macchi","doi":"10.1093/gerona/glaf064","DOIUrl":"https://doi.org/10.1093/gerona/glaf064","url":null,"abstract":"<p><strong>Background: </strong>The Life's Essential 8 (LE8) is a composite metric including four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure). This study aimed to describe the cardiovascular health (CVH) metrics promoted by LE8 in nonagenarians and to investigate their relationship with mortality at five and ten years.</p><p><strong>Methods: </strong>This study was conducted within the framework of the Mugello Study, a longitudinal survey on nonagenarians living in the Mugello area (Tuscany, Italy). One-hundred and fifty-seven subjects (42 males and 115 females, median age 92 years) were administered a series of validated questionnaires and underwent instrumental examinations and blood withdrawal. CVH metrics were calculated according to LE8 guidelines. Physical activity and sleep duration were quantitatively estimated using a monitor device.</p><p><strong>Results: </strong>In the male group, after 5 and 10 years of follow-up, a higher Health Behaviour score was associated with a lower risk of all-cause mortality (HR: 0.963, p=0.005 and HR: 0.972, p=0.020; after 5 and 10 years). Differently, in the female group, no significant association was observed between the LE8 total score and sub-scores and different risk of mortality after 5 and 10 years from the interview.</p><p><strong>Conclusions: </strong>These findings highlight the importance of potentially modifiable behaviours in improving survival. They support resource investments to address the needs of individuals in this stage of life and encourage them to be empowered and actively engage in health-promoting behaviours.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of periodontitis with biological aging among US adults: An exploratory mediation analysis via lactate.","authors":"Huan Zhou, Yong Li, Di Miao, Jiayu Zhang, Lisa Yang, An Li, Ruoyan Cao","doi":"10.1093/gerona/glaf061","DOIUrl":"https://doi.org/10.1093/gerona/glaf061","url":null,"abstract":"<p><strong>Background: </strong>To investigate the potential role of lactate in the relationship between periodontitis and biological aging.</p><p><strong>Methods: </strong>Cross-sectional data from 9,652 participants in the National Health and Nutrition Examination Survey 2009-2014 were analyzed. Periodontitis was categorized based on the Centers for Disease Control and Prevention and American Academy of Periodontology (CDC/AAP) classification. Biological aging was assessed based on KDM-BA acceleration and PhenoAge acceleration, while lactate levels were assessed using lactate dehydrogenase (LDH). Weighted multivariable linear regression analyses were conducted to examine the association between periodontitis and biological aging. Additionally, exploratory mediation analyses were carried out to determine the mediating effect of LDH on this association.</p><p><strong>Results: </strong>Participants with moderate/severe periodontitis showed accelerated biological aging and higher serum LDH levels. Similarly, mean attachment loss (AL) and probing pocket depth (PPD) were positively associated with biological aging and serum LDH levels. Furthermore, serum LDH was found to mediate 8.4% and 3.8% of the associations between periodontitis and KDM-BA acceleration and PhenoAge acceleration, respectively. LDH also explained 11.0% and 4.4% of the association between mean PPD and KDM-BA acceleration and PhenoAge acceleration, respectively. However, the role of LDH in the relationship between mean AL and biological aging was not observed.</p><p><strong>Conclusion: </strong>These findings indicate that LDH, an enzyme that converts pyruvate to lactate, mediates the association between periodontitis and biological aging. However, additional longitudinal or interventional studies are needed to more effectively assess causality and confirm our findings.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mito-Modulatory Medication Use and Skeletal Muscle Bioenergetics Among Older Men and Women: the Study of Muscle, Mobility and Aging.","authors":"Howard J Phang, Jaclyn Bergstrom, Rabia S Atayee, Laura A Hart, Peggy M Cawthon, Terri Blackwell, Philip A Kramer, Giovanna Distefano, Erin E Kershaw, Steven R Cummings, Anthony J A Molina","doi":"10.1093/gerona/glaf063","DOIUrl":"https://doi.org/10.1093/gerona/glaf063","url":null,"abstract":"<p><strong>Background: </strong>The potential impacts of drug-induced modulation of mitochondrial function in humans remain unclear despite the high prevalence of \"mito-modulatory\" medication use among older adults. While these medications, such as statins and metformin, have undergone extensive characterization of their effects on mitochondrial function in vitro, the effects in humans are far more complex and poorly understood.</p><p><strong>Methods: </strong>This study uses data from the Study of Muscle, Mobility and Aging (SOMMA) to evaluate how mito-modulatory medication use is related to skeletal muscle bioenergetic capacity, measured by ex vivo high-resolution respirometry and in vivo phosphorus magnetic resonance spectroscopy in healthy older adults.</p><p><strong>Results: </strong>We found that mito-modulatory medication use was related to lower maximal complex I&II supported oxidative phosphorylation (Max OXPHOS), maximal electron transfer system capacity (Max ETS), and maximal ATP production capacity (ATP Max) in men, but not in women. We also found this to be dependent on the number of medications used, in which higher mito-modulatory medication load was associated with lower Max OXPHOS, Max ETS, and ATP Max.</p><p><strong>Conclusions: </strong>Our results provide greater insight into the potential clinical effects of mito-modulatory medication use and highlight the need to test the impact of these medications on mitochondrial function in randomized trials.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-associated increase in AT1R expression in human testis and its intervention effects on Leydig cell senescence in aged rodents.","authors":"Minye Zhao, Jinhua Wei, Yao Geng, Yang Zhang, Jie Zhao, Hong Yang, Wei Hua, Wei Li","doi":"10.1093/gerona/glaf004","DOIUrl":"https://doi.org/10.1093/gerona/glaf004","url":null,"abstract":"<p><p>The active peptide hormone Ang II (angiotensin II) mediates the vast majority of the RAS (renin-angiotensin system) action, mainly through activation of AT1R (Angiotensin II type-1 receptor). AT1R expression peaks in newborn males and decreases toward the adult age, and it is shown to exhibit an inhibitory effect on hCG (human chorionic gonadotropin)-stimulated steroidogenesis in LCs (Leydig cells), as well as an promoting effect on smooth muscle and endothelial cell senescence. However, whether hyperactivation of the AT1R signaling exerts any effects on Leydig cell senescence, which could provide insights into hypogonadism mechanisms for aging males, remains unexplored. We herein reported that AT1R expression was significantly upregulated in aged human and rat testes. Transgenic overexpression of AT1R in LCs mimicked multiple late-onset hypogonadism phenotypes, including acceleration of Leydig cell senescence, defective steroidogenesis and spermatogenesis, and increased inflammation and oxidative stress. One of the core biochemical events underpinning AT1R action was the AT1R-induced enhancement of the interaction between MDM2 (murine double minute 2) and the p65 subunit of NF-κB (nuclear factor-kappaB), consequently augmenting polyubiquitination and activation of p65, in a p38-dependent manner. Conversely, repression of AT1R activity ameliorated Leydig cell senescence and rescued testicular steroidogenesis in old rats. Together, forced expression of AT1R within the testicular interstitium potentiates aging-related traits in LCs, thereby leading to fertility impairment with defective steroidogenesis and spermatogenesis in male rodents. Our systematic analysis also indicates that blocking the Ang II/AT1R signal might be beneficial in intervening disorders of late-onset hypogonadism in old males.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}