The Journals of Gerontology Series A: Biological Sciences and Medical Sciences最新文献

{"title":"Does Lower Oxidative Capacity Influence the Relative Contributions of ATP-Producing Pathways During Muscular Work in Aging?","authors":"Zoe H Smith,Liam F Fitzgerald,Rajakumar Nagarajan,Kate L Hayes,Martin Meyerspeer,Alfredo L Lopez Kolkovsky,Jane A Kent","doi":"10.1093/gerona/glaf142","DOIUrl":"https://doi.org/10.1093/gerona/glaf142","url":null,"abstract":"Although the capacity of skeletal muscle to produce ATP via oxidative phosphorylation may decrease in some muscles in older age, the influence of a lower capacity on relative use of oxidative and non-oxidative ATP production pathways in vivo during contractions is unclear. To test the hypothesis that lower oxidative capacity would yield greater non-oxidative ATP production, 19 young (10F) and 17 older (9F) adults performed knee extensor muscle contractions in a 3-tesla magnetic resonance system. Phosphorus metabolites were used to calculate oxidative capacity (rate constant of phosphocreatine recovery; k PCr, s-1) and estimate the maximal rate of oxidative ATP production (Vmax, mM·s-1) following a 24-s dynamic contraction protocol. Next, ATP production (mM·s-1) by the creatine kinase reaction (ATPCK), glycolysis (ATPGLY), and oxidative phosphorylation (ATPOX) was determined during 4 min of dynamic muscle contractions. Proton spectroscopy of deoxymyoglobin was also acquired in a subset (n = 12) and used to calculate the cytosolic partial pressure of oxygen (PO2). Young muscle had a greater k PCr (0.023±0.005s-1, mean±SD) than older muscle (0.020±0.003s-1, p = 0.033). ATPCK, ATPGLY, and ATPOX were not different by group (p ≥ 0.129), but ATPOX as %Vmax was lower in younger than older muscle (55±14%, 71±10%, respectively, p < 0.001). Intracellular oxygen availability (PO2) was not different by group (young: 2.4±0.7 Torr, n = 7; older: 3.2±1.6 Torr, n = 5, p = 0.371). These new findings suggest a bioenergetic rigidity in older muscle, such that it adapts to the energetic demand by using oxidative ATP production at a greater percentage of capacity rather than switching to an increased use of non-oxidative ATP production.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533300","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":"Association of multimorbidity trajectories from early adulthood through middle age with middle-age physical function.","authors":"C Barrett Bowling,Richard Sloane,Richard A Faldowski,Carl Pieper,Tyson Brown,Erin E Dooley,Brett T Burrows,Ankeet S Bhatt,Donald M Lloyd-Jones,Cora E Lewis,Kelley Pettee Gabriel","doi":"10.1093/gerona/glaf140","DOIUrl":"https://doi.org/10.1093/gerona/glaf140","url":null,"abstract":"BACKGROUNDChronic conditions can develop early in the adult life course and accumulate at different rates. However, the association between multimorbidity trajectory groups from young adulthood and physical function in midlife has not been well studied.METHODSData are from 2,018 Coronary Artery Risk Development in Young Adults (CARDIA) study participants who completed a PROMIS Function Short Form and five physical performance tests (gait speed, grip strength, balance, chair stands, 6-minute-walk, composite score range 0-20, higher is better). Multimorbidity trajectory groups were previously identified using latent class growth models and characterized by the age of onset and rapidity of accumulation of conditions: (1) early-fifties, slow (E50S), (2) mid-forties, fast (M40F), (3) mid-thirties, fast (M30F), (4) late-twenties, slow (L20F), (5) mid-twenties, slow (M20S), and (6) mid-twenties, fast (M20F). The association of multimorbidity trajectory group with physical function scores in middle age were estimated using multiple linear regression.RESULTSAt the time of physical function measurement, participants had a mean age (SD) of 60.0 (3.6) years, 58.2% were female, and 44.4% were Black. Compared to participants in the E50S class, adjusted mean differences in the PROMIS score were -1.37, -1.44, -3.18, and -2.53 for those in the M40F, M30F, L20F, M20F, respectively (all p-values <0.01). Compared to E50S adjusted mean differences in the composite performance scores were -1.48, -0.44, and -1.51 for L20F, M20S, M20F, respectively (all p-values <0.05).CONCLUSIONSEarlier onset and more rapid accumulation of chronic conditions from early adulthood may identify those at risk for functional limitations in midlife.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"633 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520893","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":"Mental exertion causes impairments in multi-finger force deficit during a hand grip strength task in older adults.","authors":"Narges Kazemi,Hamidreza Barzegarpoor,Hamid Rajabi,Brian C Clark,Rana Fayazmilani","doi":"10.1093/gerona/glaf141","DOIUrl":"https://doi.org/10.1093/gerona/glaf141","url":null,"abstract":"BACKGROUNDThere has been growing interest in the interrelationship between age-related reductions in cognitive and motor function. To advance the understanding of this interrelationship, we sought to determine whether a mentally fatiguing task differentially effects hand grip motor function in older versus younger adults.METHODSYoung (n = 10, 33 ± 3 years) and older adults (n = 15, 69 ± 3 years) free of overt neurological disease and who did not report chronic fatigue symptoms participated in two testing sessions. During both sessions, participants had their composite grip strength (GS) and their multi-finger force deficit (MFFD) measured. The MFFD assays the degree of neural inactivation observed during a composite grip strength test. During one session participants completed a series of psychomotor vigilance tasks (PVT) to induce mental fatigue. The other session served as a control condition.RESULTSOlder adults exhibited an ∼18% reduction in composite GS associated with mental effort, which was significantly greater than that observed in young adults. Indirect neural activation, assessed via the MFFD, was reduced by approximately 22% in older adults during mental effort, which was significantly greater than the reduction observed in young adults.CONCLUSIONS: These findings indicate that mental exertion/fatigue results in decreased composite GS and increasing impairments in neural activation in older adults. No effect on indices of neuromuscular performance were observed in young adults. These findings suggest that neural mechanisms are heavily involved in the regulation of composite grip strength, and that the relative contribution of neural and muscular mechanisms of handgrip strength are state dependent in older adults.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504583","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":"Differences in Phenotypic and Functional Aging Trajectories Among People Aging with Disability and the U.S. General Population.","authors":"Seeun Park,Ivan Molton,Lisa Bratzke","doi":"10.1093/gerona/glaf136","DOIUrl":"https://doi.org/10.1093/gerona/glaf136","url":null,"abstract":"BACKGROUNDPeople aging with disability (PAwD) may experience distinct life course exposures that impact their aging trajectories, yet the extent to which these trajectories differ from those of the U.S. general population remains understudied. This study aimed to investigate the impact of long-term disability on phenotypic and functional aging trajectories, and assess the role of key demographic and social determinants on those trajectories.METHODSData from the 2006-2020 waves of the Health and Retirement Study were used. Phenotypic aging was measured by the metabolic dysfunction risk score (MDRS) and functional aging was operationalized through limitations in activities of daily living (ADL) and instrumental activities of daily living (IADL). Growth curve modeling was employed, adjusting for age, birth cohort, gender, race/ethnicity, and educational attainment.RESULTSA total of 7,234 were included in the analysis, comprising 873 PAwD and 6,361 individuals from the general population. Results suggested pronounced disparities in phenotypic and functional aging trajectories between groups, with compounded vulnerabilities among marginalized subgroups. PAwD exhibited significantly higher MDRS and ADL/IADL scores, with more rapid escalation over time, suggesting premature and accelerated aging. Racial/ethnic minorities and individuals with lower education faced intersecting disadvantages in both domains. Woman aging with disability exhibited marginally greater MDRS than men. Cohort-disability interaction revealed that older PAwD cohorts experienced steeper functional decline, while younger cohorts showed accelerated metabolic dysregulation.CONCLUSIONSThese findings highlight the imperative for inclusive public policies that address structural inequalities, particularly educational and racial disparities. Implementing preventative, disability-informed rehabilitative interventions is also essential to promote aging equity among PAwD.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521017","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":"Increased levels of Aβ40 in plasma is associated with severity of exposure to airborne pollutants at the World Trade Center: A cross-sectional study of neurological biomarkers.","authors":"Alissa Barber,Ryan Chacon,Frank D Mann,Minos Kritikos,Jaymie Meliker,Pei-Fen Kuan,Melissa A Carr,Xiaohua Yang,Sean A P Clouston,Benjamin J Luft","doi":"10.1093/gerona/glaf135","DOIUrl":"https://doi.org/10.1093/gerona/glaf135","url":null,"abstract":"World Trade Center (WTC) responders who were more severely exposed to the airborne pollution while working in rescue and recovery work would have heightened circulating levels of β-Amyloid (Aβ) levels in plasma. Plasma for 905 World Trade Center (WTC) responders was retrieved in 2019 and flash frozen and assayed using single molecule analysis to measure circulating levels of two subtypes of Aβ (Aβ40, Aβ42), alongside phosphorylated tau-181, glial fibrillary acidic protein, and neurofilament-light. Plasma data were linked to demographics, blood volume, apolipoprotein-ε4 status, and medical outcomes as well as, in a subsample, with neuroimaging-based measures of cortical thickness. Amyloidogenesis was measured using the ratio of observed/expected levels of Aβ40 and labeled Normalized Aβ40. Spearman's rho was used to examine correlations; generalized linear modeling was used to examine multivariable-adjusted associations. The average age of World Trade Center (WTC) responders was 55.98 years, and 73.9% had completed at least some college. Observed Aβ40 levels were 24.61% higher than expected values, and lower in minimally exposed WTC responders as compared to severely exposed WTC responders (17.26 versus 44.48%, P = 0.005). Results remained statistically significant upon adjusting for covariates (adjusted blood volume ratio = 1.11 [1.02-1.22] p = 0.019). Normalized Aβ40 levels were associated with higher measures of phosphorylated tau-181, Aβ42, glial fibrillary acidic protein, and neurofilament-light in serology as well as, in a subsample (n = 70), with reduced cortical thickness (rho = -0.29, p = 0.020). Increased amyloidogenesis may be a neuropathological response in people who are severely and chronically exposed to neurotoxic air pollutants.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"89 9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521015","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 associations of joint exposure to various living environmental factors with the risk of frailty and all-cause mortality: a nationally representative cohort study","authors":"Jinqi Wang, Xiaoyu Zhao, Yanchen Zhao, Zhiyuan Wu, Xia Li, Jing Wei, Xiuhua Guo, Lixin Tao","doi":"10.1093/gerona/glaf102","DOIUrl":"https://doi.org/10.1093/gerona/glaf102","url":null,"abstract":"Background The relationships of joint exposure to various outdoor and indoor environmental factors with the risk of frailty and mortality remain unclear. Methods Based on the China Health and Retirement Longitudinal Study, we enrolled 13745 participants in the final analysis. The living environmental score incorporated seven factors: ambient fine particulate matter, residential greenness, household fuel use, indoor temperature, water sources, building types, and household cleanliness (ranged from 0 to 8). Frailty was assessed by a 40-item deficit-accumulation frailty index. Cox proportional hazards regressions were used to assess the longitudinal associations of individual and joint exposure to living environmental factors with risk of frailty and mortality. Results In this prospective study, 3389 participants developed frailty and 815 died during a 7-year follow-up. A higher living environmental score was linked to reduced risks of frailty (hazard ratio (HR): 0.872, 95% CI: 0.854-0.890) and mortality (HR: 0.893, 95% CI: 0.856-0.932). Population-attributable fraction analyses revealed that 23.5% of frailty and 17.2% of deaths could be attributed to lower living environmental scores. For single factors, solid fuel use and PM2.5 exposure had the greatest attribution to incident frailty and all-cause mortality, respectively. The effects of low living environmental score on all-cause mortality were mediated via frailty. Conclusion Multiple living environmental risk factors were separately and jointly associated with increased risks of frailty and mortality in an additive manner, emphasizing the importance of comprehensively assessing various environmental factors to promote healthy aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218879","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":"Acute NAD+ Supplementation via NMN Does Not Rescue Functional Impairment in a LPS-Induced Delirium Mouse Model","authors":"M K Kirsten Chui, Prasanna Vadhana Ashok Kumaar, Birgit Schilling, Eric Verdin, John C Newman","doi":"10.1093/gerona/glaf116","DOIUrl":"https://doi.org/10.1093/gerona/glaf116","url":null,"abstract":"Delirium is a serious neuropsychiatric condition that lacks an effective treatment intervention. A confusional state often brought on by acute illness, delirium is associated with acute inflammation and metabolic dysfunction. NAD+ is a metabolite involved in both cellular energy generation and immunomodulation, that has previously been found to promote metabolic function and reduce inflammation. Whether NAD+ supplementation may be beneficial for delirium has not been explored yet. In this study, we investigate the effect of acute supplementation of NMN, a direct precursor of NAD+, in a LPS-induced delirium mouse model. While NAD+ did not rescue the delirium-like sickness behavior and metabolic dysfunction in mice, a comprehensive cytokine profile analysis did reveal rescue of plasma IFNγ levels by NMN supplementation and partial improvement on the levels of IL-12p40, RANTES, LIX, and IL-17 which were sex dependent.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184115","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":"Baseline Plasma GDF15 and Recovery of Physical Function Following Total Knee Replacement in The Study of Physical Resilience and Aging","authors":"William A Fountain, Nicholas Milcik, Nicholas Schmedding, Karen Bandeen-Roche, Mallak K Alzahrani, Brian Buta, Meredith Dobrosielski, Jackie Langdon, Frederick Sieber, Julius K Oni, Thomas Laskow, Qian-Li Xue, Ravi Varadhan, Jeremy Walston","doi":"10.1093/gerona/glaf115","DOIUrl":"https://doi.org/10.1093/gerona/glaf115","url":null,"abstract":"Growth-differentiation factor 15 (GDF15), a cytokine with the ability to regulate metabolic and inflammatory activity, is negatively associated with physical and cognitive function, and increases in circulation with age. Mechanistically, the expression of GDF15 is stimulated by mitochondrial stress across multiple tissues. We hypothesized elevations in basal circulating GDF15 were negatively associated with physical function following surgery in older adults. This was assessed in 112 Study of Physical Resilience and Aging (SPRING) participants (age 69.6 ± 6.9 years, 66% women) undergoing total knee replacement (RESTORE). The associations between pre-operative plasma GDF15 levels and longitudinal post-operative physical resilience measures including the Short Physical Performance Battery (SPPB) and Pittsburgh Fatigability Scale (PFS) were evaluated. At baseline, higher circulating GDF15 levels were associated with older age, higher BMI, diabetes, and physical frailty (P&amp;lt;0.05). Circulating GDF15 levels were not associated with SPPB or PFS scores prior to knee replacement (P&amp;gt;0.05). Higher baseline circulating GDF15 levels were negatively associated with the recovery of SPPB scores six months following knee replacement (P&amp;lt;0.05). However, there was no significant association between baseline circulating GDF15 levels and the recovery of PFS scores within the same timeframe (P&amp;gt;0.05). There were no significant associations between baseline circulating GDF15 and recovery of SPPB or PFS scores at 1-month or 12-months follow up (P&amp;gt;0.05). These findings suggest that pre-operative circulating GDF15 levels may provide some insight into the capacity to recover physical function following total knee replacement surgery. Further investigation is necessary to elucidate relationships between GDF15 and the biology of physical resilience.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153347","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 triglyceride-glucose index as a measure of insulin resistance, mediated the relationship between air pollution and hypertension in middle-aged and older adults.","authors":"Jinglong Zhang,Jia Chen,Jing Nie,Yifan Shi,Jing Wei,Yangjin Yan,Shichao Han,Wenyuan Yu,Xiangyu Li,Zhizhou Duan,Zhiping Niu","doi":"10.1093/gerona/glaf114","DOIUrl":"https://doi.org/10.1093/gerona/glaf114","url":null,"abstract":"BACKGROUNDPrevious studies have identified links between air pollution, insulin resistance (IR), and hypertension risk, but the mediating role of IR in the relationships between air pollution exposure and hypertension remains unexplored.METHODSThis national cross-sectional study included 10,405 middle-aged and older adults from 120 Chinese cities. Long-term air pollution exposure was estimated using three-year average levels of six air pollutants (particulate matter with a diameter ≤2.5 μm (PM2.5) or ≤ 10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3)). The triglyceride-glucose (TyG) index was used to assess IR. Generalized linear models were used to examine associations between air pollution, the TyG index, and hypertension risk. Mediation effect models were employed to evaluate the mediating role of the TyG index in the relationships between air pollution and hypertension.RESULTSFor each inter-quartile range increase in PM2.5, PM10, SO2, NO2, CO, and O3, we observed corresponding increases of 0.017, 0.019, 0.020, 0.027, 0.027, 0.013 in TyG index, and the odds ratio of 1.232, 1.269, 1.297, 1.323, 1.268 and 1.080 for hypertension, respectively. Mediation effect models revealed that the TyG index contributed 9.94%, 9.83%, 10.16%, 11.41%, 14.17%, and 21.89% mediating roles in the negative impact of PM2.5, PM10, SO2, NO2, CO, and O3 on hypertension risks, respectively.CONCLUSIONAir pollution exposure is associated with increased IR and hypertension risk, with IR playing a significant mediating role. This study highlighted that IR could serve as a key biological mechanism linking air pollution to hypertension risk.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103848","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":"Mitochondrial bioenergetic profiling in T cell subsets associates with functional health in older adults: A cross-sectional analysis from the INSPIRE-T cohort.","authors":"Nabila Jabrane-Ferrat,Jérémy Raffin,Jordi Gouilly,Souad Najib,Anne-Laure Iscache,Catherine Marques,Julien Hall,Nathan Jolivet,Guillaume Combes,Nathalie Viguerie,Sébastien Dejean,Sophie Guyonnet,Yves Rolland,Cendrine Cabou,Bruno Vellas,Philipe de Souto Barreto,Laurent O Martinez,Hicham El Costa","doi":"10.1093/gerona/glaf112","DOIUrl":"https://doi.org/10.1093/gerona/glaf112","url":null,"abstract":"Aging varies across individuals, highlighting the need for better markers of functional decline. This study investigates the hypothesis that T cell energy metabolism is correlated with functional health in older adults. We used flow cytometry-based profiling to examine energy metabolism, focusing on mitochondrial OXPHOS activity (MitoDep, expressed as percentage), in peripheral CD4 and CD8 T cell subsets from 187 participants aged 70-89 years (mean age 78.7 [SD 5.3], 57.7% [n = 108] women) within the Inspire-T cohort. Associations with Fried frailty phenotype were evaluated, using logistic regression. Relationships with intrinsic capacity (IC) score were assessed using partial least square regression (PLS) and piecewise linear regression models, adjusting for age, sex and comorbidities. MitoDep was significantly lower in prefrail/frail individuals (47% of the study population) across several T cells subsets. In CD4 regulatory T cell (CD4Treg) subsets, higher MitoDep was significantly associated with reduced odds of prefrailty/frailty. Piecewise regression identified a breakpoint in memory CD4Treg MitoDep at 58.5% (95% CI, 50.7-67.5). Below this threshold, reduced MitoDep was significantly associated with lower IC (β = 0.40, p = 0.0104). This study establishes a novel link between T cell mitochondrial OXPHOS activity and functional health in older adults, offering insights for improved patient stratification and personalized lifestyle or therapeutic interventions.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103853","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}