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

{"title":"Large-Vessel Hemodynamics Are Associated with Glymphatic Dysfunction and Cognitive Impairment in Cerebral Small Vessel Disease","authors":"Dan Luo, Peng Zeng, Bang Zeng, Binglan Li, Lisha Nie, Yuling Peng, Yongmei Li, Tianyou Luo","doi":"10.1093/gerona/glaf225","DOIUrl":"https://doi.org/10.1093/gerona/glaf225","url":null,"abstract":"Background Disruption of cerebral hemodynamics may impair perivascular and glymphatic clearance, contributing to aging-related brain pathology. This study aimed to explore the interaction between large-vessel hemodynamics and glymphatic neuroimaging markers in cerebral small vessel disease (CSVD), a common age-related condition. Methods Using 4D flow MRI, we quantified flow/area pulsatility index (PIflow/PIarea) and wall shear stress (WSS) in carotid arteries and superior sagittal sinus (SSS) among 66 CSVD patients and 34 healthy controls (HCs). Free water (FW) fraction and diffusivity along the perivascular space (ALPS) were measured as glymphatic markers via diffusion-weighted imaging. Multivariate regressions and mediation analyses were conducted to assess the relationships between vascular metrics and glymphatic markers, as well as disease burden, adjusting for age, sex, white matter hyperintensity (WMH) volume, and vascular risk factors. Results CSVD patients exhibited increased arterial and venous PIs and WSS alongside elevated FW in multiple brain regions. PIarea of common carotid artery (CCA) and higher WSS of internal carotid artery (ICA)-C1 correlated with increased FW of basal ganglia (FW-BG); PIflow of SSS linked to FW in the hippocampus; and PIarea of ICA-C4 correlated with ALPS (β = 0.188-0.267, p < 0.05). Contrastingly, HCs exhibited inverse associations between PIs/WSS and glymphatic markers (β=-0.517 to -0.317, p < 0.05). Interestingly, FW-BG mediated 42.1% of the effect between PIarea-CCA and CSVD burden (BootCI:0.015-0.956, p < 0.05). Elevated WSS of SSS predicted worse global cognition (β=-0.32, p = 0.005). Conclusions Altered large-vessel hemodynamics correlated to glymphatic dysfunction and cognitive function in CSVD, highlighting the critical role of vascular health in preserving brain clearance and cognitive aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261024","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":"Joint association of serum 25-hydroxyvitamin D concentration and body mass index on the acceleration of clinical biomarker-based biological aging","authors":"Zimo Pan, Jing Zeng, Zeyu Chen, Shimin Chen, Junhan Yang, Huaihao Li, Shengshu Wang, Jianhua Wang, Nan Li, Yanping Gong, Miao Liu, Chunlin Li","doi":"10.1093/gerona/glaf215","DOIUrl":"https://doi.org/10.1093/gerona/glaf215","url":null,"abstract":"Background The possible joint association of vitamin D and obesity in regard to the clinical biomarker-based biological aging process has not been well studied. We aimed to investigate the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and body mass index (BMI) with phenotypic age (PhenoAge) and Klemera-Doubal method Biological Age (KDM-BA) acceleration. Methods This study was conducted using data from participants in the UK Biobank baseline survey. PhenoAge and KDM-BA acceleration were calculated as the residuals from regressing PhenoAge and KDM-BA on chronological age. Restricted cubic splines and multivariable logistic regression analyses were used to investigate the associations of serum 25(OH)D concentrations and BMI with PhenoAge and KDM-BA acceleration. Interaction terms were introduced to evaluate whether the combined effects of the two factors exceeded their cumulative effects. Mediation analyses were conducted to assess whether PhenoAge or KDM-BA acceleration potentially mediated the association between 25(OH)D or BMI and all-cause mortality. Results In both Analysis 1 (n = 389,217) for PhenoAge, and Analysis 2 for KDM-BA (n = 329,561), participants had similar mean ages (56.49 ± 8.12 and 56.34 ± 8.13 years), sex distributions (46.7% and 46.5% men), and predominantly White ethnicity (95.0%). Consistent relationships were found between 25(OH)D, BMI and clinical biomarker-based biological age acceleration measured by PhenoAge and KDM-BA. Participants whose serum 25(OH)D concentration ≥ 50.0 nmol/L or with normal weight (BMI < 25kg/m2) had the lowest odds of clinical biomarker-based biological age acceleration. Compared to participants with serum 25(OH)D levels ≥ 50.0 nmol/L and the normal weight, participants with both 25(OH)D < 25.0 nmol/L and BMI ≥ 30.0 kg/m2 had the highest odds of PhenoAge acceleration [OR (95% CI), 2.387 (2.303, 2.474)] and KDM-BA acceleration [OR (95% CI), 4.096 (3.926, 4.274)]. The mediation analysis revealed that PhenoAge acceleration mediated 11.4% and 47.1% of the associations of 25(OH)D and BMI with all-cause mortality, while KDM-BA acceleration accounted for 7.41% and 55.2% of these associations. Conclusions Serum 25(OH)D concentrations and BMI were significantly associated with the acceleration of biological aging. Combining vitamin D deficiency and obesity demonstrated enhanced synergistic association on the biological aging process, highlighting the importance of vitamin D and BMI in promoting healthy aging.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260662","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":"A Harmonized Frailty Index Using Global Aging Data","authors":"Benjamin Seligman, Mark Ward, Maddalena Ferranna, David E Bloom, Rose Anne Kenny, Ariela R Orkaby","doi":"10.1093/gerona/glaf217","DOIUrl":"https://doi.org/10.1093/gerona/glaf217","url":null,"abstract":"Background Frailty is a common syndrome among older adults, associated with multiple adverse health outcomes. Work harmonizing frailty measurement across 25 countries and regions and different socioeconomic environments is limited. A harmonized definition is needed to assess frailty across settings to inform comparative studies of health and health care. Methods Data on adults aged 50+ from eight health and retirement surveys were analyzed: CHARLS (China), ELSA (England and Wales), ELSI (Brazil), HRS (USA), LASI (India), MHAS (Mexico), SHARE (Europe and Israel), and TILDA (Ireland). We produced 30-item deficit accumulation frailty index (FI) from shared variables. We assessed within-survey distributions and, in four surveys with available data (HRS, MHAS, SHARE, and TILDA), association with mortality. Results 184,715 participants were included; mean (SD) age was 65.1 (9.80) and 55.1% were female. Mean (SD) FI was 0.196 (0.133), and 39.2% were frail. Frailty distributions were right-skewed, with higher median FI for females than males (p < 0.0001). Kaplan-Meier analysis showed lower survival with greater frailty in studies with survival data. Hazard ratios (95% CI, p-value) for severe frailty (FI ≥ 0.4) compared with non-frailty (FI < 0.1) after adjustment for age, gender, and smoking status were 5.50 (4.89–6.19), 4.36 (3.67–5.18), 8.81 (6.44–12.05), and 3.97 (2.99–5.27) for HRS, MHAS, SHARE, and TILDA respectively, all with p < 0.0001. Conclusions This is a harmonized FI developed using data from multiple settings, with strong associations with mortality. This is a useful tool to better understand aging in a global context.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"159 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261026","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":"Understanding Frailty Changes Surrounding Hip Fracture","authors":"Jianhong Xu, Yanxin Wang, Jonathan Ka-Long Mak, Emiel O Hoogendijk, Graciela Muniz-Terrera, Chenkai Wu","doi":"10.1093/gerona/glaf226","DOIUrl":"https://doi.org/10.1093/gerona/glaf226","url":null,"abstract":"Background Hip fractures significantly increase health risks in older adults, yet the evolution of frailty before and after fracture and its impact on mortality remain unclear. This study investigated the relationship between frailty trajectories surrounding hip fractures and subsequent mortality risk. Methods This population-based cohort study used UK Biobank data with linked hospital and mortality records through 2023, including 4,963 participants with hip fractures. Frailty was assessed via the Hospital Frailty Risk Score based on ICD-10 codes. Latent class trajectory analysis modeled frailty trends 12 months before and after fracture. Multinomial logistic regression identified frailty trajectory groups, and Cox models assessed their association with all-cause mortality. Results Among 4,963 participants (mean age: 70.1 years, 64.6% females), we identified three pre-fracture frailty trajectories: persistently robust (44.2%), moderately frail (37.1%), and progressively frail (18.7%). Frailty remained stable except in the progressively frail group, where scores increased by 28.6% in the year before fracture. Post-fracture, three trajectories emerged: moderate frailty with stability (63.0%), high frailty with stability (30.8%), and rapidly progressive frailty (6.2%). Higher pre-fracture frailty was strongly associated with greater post-fracture frailty. Mortality risk varied significantly across combined pre- and post-fracture frailty trajectories, with the highest risk in those with rapidly progressive frailty post-fracture. Conclusions Distinct frailty trajectories before and after hip fracture are associated with differential mortality risk, highlighting the need for routine frailty assessments. Identifying high-risk individuals may facilitate targeted interventions to improve recovery and survival in patients with hip fractures.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260616","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":"Machine learning prediction of survival in centenarians after age 100: A retrospective, population-based cohort study","authors":"Jonathan K L Mak, Noel C Yue, Gloria Hoi-Yee Li, Jacqueline K Yuen, Tung Wai Auyeung, Kathryn Choon Beng Tan, Ching-Lung Cheung","doi":"10.1093/gerona/glaf218","DOIUrl":"https://doi.org/10.1093/gerona/glaf218","url":null,"abstract":"Background Whether survival at extreme ages can be accurately predicted remains unclear. This study explored the feasibility of using machine learning (ML) and electronic health records (EHRs) to predict mortality in centenarians and identify key survival determinants. Methods We analyzed 9,718 centenarians (83% women) from the population-based EHR database in Hong Kong (2004–2018). Data were randomly split into 70% training and 30% testing cohorts. Using 82 predictors, including demographics, diagnoses, prescriptions, and laboratory results, we trained stepwise logistic regression and four ML algorithms to predict 1-year, 2-year, and 5-year all-cause mortality after age 100. Model performance was evaluated using discrimination (area under the receiver operating characteristic curve [AUROC]) and calibration metrics. In an independent cohort of 174,606 oldest-old adults aged 85–105 years, we further compared AUROCs of models incorporating the identified predictors versus comorbidity and frailty scores across different age groups. Results Among the ML models, eXtreme Gradient Boosting algorithm provided the best performance, with AUROCs of 0.707 (95% CI = 0.685–0.730) for 1-year mortality and 0.704 (0.686–0.723) for 2-year mortality in the testing cohort. However, all models showed poor calibration for 5-year mortality. Top 3 predictors of mortality included lower albumin levels, more frequent hospitalizations, and higher urea levels. Models including these predictors consistently outperformed comorbidity and frailty for mortality prediction among oldest-old adults. Conclusion Utilizing ML models and routinely collected EHRs can predict short-term survival in centenarians with moderate accuracy. Further research is needed to determine whether mortality predictors differ across age in the oldest-old population.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246939","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 Health Cost of Irregular Sleep Timing: Age Differences in Social Jet Lag and Health Outcomes Among Middle-Aged and Older Adults (Brief Report)","authors":"Eunjin Lee Tracy, Eunjung Kim, Naomi R Meinertz, Getrude K Nyang’au","doi":"10.1093/gerona/glaf216","DOIUrl":"https://doi.org/10.1093/gerona/glaf216","url":null,"abstract":"Background Social jet lag, a misalignment between circadian rhythms and societal schedules, has been reported to pose significant health risks. However, evidence of social jet lag's implications on health outcomes among middle-aged and older adults, and the moderating role of age on these associations is limited. We investigated the cross-sectional associations of social jet lag with key health outcomes and considered the moderating role of age. Methods This study included 661 participants aged 50-83 drawn from the 2018 wave of the U.S.-based Health and Retirement Study. We computed multiple linear regressions to estimate the associations between social jet lag—calculated from self-reported sleep timing as the difference between weekday and weekend sleep midpoints—and depressive symptoms, cognitive functioning, and body mass index. Results Unadjusted regressions indicated that higher levels of social jet lag were associated with higher depressive symptoms and higher body mass index. No association was found between social jet lag and cognitive functioning. In adjusted regressions, higher levels of social jet lag remained positively associated with higher depressive symptoms, and this association was moderated by age. Specifically, higher levels of social jet lag were linked to higher depressive symptoms only among adults over age 61.24, whereas no such association was observed in participants aged 50-61.24. Conclusion The findings suggest that greater social jet lag is associated with higher depressive symptoms, particularly among older adults. Future research should explore causal links between social jet lag and health outcomes to inform interventions aimed at improving mental health in this population.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246940","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":"Mismatch Between Echocardiography-predicted Cardiac Age and Chronologic Age: Insights from The Multi-Ethnic Study of Atherosclerosis.","authors":"Christy Zheng,Prashant Rao,Aaron Troy,Monica Mukherjee,Jordan B Strom","doi":"10.1093/gerona/glaf223","DOIUrl":"https://doi.org/10.1093/gerona/glaf223","url":null,"abstract":"","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247124","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 Between Bilirubin and Vestibular Dysfunction in U.S. in Middle-Aged and Elderly People Insights from NHANES 1999 – 2004 and Mendelian Randomization Analysis","authors":"Jing Luo, Hengkang He, Fang Zhang, Yixi Xiao, Xiong Zhang, Jingwen Zhang, Yang Tian, Jianhui Zhang","doi":"10.1093/gerona/glaf224","DOIUrl":"https://doi.org/10.1093/gerona/glaf224","url":null,"abstract":"Background Vestibular dysfunction represents a significant public health burden, and the association with the endogenous antioxidant bilirubin remains controversial. This study aimed to systematically evaluate the association and potential causal mechanisms between serum total bilirubin (STB) and vestibular dysfunction by integrating observational research with causal inference methods. Methods Cross-sectional data from NHANES (1999-2004) were analyzed using weighted multivariable logistic regression and restricted cubic splines to examine the association between serum total bilirubin (STB) quartiles and vestibular dysfunction (assessed by Romberg test failure). Bidirectional two-sample Mendelian randomization (MR) was further employed to assess causality using genetic instruments. Results Among 4,500 participants, a multivariable-adjusted model revealed a significant inverse association between moderate STB concentrations (Q2: 10.27–11.97 μmol/L) and vestibular dysfunction (OR = 0.71, P = 0.018). A nonlinear dose-response relationship was observed (P-nonlinear = 0.002). Age significantly modified the effect, with protection in participants <60 years (OR = 0.97, P = 0.006) but risk in those ≥60 (OR = 1.03, P = 0.016). Genetically elevated direct bilirubin reduced overall vestibular dysfunction risk (OR = 0.84, P < 0.001), most notably for Ménière’s disease (OR = 0.76, P = 0.007). Sensitivity analyses supported result robustness (no heterogeneity or pleiotropy detected). Conclusion Moderate STB concentrations may reduce vestibular dysfunction risk. This protective effect is causally mediated by bilirubin in individuals under 60, suggesting bilirubin homeostasis could be a novel target for prevention. The reversed association in older adults warrants further investigation.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"114 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247100","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 interface of geroscience with longitudinal health disparities research: A 20-year retrospective of the HANDLS Study","authors":"Nicole Noren Hooten, Nicolle A Mode, Shafagh Valipour, Alan B Zonderman, Michele K Evans","doi":"10.1093/gerona/glaf214","DOIUrl":"https://doi.org/10.1093/gerona/glaf214","url":null,"abstract":"Geroscience may be the juggernaut that coalesces the pathways of biologic knowledge to expand our understanding beyond describing differences in rates of aging to feasible interventions for improving quality of life as we age. To accomplish this, geroscience must interdigitate with long-standing immutable factors about health. As early as the 17th-century, physicians and early demographers like John Graunt, Percival Potts, Bernardino Ramazzini, and Rudolf Virchow identified the importance of differences in health trajectories and outcomes for individuals, and underlying aspects of health disparities. These differences in health status relate to numerous social determinants of health as they interact with biological risk factors and the environment. These populations and the psychosocial factors that influence health and longevity must be considered as an integral part of geroscience. Longitudinal studies that examine factors influencing the development of age-related health differences over time should be a key component of geroscience. The HANDLS study provides a useful demonstration project showing the value of studying aging in urban dwelling American adults, some of whom face significant social adversity based on race, socioeconomic status, and other factors.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234924","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":"Predominant role of fat mass in the association between HMB and frailty","authors":"Begoña Molina-Baena, Jose Antonio Carnicero, Suzette L Pereira, Ricardo Rueda, Ángela Santos-Fandila, Alejandro Álvarez-Bustos, Francisco José García-García, Leocadio Rodríguez-Mañas","doi":"10.1093/gerona/glaf203","DOIUrl":"https://doi.org/10.1093/gerona/glaf203","url":null,"abstract":"Background β-hydroxy-β-methylbutyrate (HMB) is a bioactive metabolite formed from breakdown of leucine, which increases muscle protein synthesis and reduces muscle breakdown. Previous studies have shown an inverse association between HMB levels and frailty in older adults. This study aims to assess if body composition influences this association. Methods A cross-sectional analysis was conducted using data from a cohort of adults ≥65 years from the Toledo Study of Healthy Aging. Body composition [total lean (TBLM) and fat mass (TBFM)] was assessed using dual-energy X-ray absorptiometry. Frailty was assessed with the Frailty Trait Scale (FTS-12). Six regression models were employed to examine HMB/body composition ratios and frailty, adjusting by age, sex, comorbidity, waist-to-hip ratio, nutritional status and Mediterranean Diet adherence. Results Data from 1257 individuals (56.72% females, mean age 74.6 ± 5.95 years) were analyzed. Significantly higher values of HMB levels were observed in men compared to women. HMB/body composition ratios were significantly associated with frailty in both sexes. Increased HMB/TBFM ratios occurred due to both higher HMB levels (Q1: 0.155 ± 0.027 ng/ml vs. Q4: 0.280 ± 0.057 ng/ml) and lower fat mass (Q1: 19.11 ± 3.12 kg/m2 vs. Q4: 11.34 ± 2.44 kg/m2), while higher HMB/TBLM ratios were primarily driven by higher HMB levels (Q1: 0.149 ± 0.023 ng/ml vs. Q4: 0.292 ± 0.05 ng/ml), while lean mass remained constant (Q1: 25.11 ± 2.79 kg/m2 vs. Q4: 24.62 ± 2.91 kg/m2). The protective effect of the HMB/TBFM ratio was independent of the lean mass ratio. Conclusion The relationship between endogenous HMB and frailty is modified by body composition, with a stronger impact mediated by fat mass than lean mass. Future studies should explore the therapeutic implications of HMB supplementation in age-related changes in body composition and frailty.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235512","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}