Pub Date : 2025-12-19DOI: 10.1016/j.exger.2025.113008
Yaru Zhou , Wenhua Yu , Xiaohong Liu
Backgrounds
Preserving intrinsic capacity (IC) is essential for healthy aging. This study examined the associations between longitudinal changes in IC and subsequent adverse health outcomes.
Methods
Participants were community-dwelling adults aged ≥60 years from the China Health and Retirement Longitudinal Study (CHARLS). Changes in IC between 2011 and 2013 were classified as consistently well, improved, worsened, or consistently declined. Logistic regression assessed associations with falls and hospitalization (2015), and Cox models evaluated all-cause mortality (2020).
Results
Changes in IC were significant predictors of adverse outcomes. Worsened (OR = 1.674, 95 % CI: 1.163–2.411, P = 0.006) and consistently declined changes in IC (OR = 1.914, 95 % CI: 1.373–2.668, P < 0.001) were both associated with an increased risk of falls, while domain-specific changes, such as worsened locomotion, consistently declined in cognition and fluctuations in psychology or vision, were also linked to increased fall risk (all P < 0.017). Both consistently declined IC (OR = 1.513, 95 % CI: 1.079–2.122, P < 0.017) and worsened locomotion were independent predictors of hospitalization (OR = 1.837, 95 % CI: 1.265–2.670, P = 0.001). Declines in locomotion were also strongly associated with mortality, with higher risk observed in the worsened group (HR = 1.571, 95 % CI: 1.088–2.267, P < 0.017).
Conclusions
Monitoring intrinsic capacity changes, especially locomotion decline, enables early identification of vulnerable older adults and supports timely, targeted interventions to reduce adverse outcomes.
{"title":"The correlation between changes in intrinsic capacity of older adults in Chinese communities and adverse health-related outcomes: A prospective longitudinal Cohort study","authors":"Yaru Zhou , Wenhua Yu , Xiaohong Liu","doi":"10.1016/j.exger.2025.113008","DOIUrl":"10.1016/j.exger.2025.113008","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Preserving intrinsic capacity (IC) is essential for healthy aging. This study examined the associations between longitudinal changes in IC and subsequent adverse health outcomes.</div></div><div><h3>Methods</h3><div>Participants were community-dwelling adults aged ≥60 years from the China Health and Retirement Longitudinal Study (CHARLS). Changes in IC between 2011 and 2013 were classified as consistently well, improved, worsened, or consistently declined. Logistic regression assessed associations with falls and hospitalization (2015), and Cox models evaluated all-cause mortality (2020).</div></div><div><h3>Results</h3><div>Changes in IC were significant predictors of adverse outcomes. Worsened (OR = 1.674, 95 % CI: 1.163–2.411, <em>P</em> = 0.006) and consistently declined changes in IC (OR = 1.914, 95 % CI: 1.373–2.668, <em>P</em> < 0.001) were both associated with an increased risk of falls, while domain-specific changes, such as worsened locomotion, consistently declined in cognition and fluctuations in psychology or vision, were also linked to increased fall risk (all <em>P</em> < 0.017). Both consistently declined IC (OR = 1.513, 95 % CI: 1.079–2.122, P < 0.017) and worsened locomotion were independent predictors of hospitalization (OR = 1.837, 95 % CI: 1.265–2.670, <em>P</em> = 0.001). Declines in locomotion were also strongly associated with mortality, with higher risk observed in the worsened group (HR = 1.571, 95 % CI: 1.088–2.267, <em>P</em> < 0.017).</div></div><div><h3>Conclusions</h3><div>Monitoring intrinsic capacity changes, especially locomotion decline, enables early identification of vulnerable older adults and supports timely, targeted interventions to reduce adverse outcomes.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113008"},"PeriodicalIF":4.3,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807027","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}
Pub Date : 2025-12-18DOI: 10.1016/j.exger.2025.113006
Yuwei Qi , Natasja M. van Schoor , Laura A. Schaap , Emiel O. Hoogendijk
Introduction
It has been suggested that two prominent frameworks in geriatrics, frailty and intrinsic capacity (IC), represent two opposite ends of the same continuum. Frailty quantifies accumulated deficits and vulnerability, and IC measures an individual's capacities and functional reserves. This study investigates the overlap between frailty and IC in a large cohort of older adults.
Methods
We analysed 3246 participants aged 55+ from the Longitudinal Aging Study Amsterdam. Participants were categorised into four groups: neither frail nor low IC, low IC only, frail only, and both frail and low IC. Overlap was examined across age groups. Domain scores (vitality, sensory, cognition, psychology, locomotion) were compared between groups.
Results
Among 57–59 year olds, only 2.2 % were both frail and had low IC. This proportion increased with age, reaching 53.6 % at ages 87–89, while the “frail only” and “low IC only” groups declined. Overlap between frailty and domain scores showed that the “Neither” group consistently had the highest IC scores across all five domains, while the “Both” group consistently had the lowest scores.
Conclusions
In later life, being frail does not necessarily imply low IC, and vice versa. Frailty and low IC identify different groups in early older age, but the overlap between them becomes more pronounced with increasing age. Comprehensive assessment of ageing therefore requires measures that capture both vulnerability to decline and capacity.
{"title":"Disentangling the overlap between frailty and intrinsic capacity in older adults","authors":"Yuwei Qi , Natasja M. van Schoor , Laura A. Schaap , Emiel O. Hoogendijk","doi":"10.1016/j.exger.2025.113006","DOIUrl":"10.1016/j.exger.2025.113006","url":null,"abstract":"<div><h3>Introduction</h3><div>It has been suggested that two prominent frameworks in geriatrics, frailty and intrinsic capacity (IC), represent two opposite ends of the same continuum. Frailty quantifies accumulated deficits and vulnerability, and IC measures an individual's capacities and functional reserves. This study investigates the overlap between frailty and IC in a large cohort of older adults.</div></div><div><h3>Methods</h3><div>We analysed 3246 participants aged 55+ from the Longitudinal Aging Study Amsterdam. Participants were categorised into four groups: neither frail nor low IC, low IC only, frail only, and both frail and low IC. Overlap was examined across age groups. Domain scores (vitality, sensory, cognition, psychology, locomotion) were compared between groups.</div></div><div><h3>Results</h3><div>Among 57–59 year olds, only 2.2 % were both frail and had low IC. This proportion increased with age, reaching 53.6 % at ages 87–89, while the “frail only” and “low IC only” groups declined. Overlap between frailty and domain scores showed that the “Neither” group consistently had the highest IC scores across all five domains, while the “Both” group consistently had the lowest scores.</div></div><div><h3>Conclusions</h3><div>In later life, being frail does not necessarily imply low IC, and vice versa. Frailty and low IC identify different groups in early older age, but the overlap between them becomes more pronounced with increasing age. Comprehensive assessment of ageing therefore requires measures that capture both vulnerability to decline and capacity.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 113006"},"PeriodicalIF":4.3,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790653","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}
Pub Date : 2025-12-17DOI: 10.1016/j.exger.2025.113003
Yan Chen , Tianchong Huang , Jiayin Wang , Changsheng Guo , Jing Gao , Xiaodong Feng
Background
Insulin resistance (IR) and inflammation are two crucial risk factors of sarcopenia. C-reactive protein-triglyceride glucose index (CTI) has been proposed to be a novel biomarker reflecting IR and inflammation. However, association between CTI and sarcopenia risk remains unclear.
Aim
To explore the association between CTI and sarcopenia risk.
Methods
Data were obtained from Nutrition Examination Survey (NHANES) 2001–2010 and China Health and Retirement Longitudinal Study (CHARLS) 2011–2015. NHANES was used for cross-sectional analysis, and weighted logistic regression analysis was conducted to explore association between CTI and sarcopenia. CHARLS was used for longitudinal analysis, and the primary endpoint was the first occurrence of sarcopenia over follow-up. Logistic regression analysis and Cox proportional hazard analysis were conducted to explore the relationship between CTI and the risk of sarcopenia. Restricted cubic spline (RCS) analysis was performed to investigate the non-linear association between CTI and sarcopenia risk, and receiver operating characteristics (ROC) curves and the area under the ROC curve (AUC) were utilized to assess the predictive capability of CTI on the risk of sarcopenia.
Results
A total of 11,286 Americans and 1478 Chinese aged ≥60 years were included in this study. Logistic and Cox regression analysis revealed the cross-sectional (OR: 1.52, 95 %CI: 1.15–1.99, P = 0.004) and longitudinal (HR: 1.35, 95 %CI: 1.10–1.65, P = 0.004) correlation between CTI and sarcopenia risk after adjusting the covariates. For the two databases, non-linear association between CTI and sarcopenia risk was observed (P for non-linear <0.001). Additionally, compared to CRP and the TyG index, CTI exhibited the best predictive capability for sarcopenia risk, with the highest AUC (CHARLS: 0.730, NHANES: 0.722).
Conclusion
There exist both the cross-sectional and longitudinal association between CTI level and sarcopenia risk in older adults, and it is crucial to monitor CTI in the prevention and treatment of sarcopenia.
{"title":"Association between C-reactive protein-triglyceride glucose index and risk of sarcopenia in older adults: findings from CHARLS and NHANES","authors":"Yan Chen , Tianchong Huang , Jiayin Wang , Changsheng Guo , Jing Gao , Xiaodong Feng","doi":"10.1016/j.exger.2025.113003","DOIUrl":"10.1016/j.exger.2025.113003","url":null,"abstract":"<div><h3>Background</h3><div>Insulin resistance (IR) and inflammation are two crucial risk factors of sarcopenia. C-reactive protein-triglyceride glucose index (CTI) has been proposed to be a novel biomarker reflecting IR and inflammation. However, association between CTI and sarcopenia risk remains unclear.</div></div><div><h3>Aim</h3><div>To explore the association between CTI and sarcopenia risk.</div></div><div><h3>Methods</h3><div>Data were obtained from Nutrition Examination Survey (NHANES) 2001–2010 and China Health and Retirement Longitudinal Study (CHARLS) 2011–2015. NHANES was used for cross-sectional analysis, and weighted logistic regression analysis was conducted to explore association between CTI and sarcopenia. CHARLS was used for longitudinal analysis, and the primary endpoint was the first occurrence of sarcopenia over follow-up. Logistic regression analysis and Cox proportional hazard analysis were conducted to explore the relationship between CTI and the risk of sarcopenia. Restricted cubic spline (RCS) analysis was performed to investigate the non-linear association between CTI and sarcopenia risk, and receiver operating characteristics (ROC) curves and the area under the ROC curve (AUC) were utilized to assess the predictive capability of CTI on the risk of sarcopenia.</div></div><div><h3>Results</h3><div>A total of 11,286 Americans and 1478 Chinese aged ≥60 years were included in this study. Logistic and Cox regression analysis revealed the cross-sectional (OR: 1.52, 95 %CI: 1.15–1.99, <em>P</em> = 0.004) and longitudinal (HR: 1.35, 95 %CI: 1.10–1.65, P = 0.004) correlation between CTI and sarcopenia risk after adjusting the covariates. For the two databases, non-linear association between CTI and sarcopenia risk was observed (P for non-linear <0.001). Additionally, compared to CRP and the TyG index, CTI exhibited the best predictive capability for sarcopenia risk, with the highest AUC (CHARLS: 0.730, NHANES: 0.722).</div></div><div><h3>Conclusion</h3><div>There exist both the cross-sectional and longitudinal association between CTI level and sarcopenia risk in older adults, and it is crucial to monitor CTI in the prevention and treatment of sarcopenia.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 113003"},"PeriodicalIF":4.3,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790605","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}
Musculoskeletal pain (MSP) is prevalent among middle-aged and older adults and may increase fall risk through functional decline, but evidence on pain persistence and the potential role of frailty in China remains limited.
Methods
This study utilized data from the 2011 and 2015 China Health and Retirement Longitudinal Study (CHARLS), involving 13,057 participants in 2011 and a cohort of 7390 who reported no falls in 2011 and completed the 2015 follow-up. Among them, 1046 had persistent MSP identified using standardized CHARLS pain items. Participants indicated body pain locations, with MSP noted if pain was present anywhere. Baseline MSP was recorded in 2011, and persistent MSP was reported in both 2011 and 2015. Falls were self-reported. Survey-weighted logistic regression analyzed associations, while mediation analyses used baseline MSP (2011) as exposure and frailty in 2015 as a mediator, employing a counterfactual framework to decompose effects, interpreted cautiously due to standard assumptions and a two-year fall recall window. Baseline characteristics were compared between included and excluded participants to evaluate potential selection bias.
Results
In the longitudinal cohort, 1072 incident falls were recorded, with a higher fall rate among participants with persistent MSP than among those without (25.69 % vs 12.48 %). Adjusted models showed baseline MSP increased fall risk (OR 1.36, 95 % CI 1.15–1.60), with a stronger link for persistent MSP (OR 2.08, 95 % CI 1.70–2.54). Similar trends were observed for multisite pain. Mediation analysis indicated frailty partially mediated the effect of baseline MSP on falls, accounting for about 29 % of the effect, though results were interpreted cautiously due to the two-year fall recall period.
Conclusions
In middle-aged and older Chinese adults, MSP increases fall risk, particularly with ongoing pain. Frailty might partly explain this risk, indicating the importance of combining pain management with anti-frailty measures for fall prevention.
背景：肌肉骨骼疼痛（MSP）在中老年人中普遍存在，并可能通过功能下降增加跌倒风险，但在中国，关于疼痛持续性和虚弱的潜在作用的证据仍然有限。方法：本研究利用了2011年和2015年中国健康与退休纵向研究（CHARLS）的数据，该研究涉及2011年的13057名参与者和7390名2011年未报告跌倒并完成2015年随访的队列。其中1046例使用标准化CHARLS疼痛项目确诊为持续性MSP。参与者指出身体疼痛的位置，MSP记录疼痛是否存在于任何地方。基线MSP记录于2011年，持续MSP报告于2011年和2015年。跌倒是自我报告的。调查加权逻辑回归分析了关联，而中介分析使用基线MSP（2011年）作为暴露，2015年脆弱性作为中介，采用反事实框架分解效应，由于标准假设和两年的秋季回忆窗口，解释谨慎。比较纳入和未纳入受试者的基线特征，以评估潜在的选择偏倚。结果在纵向队列中，记录了1072例跌倒事件，持续性MSP参与者的跌倒率高于非持续性MSP参与者（25.69% vs 12.48%）。调整后的模型显示，基线MSP增加跌倒风险（OR 1.36, 95% CI 1.15-1.60），与持续性MSP有更强的联系（OR 2.08, 95% CI 1.70-2.54）。多部位疼痛也有类似的趋势。中介分析表明，虚弱部分介导了基线MSP对跌倒的影响，约占29%的影响，尽管由于两年的跌倒回忆期，结果被谨慎地解释。结论：在中国中老年成年人中，MSP增加跌倒风险，特别是持续疼痛。虚弱可能部分解释了这种风险，表明将疼痛管理与抗虚弱措施结合起来预防跌倒的重要性。
{"title":"Persistent musculoskeletal pain and subsequent falls in China: Evidence from CHARLS with exploratory frailty mediation analyses","authors":"Ruizheng Zhu , Guangjun Tang , Manhong Yang , Junde Wu , Zhaojun Chen","doi":"10.1016/j.exger.2025.113005","DOIUrl":"10.1016/j.exger.2025.113005","url":null,"abstract":"<div><h3>Background</h3><div>Musculoskeletal pain (MSP) is prevalent among middle-aged and older adults and may increase fall risk through functional decline, but evidence on pain persistence and the potential role of frailty in China remains limited.</div></div><div><h3>Methods</h3><div>This study utilized data from the 2011 and 2015 China Health and Retirement Longitudinal Study (CHARLS), involving 13,057 participants in 2011 and a cohort of 7390 who reported no falls in 2011 and completed the 2015 follow-up. Among them, 1046 had persistent MSP identified using standardized CHARLS pain items. Participants indicated body pain locations, with MSP noted if pain was present anywhere. Baseline MSP was recorded in 2011, and persistent MSP was reported in both 2011 and 2015. Falls were self-reported. Survey-weighted logistic regression analyzed associations, while mediation analyses used baseline MSP (2011) as exposure and frailty in 2015 as a mediator, employing a counterfactual framework to decompose effects, interpreted cautiously due to standard assumptions and a two-year fall recall window. Baseline characteristics were compared between included and excluded participants to evaluate potential selection bias.</div></div><div><h3>Results</h3><div>In the longitudinal cohort, 1072 incident falls were recorded, with a higher fall rate among participants with persistent MSP than among those without (25.69 % vs 12.48 %). Adjusted models showed baseline MSP increased fall risk (OR 1.36, 95 % CI 1.15–1.60), with a stronger link for persistent MSP (OR 2.08, 95 % CI 1.70–2.54). Similar trends were observed for multisite pain. Mediation analysis indicated frailty partially mediated the effect of baseline MSP on falls, accounting for about 29 % of the effect, though results were interpreted cautiously due to the two-year fall recall period.</div></div><div><h3>Conclusions</h3><div>In middle-aged and older Chinese adults, MSP increases fall risk, particularly with ongoing pain. Frailty might partly explain this risk, indicating the importance of combining pain management with anti-frailty measures for fall prevention.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 113005"},"PeriodicalIF":4.3,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790652","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}
Pub Date : 2025-12-16DOI: 10.1016/j.exger.2025.112998
Ming-Jun Hu , Xiao-Min Dong , Xue-Li Wang, Bei Yao, Fu Yu, Dan Su, Lu Li, Yong-Liang Zhang, Xin-Min Chu
Objective
Chronotype represents individual's circadian preference in behavioral and circadian rhythm. This study aimed to investigate association between chronotype and nonalcoholic fatty liver disease (NAFLD) and underlying metabolic mechanisms in middle-aged and older adults.
Methods
This cross-sectional study included 744 general middle-aged and older adults. Chronotype was assessed using the Morningness-Eveningness Questionnaire. Untargeted metabolomic profiling was identified using liquid chromatography with high-resolution mass spectrometry. Logistic regression model was used to evaluate association between chronotype and NAFLD. A metabolome-wide association study coupled with mediation analysis was conducted to assess metabolic dysregulation related with chronotype and NAFLD.
Results
Chronotype was categorized as morning in 33.1 % of participants, intermediate in 46.8 %, and evening in 20.1 %. After adjustment for covariates, evening chronotype was significantly associated with higher NAFLD risk (OR = 1.70, 95 % CI: 1.03, 2.81) compared to morning chronotype. We identified 81 metabolite features that were significantly associated with chronotype. The comparison between NAFLD and non-NAFLD revealed 251 metabolic differences, implicating 5 metabolic pathways: Arginine biosynthesis, Histidine metabolism, Alanine, aspartate and glutamate metabolism, Arginine and proline metabolism, and beta-Alanine metabolism. Mediation analyses suggested that 7 metabolites (such as Asparaginyl-Proline and DG(11D3/11D5/0:0)) might be potential mediators in association of chronotype with NAFLD, with mediated proportions ranging from 12.1 % to 20.6 %.
Conclusion
Evening chronotype was associated with increased risk of NAFLD in middle-aged and older adults. Chronotype-related metabolomic alterations, including Asparaginyl-Proline and some lipid metabolites, might represent an associative pathway between chronotype and NAFLD. This highlighted the importance of maintaining circadian rhythms for metabolic health.
{"title":"Chronotype, serum metabolome, and nonalcoholic fatty liver disease in middle-aged and older adults: Association and potential mediation analyses","authors":"Ming-Jun Hu , Xiao-Min Dong , Xue-Li Wang, Bei Yao, Fu Yu, Dan Su, Lu Li, Yong-Liang Zhang, Xin-Min Chu","doi":"10.1016/j.exger.2025.112998","DOIUrl":"10.1016/j.exger.2025.112998","url":null,"abstract":"<div><h3>Objective</h3><div>Chronotype represents individual's circadian preference in behavioral and circadian rhythm. This study aimed to investigate association between chronotype and nonalcoholic fatty liver disease (NAFLD) and underlying metabolic mechanisms in middle-aged and older adults.</div></div><div><h3>Methods</h3><div>This cross-sectional study included 744 general middle-aged and older adults. Chronotype was assessed using the Morningness-Eveningness Questionnaire. Untargeted metabolomic profiling was identified using liquid chromatography with high-resolution mass spectrometry. Logistic regression model was used to evaluate association between chronotype and NAFLD. A metabolome-wide association study coupled with mediation analysis was conducted to assess metabolic dysregulation related with chronotype and NAFLD.</div></div><div><h3>Results</h3><div>Chronotype was categorized as morning in 33.1 % of participants, intermediate in 46.8 %, and evening in 20.1 %. After adjustment for covariates, evening chronotype was significantly associated with higher NAFLD risk (OR = 1.70, 95 % CI: 1.03, 2.81) compared to morning chronotype. We identified 81 metabolite features that were significantly associated with chronotype. The comparison between NAFLD and non-NAFLD revealed 251 metabolic differences, implicating 5 metabolic pathways: Arginine biosynthesis, Histidine metabolism, Alanine, aspartate and glutamate metabolism, Arginine and proline metabolism, and beta-Alanine metabolism. Mediation analyses suggested that 7 metabolites (such as Asparaginyl-Proline and DG(11D3/11D5/0:0)) might be potential mediators in association of chronotype with NAFLD, with mediated proportions ranging from 12.1 % to 20.6 %.</div></div><div><h3>Conclusion</h3><div>Evening chronotype was associated with increased risk of NAFLD in middle-aged and older adults. Chronotype-related metabolomic alterations, including Asparaginyl-Proline and some lipid metabolites, might represent an associative pathway between chronotype and NAFLD. This highlighted the importance of maintaining circadian rhythms for metabolic health.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 112998"},"PeriodicalIF":4.3,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784103","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}
Pub Date : 2025-12-16DOI: 10.1016/j.exger.2025.112996
Guilherme da Silva Rodrigues , Natalia Yumi Noronha , Andressa Crystine da Silva Sobrinho , Bernadette Jones-Freeman , Robin Grolaux , Camila Fernanda Cunha Brandao , Julio Sergio Marchini , Lígia Moriguchi Watanabe , Carla Barbosa Nonino , Andrew Teschendorff , Nir Eynon , Carlos Roberto Bueno Júnior , Macsue Jacques
Introduction
Menopause is associated with immunosenescence and altered immune profiles, potentially reducing immune competence. Physical exercise may counteract these changes by modulating DNA methylation in fitness-related genes.
Methods
This observational bioinformatics study analyzed genome-wide DNA methylation profiles derived from whole blood using two publicly available datasets from Brazilian cohorts (Illumina MethylationEPIC 850K). The analysis included pre- (PreM, n = 13; 34 ± 4.7 years) and postmenopausal (PostM, n = 49; 59.8 ± 4.7 years) women who completed supervised combined exercise training. Four linear models were applied to examine associations between DNA methylation, cardiorespiratory fitness (VO₂ peak), and exercise intervention (pre- vs. post-training), while adjusting for age, fat percentage, and estimated immune-cell proportions (EpiDISH). Interaction terms were tested to assess whether immune cell composition or menopausal status modulated the relationship between VO₂ peak, exercise response, and DNA methylation.
Results
After adjusting for baseline values using analysis of covariance (ANCOVA), no statistically significant between-group differences were observed in the estimated immune cell proportions (FDR > 0.05). In PostM, exercise-induced DNA methylation changes were significantly associated with baseline VO₂ peak and were modulated by B cells, CD4+ T cells, NK cells, and monocytes. Functional enrichment highlighted pathways involved in lipid kinase regulation, nucleobase metabolism, and membrane organization.
Conclusion
Postmenopausal women showed distinct epigenetic patterns in response to exercise, although these differences must be interpreted cautiously given the small premenopausal sample size. These results suggest potential immune cell–associated DNA methylation markers to inform personalized exercise strategies supporting healthy aging in women.
更年期与免疫衰老和免疫谱改变有关，可能降低免疫能力。体育锻炼可以通过调节健康相关基因的DNA甲基化来抵消这些变化。方法：这项观察性生物信息学研究使用来自巴西队列的两个公开数据集（Illumina MethylationEPIC 850K）分析了来自全血的全基因组DNA甲基化谱。分析包括前置(PreM n = 13;34 ±4.7 年)和绝经后(59.8 n = 49 PostM; ±4.7 年)女性完成指导运动训练相结合。应用四个线性模型来检查DNA甲基化，心肺健康（vo2峰值）和运动干预（训练前与训练后）之间的关系，同时调整年龄，脂肪百分比和估计的免疫细胞比例（EpiDISH）。相互作用项进行测试，以评估免疫细胞组成或绝经状态是否调节vo2峰值、运动反应和DNA甲基化之间的关系。结果：在使用协方差分析（ANCOVA）调整基线值后，估计免疫细胞比例在组间无统计学差异（FDR > 0.05）。在PostM中，运动诱导的DNA甲基化变化与基线vo2峰值显著相关，并受到B细胞、CD4+ T细胞、NK细胞和单核细胞的调节。功能富集强调了涉及脂激酶调节、核碱基代谢和膜组织的途径。结论：绝经后妇女对运动表现出明显的表观遗传模式，尽管考虑到绝经前样本量小，这些差异必须谨慎解释。这些结果表明，潜在的免疫细胞相关DNA甲基化标记可以为支持女性健康衰老的个性化运动策略提供信息。
{"title":"Immune cell–associated DNA methylation responses to exercise in women: A bioinformatics analysis comparing pre- and postmenopausal stages","authors":"Guilherme da Silva Rodrigues , Natalia Yumi Noronha , Andressa Crystine da Silva Sobrinho , Bernadette Jones-Freeman , Robin Grolaux , Camila Fernanda Cunha Brandao , Julio Sergio Marchini , Lígia Moriguchi Watanabe , Carla Barbosa Nonino , Andrew Teschendorff , Nir Eynon , Carlos Roberto Bueno Júnior , Macsue Jacques","doi":"10.1016/j.exger.2025.112996","DOIUrl":"10.1016/j.exger.2025.112996","url":null,"abstract":"<div><h3>Introduction</h3><div>Menopause is associated with immunosenescence and altered immune profiles, potentially reducing immune competence. Physical exercise may counteract these changes by modulating DNA methylation in fitness-related genes.</div></div><div><h3>Methods</h3><div>This observational bioinformatics study analyzed genome-wide DNA methylation profiles derived from whole blood using two publicly available datasets from Brazilian cohorts (Illumina MethylationEPIC 850K). The analysis included pre- (PreM, <em>n</em> = 13; 34 ± 4.7 years) and postmenopausal (PostM, <em>n</em> = 49; 59.8 ± 4.7 years) women who completed supervised combined exercise training. Four linear models were applied to examine associations between DNA methylation, cardiorespiratory fitness (VO₂ peak), and exercise intervention (pre- vs. post-training), while adjusting for age, fat percentage, and estimated immune-cell proportions (EpiDISH). Interaction terms were tested to assess whether immune cell composition or menopausal status modulated the relationship between VO₂ peak, exercise response, and DNA methylation.</div></div><div><h3>Results</h3><div>After adjusting for baseline values using analysis of covariance (ANCOVA), no statistically significant between-group differences were observed in the estimated immune cell proportions (FDR > 0.05). In PostM, exercise-induced DNA methylation changes were significantly associated with baseline VO₂ peak and were modulated by B cells, CD4<sup>+</sup> T cells, NK cells, and monocytes. Functional enrichment highlighted pathways involved in lipid kinase regulation, nucleobase metabolism, and membrane organization.</div></div><div><h3>Conclusion</h3><div>Postmenopausal women showed distinct epigenetic patterns in response to exercise, although these differences must be interpreted cautiously given the small premenopausal sample size. These results suggest potential immune cell–associated DNA methylation markers to inform personalized exercise strategies supporting healthy aging in women.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 112996"},"PeriodicalIF":4.3,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784049","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}
Pub Date : 2025-12-15DOI: 10.1016/j.exger.2025.113000
Eun-Seon Noh , Jiwon Yang , Kai Wang , Seongryu Bae , Hyuntae Park
This study aimed to examine whether resting-state EEG markers show potential for distinguishing individuals as healthy control, mild cognitive impairment (MCI), and motoric cognitive risk syndrome (MCR), based on their levels of cognitive and motor decline. In this cross-sectional study, we enrolled 87 participants and classified them into three groups. Motor functions were measured by gait speed. Cognitive function was assessed by neuropsychologists using standardized tools, including the Mini-Mental State Examination (MMSE), the Symbol Digit Substitution Test (SDST), and the Paired Associates Learning (PAL) task. Resting-state EEG data were recorded for five minutes with eyes closed, using a 19-channel wireless EEG system. Our results showed that individuals with MCI and MCR exhibited increased frontal theta power and widespread default mode network (DMN) connectivity, reflecting underlying neuropsychological changes. These alterations were most pronounced in the MCR group and were associated with both cognitive and motor decline. Our findings highlight the potential of resting-state EEG as a biomarker for the early detection of cognitive and motor decline in community-dwelling older adults.
{"title":"Distinct patterns of cortical activity associated with cognitive and motor decline in community-dwelling older adults","authors":"Eun-Seon Noh , Jiwon Yang , Kai Wang , Seongryu Bae , Hyuntae Park","doi":"10.1016/j.exger.2025.113000","DOIUrl":"10.1016/j.exger.2025.113000","url":null,"abstract":"<div><div>This study aimed to examine whether resting-state EEG markers show potential for distinguishing individuals as healthy control, mild cognitive impairment (MCI), and motoric cognitive risk syndrome (MCR), based on their levels of cognitive and motor decline. In this cross-sectional study, we enrolled 87 participants and classified them into three groups. Motor functions were measured by gait speed. Cognitive function was assessed by neuropsychologists using standardized tools, including the Mini-Mental State Examination (MMSE), the Symbol Digit Substitution Test (SDST), and the Paired Associates Learning (PAL) task. Resting-state EEG data were recorded for five minutes with eyes closed, using a 19-channel wireless EEG system. Our results showed that individuals with MCI and MCR exhibited increased frontal theta power and widespread default mode network (DMN) connectivity, reflecting underlying neuropsychological changes. These alterations were most pronounced in the MCR group and were associated with both cognitive and motor decline. Our findings highlight the potential of resting-state EEG as a biomarker for the early detection of cognitive and motor decline in community-dwelling older adults.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 113000"},"PeriodicalIF":4.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776963","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}
Pub Date : 2025-12-13DOI: 10.1016/j.exger.2025.113004
Li Tao , Qinghuan Yang , Xinrong Zeng , Hao Yu , Jun Mu , Zhiwen Yan , Yinghong Tang
This cross-sectional study investigates the association between the Food Inflammation Scores of Individuals (FISI34, FISI26-USDA, FISI26-CHINA), derived from the Food Inflammation Index (FII), and sarcopenia in 5489 U.S. adults from the National Health and Nutrition Examination Survey (NHANES 2011–2018). Sarcopenia was defined using appendicular lean mass adjusted for body mass index (BMI). Logistic regression and restricted cubic spline analyses revealed significant positive associations between higher FISI and sarcopenia prevalence, with odds ratios ranging from 1.13 to 1.39 in fully adjusted models. Stronger associations were observed in females, adults aged ≥40 years, Mexican Americans, and those with higher BMI or chronic conditions like hypertension and cardiovascular disease, though no significant interaction effects were observed (p-interaction >0.05). FISI, incorporating individual dietary intake and nutrient reference values, offers a personalized approach compared to the Dietary Inflammatory Index (DII), supporting the evaluation of targeted dietary strategies to address sarcopenia.
{"title":"Association between food inflammation scores of individuals and sarcopenia in U.S. adults: A cross-sectional study from NHANES 2011–2018","authors":"Li Tao , Qinghuan Yang , Xinrong Zeng , Hao Yu , Jun Mu , Zhiwen Yan , Yinghong Tang","doi":"10.1016/j.exger.2025.113004","DOIUrl":"10.1016/j.exger.2025.113004","url":null,"abstract":"<div><div>This cross-sectional study investigates the association between the Food Inflammation Scores of Individuals (FISI34, FISI26-USDA, FISI26-CHINA), derived from the Food Inflammation Index (FII), and sarcopenia in 5489 U.S. adults from the National Health and Nutrition Examination Survey (NHANES 2011–2018). Sarcopenia was defined using appendicular lean mass adjusted for body mass index (BMI). Logistic regression and restricted cubic spline analyses revealed significant positive associations between higher FISI and sarcopenia prevalence, with odds ratios ranging from 1.13 to 1.39 in fully adjusted models. Stronger associations were observed in females, adults aged ≥40 years, Mexican Americans, and those with higher BMI or chronic conditions like hypertension and cardiovascular disease, though no significant interaction effects were observed (p-interaction >0.05). FISI, incorporating individual dietary intake and nutrient reference values, offers a personalized approach compared to the Dietary Inflammatory Index (DII), supporting the evaluation of targeted dietary strategies to address sarcopenia.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 113004"},"PeriodicalIF":4.3,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764756","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}
Pub Date : 2025-12-13DOI: 10.1016/j.exger.2025.113002
Michaela Rippl , Martin Bidlingmaier , Linda Deissler , Sebastian Martini , Katharina Mueller , Sabine Schluessel , Ralf Schmidmaier , Júnia R.O.L. Schweizer , Olivia Tausendfreund , Laura Welscher , Michael Drey
Background
Loss of physical function is a growing health concern in aging populations. Resistance training, including strength training (ST) and power training (PT), is the main therapeutic approach, yet evidence regarding the most effective modality remains inconsistent. Soluble alpha klotho (sαKL) is a protein increasingly recognized for its role in muscle function and may serve as a biomarker of training responsiveness due to its association with aging, muscle integrity, and exercise-induced adaptions. Therefore, we aimed to investigate whether ST and PT differentially influence sαKL levels in older adults.
Methods
69 prefrail, community-dwelling older adults (65–94 years) were randomly assigned to 12 weeks of ST, PT, or a control group (ClinicalTrials.gov: NCT00783159). In a post hoc analysis serum sαKL levels and physical performance measures before and after the intervention were analyzed.
Results
23 participants were allocated to ST, 24 to PT and 22 to the control group. The participants had a mean age of 77 years, 70 % were female. There were no baseline differences between groups. Both ST and PT led to significant improvements in the Short Physical Performance Battery (SPPB) but only ST increased sαKL levels.
Conclusion
Twelve weeks of ST, but not PT, significantly increased circulating sαKL levels in pre-frail older adults. Given the beneficial health effects of increased sαKL, these findings suggest that ST may offer additional biological advantages relevant to healthy aging. sαKL may serve as a promising biomarker for training-induced adaptions, but prospective trials are needed to confirm long-term effects and further clarify underlying mechanisms.
{"title":"Strength but not power training increases soluble alpha klotho levels in pre-frail older adults","authors":"Michaela Rippl , Martin Bidlingmaier , Linda Deissler , Sebastian Martini , Katharina Mueller , Sabine Schluessel , Ralf Schmidmaier , Júnia R.O.L. Schweizer , Olivia Tausendfreund , Laura Welscher , Michael Drey","doi":"10.1016/j.exger.2025.113002","DOIUrl":"10.1016/j.exger.2025.113002","url":null,"abstract":"<div><h3>Background</h3><div>Loss of physical function is a growing health concern in aging populations. Resistance training, including strength training (ST) and power training (PT), is the main therapeutic approach, yet evidence regarding the most effective modality remains inconsistent. Soluble alpha klotho (sαKL) is a protein increasingly recognized for its role in muscle function and may serve as a biomarker of training responsiveness due to its association with aging, muscle integrity, and exercise-induced adaptions. Therefore, we aimed to investigate whether ST and PT differentially influence sαKL levels in older adults.</div></div><div><h3>Methods</h3><div>69 prefrail, community-dwelling older adults (65–94 years) were randomly assigned to 12 weeks of ST, PT, or a control group (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>: <span><span>NCT00783159</span><svg><path></path></svg></span>). In a post hoc analysis serum sαKL levels and physical performance measures before and after the intervention were analyzed.</div></div><div><h3>Results</h3><div>23 participants were allocated to ST, 24 to PT and 22 to the control group. The participants had a mean age of 77 years, 70 % were female. There were no baseline differences between groups. Both ST and PT led to significant improvements in the Short Physical Performance Battery (SPPB) but only ST increased sαKL levels.</div></div><div><h3>Conclusion</h3><div>Twelve weeks of ST, but not PT, significantly increased circulating sαKL levels in pre-frail older adults. Given the beneficial health effects of increased sαKL, these findings suggest that ST may offer additional biological advantages relevant to healthy aging. sαKL may serve as a promising biomarker for training-induced adaptions, but prospective trials are needed to confirm long-term effects and further clarify underlying mechanisms.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 113002"},"PeriodicalIF":4.3,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764739","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}
Pub Date : 2025-12-12DOI: 10.1016/j.exger.2025.112992
Rasoul Ebrahimi , Mojtaba Seifi , Mohammad Mahdi Masouri , Melika Ravari Nejad , Ghazal Azad , Amir Hossein Kabiri , Shokoofe Noori
Background
This study aims to thoroughly evaluate blood neurofilament light chain (NfL) levels in multiple sclerosis (MS) patients compared to controls and across various MS subtypes.
Methods
We conducted a systematic search of PubMed and Web of Science up to February 20, 2025, focusing on studies that reported blood NfL levels in individuals with MS and in control groups. Effect sizes were determined using Hedges' g, applying a random effects model for significant heterogeneity (I2 > 50 %), and a fixed effects model otherwise.
Results
From 1380 records, 68 studies with a total of 19,159 participants were included. Blood NfL levels were significantly higher in MS patients compared to controls (SMD = 0.78; 95 % CI [0.67, 0.89], p < 0.001; I2 = 87.29 %). We also found elevated NfL levels in all major MS subtypes: RRMS (SMD = 0.71; 95 % CI [0.52, 0.91], p < 0.001; I2 = 90.26 %), SPMS (SMD = 0.94; 95 % CI [0.60, 1.28], p < 0.001; I2 = 88.43 %), PPMS (SMD = 0.79; 95 % CI [0.16, 1.42], p = 0.01; I2 = 95.75 %), and combined PMS (SMD = 0.96; 95 % CI [0.79, 1.12], p < 0.001; I2 = 80.28 %) compared to controls. Also, GFAP levels were significantly higher in PMS than in RRMS.
Conclusions
Our findings highlight the potential of blood NfL as a useful biomarker for tracking disease progression and distinguishing MS subtypes. However, additional studies are essential to confirm its effectiveness in clinical settings (Graphical abstract).
{"title":"Blood neurofilament light chain in patients with multiple sclerosis: A systematic review and updated meta-analysis","authors":"Rasoul Ebrahimi , Mojtaba Seifi , Mohammad Mahdi Masouri , Melika Ravari Nejad , Ghazal Azad , Amir Hossein Kabiri , Shokoofe Noori","doi":"10.1016/j.exger.2025.112992","DOIUrl":"10.1016/j.exger.2025.112992","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to thoroughly evaluate blood neurofilament light chain (NfL) levels in multiple sclerosis (MS) patients compared to controls and across various MS subtypes.</div></div><div><h3>Methods</h3><div>We conducted a systematic search of PubMed and Web of Science up to February 20, 2025, focusing on studies that reported blood NfL levels in individuals with MS and in control groups. Effect sizes were determined using Hedges' g, applying a random effects model for significant heterogeneity (<em>I</em><sup>2</sup> > 50 %), and a fixed effects model otherwise.</div></div><div><h3>Results</h3><div>From 1380 records, 68 studies with a total of 19,159 participants were included. Blood NfL levels were significantly higher in MS patients compared to controls (SMD = 0.78; 95 % CI [0.67, 0.89], <em>p</em> < 0.001; I<sup>2</sup> = 87.29 %). We also found elevated NfL levels in all major MS subtypes: RRMS (SMD = 0.71; 95 % CI [0.52, 0.91], <em>p</em> < 0.001; I<sup>2</sup> = 90.26 %), SPMS (SMD = 0.94; 95 % CI [0.60, 1.28], p < 0.001; I<sup>2</sup> = 88.43 %), PPMS (SMD = 0.79; 95 % CI [0.16, 1.42], <em>p</em> = 0.01; I<sup>2</sup> = 95.75 %), and combined PMS (SMD = 0.96; 95 % CI [0.79, 1.12], <em>p</em> < 0.001; I<sup>2</sup> = 80.28 %) compared to controls. Also, GFAP levels were significantly higher in PMS than in RRMS.</div></div><div><h3>Conclusions</h3><div>Our findings highlight the potential of blood NfL as a useful biomarker for tracking disease progression and distinguishing MS subtypes. However, additional studies are essential to confirm its effectiveness in clinical settings (Graphical abstract).</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 112992"},"PeriodicalIF":4.3,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145737548","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}
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