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

{"title":"Exercise Promotes Glutamate Transporter-Mediated Glutamate Uptake in the Striatum to Regulate MSN Plasticity and Alleviate Behavioral and Functional Impairments in PD Rats.","authors":"Ping Chen,Wen-Hui Zhou,Gang-Qiang Li,Quan Yang,Bing Liu,Xin-Yu Yi,Yuan Zeng","doi":"10.1093/gerona/glag173","DOIUrl":"https://doi.org/10.1093/gerona/glag173","url":null,"abstract":"This study investigated whether exercise ameliorates behavioral deficits in a rat model of Parkinson's disease (PD) by regulating medium spiny neuron (MSN) plasticity via striatal astrocytic excitatory amino acid transporters (EAATs). The PD model was induced by 6-hydroxydopamine (6-OHDA) and confirmed by apomorphine rotation. Exercised rats underwent 4 weeks of treadmill training. We assessed motor function using beam walking and cylinder tests. Striatal pathology was evaluated via tyrosine hydroxylase (TH) immunohistochemistry, glutamate (Glu) ELISA, c-Fos tracing, Western blotting for GLAST/GLT-1/NMDAR, Golgi staining for dendritic spines, and in vivo local field potential (LFP) recording. Compared to controls, PD rats exhibited motor impairment, dopamine depletion, increased striatal Glu levels, NMDAR expression, and beta-oscillations, alongside reduced EAAT expression and spine density. Exercise significantly reversed these abnormalities and improved behavior. Notably, pharmacological blockade of EAATs in exercised rats completely abolished these neuroprotective effects, reinstating the PD phenotype. These findings indicate that treadmill exercise upregulates striatal EAATs (GLAST/GLT-1), enhances Glu uptake, reduces extracellular Glu, and suppresses NMDAR overactivation and beta-oscillations. This restoration of Glu homeostasis promotes MSN morphological and functional remodeling, serving as a critical mechanism for exercise-induced behavioral improvement in PD.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"267 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388628","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":"Adolescent Dietary Restriction Improves Cognition and Frailty in Aged Female Wistar Rats.","authors":"Valentina Simeunovic,Aleksandra Mladenovic,Milica Prvulovic,Milena Jovic,Smilja Pracer,Srdjan Sokanovic","doi":"10.1093/gerona/glag174","DOIUrl":"https://doi.org/10.1093/gerona/glag174","url":null,"abstract":"Dietary restriction (DR) is the most studied non-pharmacological intervention for extending both lifespan and healthspan. While previously considered universally beneficial, recent findings indicate that the effects of DR depend on its onset and duration. Although frequently practiced among teenage girls, the effects of DR in this developmental period remain insufficiently investigated, and existing conclusions are scarce. This study aims to determine the short- and long-term effects of mild adolescent DR on the behavior and frailty in aging female Wistar rats. Female Wistar rats were fed ad libitum (AL) or were dietary restricted (70% of AL daily intake) during early adolescence (EADR), middle adolescence (MADR), or both early and middle adolescence (EMADR). Short-term effects were examined using the Open Field (OF) and Y-maze tests, while long-term effects were assessed using OF, Y-maze, and Novel Object Recognition (NOR) tests, along with survival rate and frailty assessments. Long-term effects on cortical synaptic markers were examined by analyzing the expression of synaptophysin (SPH), drebrin, postsynaptic density protein 95 (PSD95), and phosphorylated PSD95 (p-PSD95). Despite the absence of early behavioral effects, predominantly beneficial effects on survival, behavior, frailty, followed by changes in synaptic proteins have been noticed at old age. Our results showed onset- and duration-dependent effects of adolescent DR on aged animals. This study is the first to evaluate the lifelong effects of adolescent DR and highlights the importance of early nutritional habits and the need for caution in dietary interventions during critical developmental stages.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"136 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148380008","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":"Longitudinal changes in radiomic features of skeletal muscle on CT images with changes in muscle strength and physical performance in older adults.","authors":"Megan Hetherington-Rauth,Tyler A Mansfield,Ashley A Weaver,Leon Lenchik,Peggy M Cawthon","doi":"10.1093/gerona/glag172","DOIUrl":"https://doi.org/10.1093/gerona/glag172","url":null,"abstract":"BACKGROUNDSkeletal muscle health is a key determinant of aging, independence, and disease outcomes. Traditional computed tomography (CT)-derived measures of muscle cross-sectional area (CSA) and density reflect muscle quantity and quality but may not capture structural heterogeneity relevant to functional decline. Radiomics, a CT image analysis approach, enables extraction of high-dimensional texture features, offering additional insight into muscle quality. While muscle radiomics have been associated with strength and mobility in older adults, longitudinal applications remain understudied. We examined whether 5-year changes in thigh muscle radiomic features were associated with changes in muscle strength and performance in the Health, Aging, and Body Composition Study.METHODSThigh CT scans from 1321 older adults were analyzed using automated muscle segmentation to quantify CSA, density, and extract radiomic features. Strength measures included grip strength and maximal isokinetic knee extension; performance measures included 20-m walking speed, 5-time chair stands, and a modified performance score. Factor analysis reduced radiomic features to seven latent factors. Nested linear mixed-effects models tested associations of muscle CSA and density with outcomes, with and without radiomic factors.RESULTSFactors 2 and 5 were consistently associated with 5-year changes across muscle outcomes. Factor 2 (high pixel gray-level intensity and uniformity) was positively associated, whereas Factor 5 (pixel clustering asymmetry and heterogeneity) was inversely associated. Adding radiomic factors modestly improved model fit (p < 0.05), explaining 1-2% additional variation in performance.CONCLUSIONLongitudinal changes in thigh muscle radiomics capture subtle compositional characteristics beyond muscle CSA or density, enhancing understanding of functional decline with aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148372576","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 Contribution of Social and Economic Factors to Accelerated Biological Aging Differences Between Non-Hispanic Black and White Adults in the Health and Retirement Study.","authors":"Ashraf Abugroun,Torsten B Neilands,Jennifer Livaudais-Toman,Julene K Johnson,Leah Karliner,Margaret C Fang","doi":"10.1093/gerona/glag169","DOIUrl":"https://doi.org/10.1093/gerona/glag169","url":null,"abstract":"BACKGROUNDBiological aging predicts health outcomes beyond chronological age. The relative contribution of social, economic, and health factors to biological aging differences between Black and White adults remains unclear.METHODSIn a cross-sectional analysis of 2,086 community-dwelling adults aged ≥60 years from the 2016 Health and Retirement Study (1,757 non-Hispanic White; 329 non-Hispanic Black), biological age was measured using DNA methylation-based GrimAge. Accelerated aging was defined as having a biological age older than expected for one's chronological age. We used logistic regression to assess the impact of race on accelerated aging and decomposition analysis to determine factors explaining differences in accelerated aging between Black and White participants. Covariate blocks were: age, education, wealth, social frailty assessed using a composite index measuring social connections, financial autonomy, neighborhood environment, volunteering and employment engagement, behavioral factors (physical activity, alcohol use, sleep disorder, body mass index); medical conditions; and physical disability.RESULTSBlack participants had higher accelerated aging than White participants (57.1% vs 41.8%; standardized mean difference, 0.3). In the staged decomposition of the biological aging gap, age and education explained 21.1% of the difference. The cumulative explained share rose to 51.8% with wealth, 77.6% with social frailty, 80.3% with health behaviors, 90.5% with medical conditions, and 91.6% with physical disability. In multivariable logistic regression adjusting for all domains, the racial difference was no longer significant.CONCLUSIONSSocial and economic factors largely explained accelerated biological aging differences between non-Hispanic Black and White adults. These findings identify policy-relevant targets to improve healthy aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"268 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148372531","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 frailty with age and lifespan in mice differs by strain and sex.","authors":"Dantong Zhu,Cara L Green,Sarah J Mitchell,Michael R Macarthur,Elise S Bisset,John Mach,Judy Z Wu,Brady A Samuelson,Anastasia Shindyapina,Alibek Moldakozhayev,Albina Tskhay,Alexander Tyshkovskiy,Vadim N Gladyshev,David A Sinclair,Susan E Howlett,Sarah N Hilmer,Dudley W Lamming,Alice E Kane","doi":"10.1093/gerona/glag167","DOIUrl":"https://doi.org/10.1093/gerona/glag167","url":null,"abstract":"Frailty indices have been assessed in mouse models for more than a decade, but the effect of sex and strain on frailty outcomes remains poorly understood. Here, we collated and harmonized item-level 31-item clinical frailty index (FI) and lifespan data from 17 independent cohorts, including 1,564 naturally aging mice (690 females, 874 males) across five commonly used mouse strains or substrains: C57BL/6JNIA, C57BL/6N, C57BL/6J, UM-HET3, and Diversity Outbred. A total of 3,665 observations were included across cross-sectional and longitudinal studies, some previously published, with 2,192 observations linked to known age at death. Across all cohorts, FI increased significantly with chronological age, but the rate of frailty accumulation differed by strain. Sex differences in age-associated frailty trajectories were evident only in C57BL/6JNIA mice. Significant strain- and sex-specific differences in both survival and healthspan were observed, with males generally outliving females, although sex effects varied by strain. FI was strongly associated with lifespan independent of age, although age-dependent effects emerged in specific strains with notable sex-specific patterns. At the level of individual frailty items, most health deficits showed strain-dependent associations with age and lifespan. Collectively, these findings demonstrate that the relationships between frailty, chronological age, and lifespan are strongly modulated by strain and sex. This work highlights the importance of accounting for strain and sex as factors when investigating and utilizing frailty in preclinical models.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335761","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 between Hearing Loss, Physical Activity, and Sedentary Behavior: A Nationally Representative Cross-Sectional Study in Chile.","authors":"Camilo Morales,Pablo Martinez-Amezcua,Francisco Félix Caballero,Maria J Oliveros,Pamela Seron,Esther Lopez-Garcia,Humberto Yévenes-Briones","doi":"10.1093/gerona/glag168","DOIUrl":"https://doi.org/10.1093/gerona/glag168","url":null,"abstract":"BACKGROUNDHearing loss is common in midlife and older adults and may constrain communication and participation, potentially shaping physical activity and sedentary time; however, population-based evidence remains inconsistent.METHODSWe analyzed a nationally representative sample of Chilean adults aged ≥40 years from the 2016-2017 Chile National Health Survey (n = 3512). Hearing loss was defined by a \"no\" response to any of three self-report items. Global Physical Activity Questionnaire outcomes included overall physical activity (high/moderate/low), domain-specific energy expenditure (work, transport, leisure; MET-hours/week), and high sedentary behavior (≥8 h/day). We fitted survey-weighted ordinal, gamma (log link), and logistic regression models; effect modification by sex, age, and sleep quality was tested. Sensitivity analyses used inverse probability-of-exposure weighting with gradient-boosted propensity scores.RESULTSThe weighted prevalence of hearing loss was 27.9%. Hearing loss was not associated with overall physical activity level (OR, 1.14; 95% CI, 0.90; 1.39) or with domain-specific energy expenditure at work (RR, 0.90; 95% CI, 0.75; 1.08), transport (RR, 1.02; 95% CI, 0.83; 1.25), or leisure (RR, 1.10; 95% CI, 0.86; 1.42). In contrast, hearing loss was associated with high sedentary behavior (OR, 1.81; 95% CI, 1.16; 2.82), with similar estimates after weighting (OR, 1.86; 95% CI, 1.18; 2.94). Subgroup analyses showed no consistent heterogeneity by sex, age, or sleep quality.CONCLUSIONIn Chilean adults aged ≥40 years, self-reported hearing loss was associated with prolonged sedentary time but not with overall or domain-specific physical activity. These findings support integrating hearing care with strategies to reduce sedentary behavior.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335768","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":"Challenge-based ex vivo immune profiling reveals stimulus-dependent peripheral immune reprogramming in Alzheimer's disease.","authors":"Carlos Andrés Naranjo-Galvis,Jovanny Zabaleta,Ney Alliey-Rodriguez,Luisa Matilde Salamanca-Duque","doi":"10.1093/gerona/glag166","DOIUrl":"https://doi.org/10.1093/gerona/glag166","url":null,"abstract":"Altered immune function is increasingly recognized as a contributor to Alzheimer's disease (AD); however, it remains unclear whether peripheral immune alterations reflect constitutive inflammation or stimulus-dependent changes in immune responsiveness. Addressing this distinction is critical for understanding immune dysregulation in neurodegenerative diseases. In this study, we applied a challenge-based ex vivo immune profiling approach to characterize functional immune responsiveness in patients with AD and in cognitively healthy older adults. Peripheral blood mononuclear cells were exposed to defined innate, antigenic, and mitogenic stimuli, and cytokine and β-amyloid responses were quantified in culture supernatants. Diagnosis-by-stimulus interaction effects were assessed using generalized estimating equation models, adjusted for age and sex. In parallel, exploratory correlation-based immune-amyloid network analyses and hypothesis-driven immunogenetic stratification were performed to investigate biomarker coordination patterns and context-dependent genetic influence. Baseline cytokine concentrations showed limited between-group differences, whereas ex vivo immune challenge revealed selective stimulus-dependent alterations in cytokine production. In contrast, immune stimulation revealed selective amplification of stimulus-evoked responses in AD, particularly involving IFN-γ, IL-4, and IL-10, whereas classical proinflammatory cytokines retained preserved inducibility. Exploratory genotype-stratified analyses suggested potential context-dependent differences in functional immune and β-amyloid responses to immune challenges. Together, these findings indicate that peripheral immune dysregulation in AD is characterized by stimulus-dependent differences in cytokine production that become apparent under immune challenge conditions, highlighting the value of ex vivo immune stimulation assays in translational immunology in neurodegenerative diseases.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148322792","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":"State Racism Index and physical function: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.","authors":"Hugo G Quezada-Pinedo,Tyson Brown,Ene M Enogela,Emily B Levitan,Oluwasegun P Akinyelure,Valerie A Smith,Laura C Pinheiro,Monika M Safford,Ro-Jay Reid,Tomi F Akinyemiju,C Barrett Bowling","doi":"10.1093/gerona/glag142","DOIUrl":"https://doi.org/10.1093/gerona/glag142","url":null,"abstract":"BACKGROUNDStructural racism contributes to health inequities in the U.S. This study aimed to quantify the association between State Racism Index (SRI) and physical function.METHODSIn a national U.S. community-based cohort study, 13,661 Non-Hispanic Black and White adults who had baseline information (2003-2007), SRI data (2006-2010) and physical function data (2013-2016) were included. Physical function measurements included activities of daily living (ADL), instrumental ADL (IADL), timed walk, and chair stand test. Multivariable generalized regression models (GLM) and linear regression models were used to evaluate the association between SRI and physical function. Interactions with age, sex and region were evaluated.RESULTSAmong Black participants, each unit increase in SRI was significantly associated with 2% higher IADL scores (Ratio of means [95%CI]: 1.018 (1.007, 1.029)) indicating worse function. This association attenuated after adjustment for socioeconomic factors but was stronger in the U.S. Stroke Belt region (p for interaction < 0.05). Among White participants, higher SRI was significantly associated with 2% ADL and 1% IADL lower scores (Ratio of means [95%CI]: 0.983 (0.969, 0.997) and 0.985 (0.977, 0.994), respectively) indicating better function. This association was independent of socioeconomic and health-related factors. We did not observe an association between SRI and timed walk or chair stands overall or by race.CONCLUSIONHigher state-level structural racism was associated with worse physical function among Black participants and better physical function for White participants. Associations were influenced by socioeconomic factors and magnified in southern U.S. states.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"134 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148305125","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":"Older Adults and Extreme Weather Events: Recommendations from the Research Centers Collaborative Network Workshop.","authors":"Eun Young Choi,Lingzhi Chu,Alexandra B Holland,Arun Balachandran,Sara C Zapico,Sadaf Arefi Milani,Roger Wong,Tina E Brinkley,Stephen B Kritchevsky","doi":"10.1093/gerona/glag164","DOIUrl":"https://doi.org/10.1093/gerona/glag164","url":null,"abstract":"Extreme weather events are increasingly recognized as critical determinants of health and well-being in later life. To identify priorities for advancing research at the intersection of these events and aging, the Research Centers Collaborative Network convened a 1.5-day interdisciplinary workshop. This article synthesizes discussions across three domains: the effects of weather-related hazards on aging and health outcomes; vulnerabilities and resilience of older adults; and interventions to mitigate risk. Key priorities include longitudinal studies capturing cumulative exposures and long-term outcomes across the life course, greater attention to heterogeneity within older populations, and designing interventions responsive to social and environmental contexts.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"258 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148305129","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":"Personalizing cancer care for older adults.","authors":"Jingran Ji,Mina S Sedrak","doi":"10.1093/gerona/glag126","DOIUrl":"https://doi.org/10.1093/gerona/glag126","url":null,"abstract":"","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"236 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148290351","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}