Pub Date : 2026-03-01Epub Date: 2025-10-10DOI: 10.1016/j.exger.2025.112927
Zhenyuan Zhang , Cong Zhang , Yuan Zhao , Ya Gao , Yidan Zhang , Lan Zhang , Yutong Zheng , Xiangjian Zhang , Guofeng Yang , Jian Zhang
Objective
Age-related cognitive decline is associated with chronic neuroinflammation, and α-lipoic acid (LA) has been proposed as a potential cognitive enhancer. This study aimed to investigate whether LA ameliorates aging-related cognitive impairment by regulating neuroinflammation through the Peroxisome proliferator-activated receptor gamma (PPARγ)/nuclear factor kappa B (NF-κB) pathway in vivo and vitro.
Methods
Eighteen-month-old naturally aged C57BL/6 mice were treated with LA (100 mg/kg/day) for 8 weeks, followed by T maze behavioral tests. Immunofluorescence, PCR, and Western blot were used to assess neuroinflammation and PPARγ/NF-κB signaling pathway in the hippocampus. In vitro, D-galactose-induced BV2 cell was used as a senescent model. Cell viability was measured through CCK-8 assay. Subsequent PCR and Western blot analyses further delineated changes in inflammatory cytokines and PPARγ/NF-κB pathway.
Results
LA administration demonstrated significant cognitive-enhancing effects, accompanied by suppression of both microgliosis and astrocytosis, as well as a reduction in pro-inflammatory cytokines in the hippocampus of aged mice. Mechanistically, LA upregulated PPARγ expression and inhibited NF-κB phosphorylation. Furtherly, in vitro, LA attenuated senescence-associated inflammation, an effect that was abolished by the PPARγ antagonist GW9662, confirming the critical role of PPARγ signaling in mediating LA's anti-inflammatory action.
Conclusions
LA mitigated age-related cognitive deficits by modulating neuroinflammation through PPARγ/NF-κB suppression. Our findings highlighted the therapeutic potential of LA in aging-related cognitive decline and the role of the PPARγ/NF-κB axis in neuroinflammation regulation. As an exploratory study with a limited sample size, these findings offer promising insights that would benefit from future confirmation in larger cohorts.
{"title":"α-Lipoic acid mitigates age-related cognitive decline by modulating PPARγ/NF-κB-mediated neuroinflammation","authors":"Zhenyuan Zhang , Cong Zhang , Yuan Zhao , Ya Gao , Yidan Zhang , Lan Zhang , Yutong Zheng , Xiangjian Zhang , Guofeng Yang , Jian Zhang","doi":"10.1016/j.exger.2025.112927","DOIUrl":"10.1016/j.exger.2025.112927","url":null,"abstract":"<div><h3>Objective</h3><div>Age-related cognitive decline is associated with chronic neuroinflammation, and α-lipoic acid (LA) has been proposed as a potential cognitive enhancer. This study aimed to investigate whether LA ameliorates aging-related cognitive impairment by regulating neuroinflammation through the Peroxisome proliferator-activated receptor gamma (PPARγ)/nuclear factor kappa B (NF-κB) pathway in vivo and vitro.</div></div><div><h3>Methods</h3><div>Eighteen-month-old naturally aged C57BL/6 mice were treated with LA (100 mg/kg/day) for 8 weeks, followed by T maze behavioral tests. Immunofluorescence, PCR, and Western blot were used to assess neuroinflammation and PPARγ/NF-κB signaling pathway in the hippocampus. In vitro, D-galactose-induced BV2 cell was used as a senescent model. Cell viability was measured through CCK-8 assay. Subsequent PCR and Western blot analyses further delineated changes in inflammatory cytokines and PPARγ/NF-κB pathway.</div></div><div><h3>Results</h3><div>LA administration demonstrated significant cognitive-enhancing effects, accompanied by suppression of both microgliosis and astrocytosis, as well as a reduction in pro-inflammatory cytokines in the hippocampus of aged mice. Mechanistically, LA upregulated PPARγ expression and inhibited NF-κB phosphorylation. Furtherly, in vitro, LA attenuated senescence-associated inflammation, an effect that was abolished by the PPARγ antagonist GW9662, confirming the critical role of PPARγ signaling in mediating LA's anti-inflammatory action.</div></div><div><h3>Conclusions</h3><div>LA mitigated age-related cognitive deficits by modulating neuroinflammation through PPARγ/NF-κB suppression. Our findings highlighted the therapeutic potential of LA in aging-related cognitive decline and the role of the PPARγ/NF-κB axis in neuroinflammation regulation. As an exploratory study with a limited sample size, these findings offer promising insights that would benefit from future confirmation in larger cohorts.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"215 ","pages":"Article 112927"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282361","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 : 2026-03-01Epub Date: 2026-02-05DOI: 10.1016/j.exger.2026.113056
Sailee Sansgiri , Emmi Matikainen-Tervola , Merja Rantakokko , Taija Finni , Timo Rantalainen , Neil J. Cronin
Identification of ground contact timings (GCT) is critical for monitoring mobility in older adults. Laboratory methods are precise but limited to controlled environments, restricting their applicability in real-world settings. Treadmills allow extended measurements but fail to reflect the variability of overground walking. We evaluated the performance of deep learning models trained on treadmill data from young adults and their generalizability to treadmill and outdoor walking in older adults. We also explored transfer learning to enhance predictions by fine-tuning models with older adults’ treadmill and outdoor walking data. Foot-mounted inertial measurement unit (IMU) walking data was collected from 20 young adults on treadmills and 26 older adults on treadmills and outdoor level, incline, and decline terrains. Ground truth GCTs were derived using pressure insoles (young adults) and manually-annotated motion capture (older adults). A fully connected neural network, a convolutional neural network (CNN), and a bidirectional long short-term memory network were trained on IMU data. Transfer learning was applied incrementally by fine-tuning the best-performing model with older adults’ data. Model performance was evaluated on unseen outdoor data from 6 participants using F1-score and mean absolute error (MAE). The CNN achieved the highest F1-scores (0.9864 — treadmill, 0.9637 — outdoor level, 0.9538 — incline, and 0.9029 — decline walking) and the lowest MAE. Fine-tuning improved treadmill F1-scores up to n=10, while outdoor level scores plateaued at n=5. Decline walking showed poorer performance, highlighting the need for advanced modeling strategies. These findings underscore the potential of transfer learning for real-world mobility monitoring.
{"title":"From treadmill to outdoor overground walking: Enhancing ground contact timing detection for older adults using transfer learning","authors":"Sailee Sansgiri , Emmi Matikainen-Tervola , Merja Rantakokko , Taija Finni , Timo Rantalainen , Neil J. Cronin","doi":"10.1016/j.exger.2026.113056","DOIUrl":"10.1016/j.exger.2026.113056","url":null,"abstract":"<div><div>Identification of ground contact timings (GCT) is critical for monitoring mobility in older adults. Laboratory methods are precise but limited to controlled environments, restricting their applicability in real-world settings. Treadmills allow extended measurements but fail to reflect the variability of overground walking. We evaluated the performance of deep learning models trained on treadmill data from young adults and their generalizability to treadmill and outdoor walking in older adults. We also explored transfer learning to enhance predictions by fine-tuning models with older adults’ treadmill and outdoor walking data. Foot-mounted inertial measurement unit (IMU) walking data was collected from 20 young adults on treadmills and 26 older adults on treadmills and outdoor level, incline, and decline terrains. Ground truth GCTs were derived using pressure insoles (young adults) and manually-annotated motion capture (older adults). A fully connected neural network, a convolutional neural network (CNN), and a bidirectional long short-term memory network were trained on IMU data. Transfer learning was applied incrementally by fine-tuning the best-performing model with older adults’ data. Model performance was evaluated on unseen outdoor data from 6 participants using F1-score and mean absolute error (MAE). The CNN achieved the highest F1-scores (0.9864 — treadmill, 0.9637 — outdoor level, 0.9538 — incline, and 0.9029 — decline walking) and the lowest MAE. Fine-tuning improved treadmill F1-scores up to n=10, while outdoor level scores plateaued at n=5. Decline walking showed poorer performance, highlighting the need for advanced modeling strategies. These findings underscore the potential of transfer learning for real-world mobility monitoring.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"215 ","pages":"Article 113056"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138265","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 : 2026-03-01Epub Date: 2026-01-21DOI: 10.1016/j.exger.2026.113044
Xiaorong Ye , Dingqi Shi , Ruixuan Li , Yuxin Li , Luwen Zhang , Lei Shi , Yao Xiao
<div><h3>Background</h3><div>The burden of chronic diseases is known to be significantly increased by obesity, yet conventional measures like waist circumference (WC) and body mass index (BMI) do not accurately capture central adiposity. The Weight-Adjusted Waist Index (WWI), calculated as waist circumference (cm)/√weight (kg), has been proposed to assess abdominal fat distribution independent of overall body size and may theoretically outperform BMI and WC by reducing muscle-mass–related misclassification. Evidence regarding its association with multimorbidity remains limited. This study sought to elucidate these associations using nationally representative NHANES data and to verify the results in a prospective Chinese cohort (CHARLS).</div></div><div><h3>Method</h3><div>Adults ≥20 years in NHANES 2017–2023 were included, applying sampling weights. Multimorbidity was defined as the coexistence of ≥2 chronic conditions, identified based on self-reported physician-diagnosed diseases in both NHANES and CHARLS. In NHANES, multivariable logistic regression, RCS, GAM, interaction analysis and Sensitivity analyses were performed, adjusting for demographics, socioeconomic status, lifestyle behaviors, and dietary factors. ROC curve analysis was then performed to evaluate and compare the predictive performance of WWI, BMI, and WC. WWI, BMI, and WC were analyzed in separate regression models to avoid multicollinearity interference when comparing predictive performance. External validation was conducted using Cox regression and RCS in CHARLS 2011–2028, adjusting for demographic, socioeconomic, and lifestyle variables.</div></div><div><h3>Result</h3><div>In NHANES, WWI was significantly positively associated with multimorbidity (OR = 1.74; 95% CI: 1.59–1.90; <em>P</em> < 0.001). Participants in the highest quartile of WWI had over threefold higher odds of multimorbidity compared with those in the lowest quartile (OR = 3.04; 95% CI: 2.94–3.73; P < 0.001). RCS indicated a predominantly linear association, while GAM suggested a modest J-shaped pattern. Sex significantly modified the association (P for interaction <0.05). Sensitivity analysis in adults ≥45 years yielded consistent results. In the CHARLS cohort (<em>n</em> = 2985), higher WWI significantly predicted incident multimorbidity (HR = 1.14; 95% CI: 1.06–1.22). WWI showed the highest discriminative ability for multimorbidity (AUC = 0.709) compared with BMI and WC.</div></div><div><h3>Conclusions</h3><div>WWI remained a significant and consistent predictor of multimorbidity, demonstrating greater discriminatory ability than BMI or WC. While RCS suggested a predominantly linear association, GAM revealed potential non-linearity at extreme WWI levels, indicating that dose-response patterns warrant further confirmation. Validation in the CHARLS cohort supports temporal association, offering greater causal plausibility. Collectively, these results highlight WWI as a practical marker for identifying h
背景：众所周知，慢性疾病的负担会因肥胖而显著增加，但传统的测量方法如腰围（WC）和体重指数（BMI）并不能准确地捕捉到中心性肥胖。体重调整腰围指数（WWI），以腰围(cm)/体重（kg）计算，已被提出用于评估腹部脂肪分布独立于整体体型，理论上可能通过减少与肌肉质量相关的错误分类而优于BMI和WC。关于其与多病相关的证据仍然有限。本研究试图利用具有全国代表性的NHANES数据阐明这些关联，并在一个前瞻性的中国队列（CHARLS）中验证结果。方法：纳入NHANES 2017-2023中≥20 岁的成年人，应用抽样权。多病被定义为共存≥2种慢性疾病，根据NHANES和CHARLS中自我报告的医生诊断疾病来确定。在NHANES中，进行了多变量logistic回归、RCS、GAM、相互作用分析和敏感性分析，调整了人口统计学、社会经济地位、生活方式行为和饮食因素。然后进行ROC曲线分析，评价和比较WWI、BMI和WC的预测性能。WWI、BMI和WC在单独的回归模型中进行分析，以避免在比较预测性能时的多重共线性干扰。在CHARLS 2011-2028中使用Cox回归和RCS进行外部验证，调整人口统计学、社会经济和生活方式变量。结果：在NHANES中，WWI与多发病显著正相关（OR = 1.74;95% CI: 1.59-1.90; P ）结论：WWI仍然是多发病的显著且一致的预测因子，表现出比BMI或WC更强的区分能力。虽然RCS显示了主要的线性关联，但GAM显示了在极端WWI水平下潜在的非线性，表明剂量-反应模式有待进一步证实。CHARLS队列验证支持时间关联，提供更大的因果合理性。总的来说，这些结果突出了一战作为识别高风险个体和指导早期预防策略的实用标记。
{"title":"Association between weight-adjusted waist index (WWI) and multimorbidity: Evidence from NHANES and prospective validation in CHARLS","authors":"Xiaorong Ye , Dingqi Shi , Ruixuan Li , Yuxin Li , Luwen Zhang , Lei Shi , Yao Xiao","doi":"10.1016/j.exger.2026.113044","DOIUrl":"10.1016/j.exger.2026.113044","url":null,"abstract":"<div><h3>Background</h3><div>The burden of chronic diseases is known to be significantly increased by obesity, yet conventional measures like waist circumference (WC) and body mass index (BMI) do not accurately capture central adiposity. The Weight-Adjusted Waist Index (WWI), calculated as waist circumference (cm)/√weight (kg), has been proposed to assess abdominal fat distribution independent of overall body size and may theoretically outperform BMI and WC by reducing muscle-mass–related misclassification. Evidence regarding its association with multimorbidity remains limited. This study sought to elucidate these associations using nationally representative NHANES data and to verify the results in a prospective Chinese cohort (CHARLS).</div></div><div><h3>Method</h3><div>Adults ≥20 years in NHANES 2017–2023 were included, applying sampling weights. Multimorbidity was defined as the coexistence of ≥2 chronic conditions, identified based on self-reported physician-diagnosed diseases in both NHANES and CHARLS. In NHANES, multivariable logistic regression, RCS, GAM, interaction analysis and Sensitivity analyses were performed, adjusting for demographics, socioeconomic status, lifestyle behaviors, and dietary factors. ROC curve analysis was then performed to evaluate and compare the predictive performance of WWI, BMI, and WC. WWI, BMI, and WC were analyzed in separate regression models to avoid multicollinearity interference when comparing predictive performance. External validation was conducted using Cox regression and RCS in CHARLS 2011–2028, adjusting for demographic, socioeconomic, and lifestyle variables.</div></div><div><h3>Result</h3><div>In NHANES, WWI was significantly positively associated with multimorbidity (OR = 1.74; 95% CI: 1.59–1.90; <em>P</em> < 0.001). Participants in the highest quartile of WWI had over threefold higher odds of multimorbidity compared with those in the lowest quartile (OR = 3.04; 95% CI: 2.94–3.73; P < 0.001). RCS indicated a predominantly linear association, while GAM suggested a modest J-shaped pattern. Sex significantly modified the association (P for interaction <0.05). Sensitivity analysis in adults ≥45 years yielded consistent results. In the CHARLS cohort (<em>n</em> = 2985), higher WWI significantly predicted incident multimorbidity (HR = 1.14; 95% CI: 1.06–1.22). WWI showed the highest discriminative ability for multimorbidity (AUC = 0.709) compared with BMI and WC.</div></div><div><h3>Conclusions</h3><div>WWI remained a significant and consistent predictor of multimorbidity, demonstrating greater discriminatory ability than BMI or WC. While RCS suggested a predominantly linear association, GAM revealed potential non-linearity at extreme WWI levels, indicating that dose-response patterns warrant further confirmation. Validation in the CHARLS cohort supports temporal association, offering greater causal plausibility. Collectively, these results highlight WWI as a practical marker for identifying h","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"215 ","pages":"Article 113044"},"PeriodicalIF":4.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146042325","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 : 2026-02-01Epub Date: 2026-01-12DOI: 10.1016/j.exger.2026.113033
Yan Lv , Yongjun Du , Peng Lin , Jiamian Liu , Shaoquan Pu , Sheng Lu
Background
Osteoporosis and sarcopenia are age-related degenerative diseases that frequently co-occur in the older adults, yet their shared molecular mechanisms remain poorly understood. This study aimed to identify common biomarkers.
Methods
By utilizing the GEO database, differential and enrichment analyses were conducted to identify genes that are commonly expressed in both diseases. Subsequently, key genes were identified through four types of machine learning and six types of immune infiltration analyses. Finally, the Dual Condition Sarcopenia and Osteoporosis (DSO) model was established by combining bilateral ovariectomy with natural aging to validate the key genes.
Results
A total of 577 and 625 genes were identified in the osteoporosis (GSE156508) and sarcopenia (GSE226151), respectively. GO, KEGG, and GSEA analyses revealed that osteoporosis-related genes were enriched in muscle development and myogenesis pathways, while sarcopenia-related genes were linked to osteoclast differentiation and inflammatory responses. Venn analysis identified 20 genes shared by both diseases. Four machine learning algorithms identified five key genes: APOC1, ENPP5, FBXL22, IRS1, and PAQR4. Among them, PAQR4 showed the highest predictive value in ROC analysis and was consistently downregulated in both training and validation datasets. Immune infiltration analysis indicated altered neutrophil levels, notably reduced in osteoporotic skeletal muscle. Experimental validation confirmed decreased PAQR4 expression in both bone and muscle tissues of the DSO model.
Conclusions
These findings highlight PAQR4 as a potential biomarker and a candidate molecule of interest for osteosarcopenia.
{"title":"Exploring the molecular intersections of osteoporosis and sarcopenia: An integrated bioinformatics and experimental validation","authors":"Yan Lv , Yongjun Du , Peng Lin , Jiamian Liu , Shaoquan Pu , Sheng Lu","doi":"10.1016/j.exger.2026.113033","DOIUrl":"10.1016/j.exger.2026.113033","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis and sarcopenia are age-related degenerative diseases that frequently co-occur in the older adults, yet their shared molecular mechanisms remain poorly understood. This study aimed to identify common biomarkers.</div></div><div><h3>Methods</h3><div>By utilizing the GEO database, differential and enrichment analyses were conducted to identify genes that are commonly expressed in both diseases. Subsequently, key genes were identified through four types of machine learning and six types of immune infiltration analyses. Finally, the Dual Condition Sarcopenia and Osteoporosis (DSO) model was established by combining bilateral ovariectomy with natural aging to validate the key genes.</div></div><div><h3>Results</h3><div>A total of 577 and 625 genes were identified in the osteoporosis (GSE156508) and sarcopenia (GSE226151), respectively. GO, KEGG, and GSEA analyses revealed that osteoporosis-related genes were enriched in muscle development and myogenesis pathways, while sarcopenia-related genes were linked to osteoclast differentiation and inflammatory responses. Venn analysis identified 20 genes shared by both diseases. Four machine learning algorithms identified five key genes: APOC1, ENPP5, FBXL22, IRS1, and PAQR4. Among them, PAQR4 showed the highest predictive value in ROC analysis and was consistently downregulated in both training and validation datasets. Immune infiltration analysis indicated altered neutrophil levels, notably reduced in osteoporotic skeletal muscle. Experimental validation confirmed decreased PAQR4 expression in both bone and muscle tissues of the DSO model.</div></div><div><h3>Conclusions</h3><div>These findings highlight PAQR4 as a potential biomarker and a candidate molecule of interest for osteosarcopenia.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113033"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979553","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 : 2026-02-01Epub Date: 2026-01-10DOI: 10.1016/j.exger.2026.113030
Xiaoying Ren , Yong Tian , Juan Tian , Guang Wang , Jia Liu
Background
Cardiovascular-kidney-metabolic (CKM) syndrome is a progressive disorder resulting from the intricate interactions among obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). Remnant cholesterol (RC) has been shown to be associated with the risk of CKM syndrome progression. However, the combined effects of RC and high-sensitivity C-reactive protein (hs-CRP) on CKM syndrome progression remain unclear. This study evaluated the association between the remnant cholesterol inflammatory index (RCII) and CKM progression risk.
Methods
Data from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. Logistic regression models were employed to investigate the association between the baseline RCII and advanced CKM stages. Kaplan-Meier analysis was conducted to assess the cumulative incidence of CVD across RCII quartiles in individuals with CKM stages 0–3. Cox regression models were used to examine the associations of the baseline RCII and cumulative RCII (CumRCII) with the risk of new-onset CVD among individuals with CKM stages 0–3.
Results
In the baseline analysis, each standard deviation (SD) increase in the RCII was associated with a 26% greater risk of advanced CKM stages (odds ratio (OR): 1.26, 95% CI: 1.20–1.34). During the 7-year follow-up, 1483 (21.5%) participants with CKM stages 0–3 developed CVD. The cumulative incidence of CVD progressively increased across RCII quartiles, from 17.02% in Q1 to 25.75% in Q4. After full adjustment, compared with that in RCII Q1, CVD risk was 19% greater in RCII Q3 (hazard ratio (HR): 1.19, 95% CI: 1.02–1.39) and 29% greater in RCII Q4 (HR: 1.29, 95% CI: 1.11–1.51). Participants with CumRCII levels that exceeded 29.49 had a significantly increased risk of new-onset CVD (HR: 1.41, 95% CI: 1.10–1.80).
Conclusions
Higher baseline RCII and CumRCII were associated with an increased CVD risk in participants with CKM stages 0–3. Early intervention in those with elevated RCII may help prevent CKM progression.
{"title":"Predictive value of remnant cholesterol inflammatory index for cardiovascular-kidney-metabolic syndrome progression: A prospective cohort study","authors":"Xiaoying Ren , Yong Tian , Juan Tian , Guang Wang , Jia Liu","doi":"10.1016/j.exger.2026.113030","DOIUrl":"10.1016/j.exger.2026.113030","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular-kidney-metabolic (CKM) syndrome is a progressive disorder resulting from the intricate interactions among obesity, diabetes, chronic kidney disease (CKD), and cardiovascular disease (CVD). Remnant cholesterol (RC) has been shown to be associated with the risk of CKM syndrome progression. However, the combined effects of RC and high-sensitivity C-reactive protein (hs-CRP) on CKM syndrome progression remain unclear. This study evaluated the association between the remnant cholesterol inflammatory index (RCII) and CKM progression risk.</div></div><div><h3>Methods</h3><div>Data from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. Logistic regression models were employed to investigate the association between the baseline RCII and advanced CKM stages. Kaplan-Meier analysis was conducted to assess the cumulative incidence of CVD across RCII quartiles in individuals with CKM stages 0–3. Cox regression models were used to examine the associations of the baseline RCII and cumulative RCII (CumRCII) with the risk of new-onset CVD among individuals with CKM stages 0–3.</div></div><div><h3>Results</h3><div>In the baseline analysis, each standard deviation (SD) increase in the RCII was associated with a 26% greater risk of advanced CKM stages (odds ratio (OR): 1.26, 95% CI: 1.20–1.34). During the 7-year follow-up, 1483 (21.5%) participants with CKM stages 0–3 developed CVD. The cumulative incidence of CVD progressively increased across RCII quartiles, from 17.02% in Q1 to 25.75% in Q4. After full adjustment, compared with that in RCII Q1, CVD risk was 19% greater in RCII Q3 (hazard ratio (HR): 1.19, 95% CI: 1.02–1.39) and 29% greater in RCII Q4 (HR: 1.29, 95% CI: 1.11–1.51). Participants with CumRCII levels that exceeded 29.49 had a significantly increased risk of new-onset CVD (HR: 1.41, 95% CI: 1.10–1.80).</div></div><div><h3>Conclusions</h3><div>Higher baseline RCII and CumRCII were associated with an increased CVD risk in participants with CKM stages 0<strong>–</strong>3. Early intervention in those with elevated RCII may help prevent CKM progression.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113030"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954737","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 : 2026-02-01Epub Date: 2026-01-22DOI: 10.1016/j.exger.2026.113041
Jiadong Qiu , Xiongying Song , Jian Wang , Sungmin Kim
Objective
To compare community-feasible exercise effects on cognition and explore muscle–brain axis mechanisms in older adults.
Methods
In this a single-blind, five-arm randomized controlled trial, participants were allocated to 12-form Chen-style Tai Chi (CTC12), 24-form Yang-style Tai Chi (TC24), square dancing (SD), walking, or control for 12 weeks (two sessions/week). Global cognition was assessed using Beijing Chinese MoCA. Body composition was evaluated using multifrequency bioimpedance: skeletal muscle mass (SMM), fat mass (FM), total body water, protein mass and basal metabolic rate (BMR). Physical performance was assessed using Short Physical Performance Battery (SPPB), maximal handgrip strength (HGS). Fasting interleukin-6 (IL-6) levels and other blood biomarkers were also measured.
Results
113 participants completed the intervention (mean age 62.3 years; 79.6% female). After 12 weeks training, MoCA scores were improved in CTC12 group (n = 22, Δ = +0.46, p = 0.0045) and SD group (n = 22, Δ = +0.50, p = 0.0046), with no change in TC24 group (n = 23), walking group (n = 23), and control group (n = 23). Physiologically, CTC12 group increased SMM and BMR with small SPPB/HGS gains and showed a significant reduction in IL-6 levels; SD group reduced BMI and FM and increased BMR and SPPB; TC24 group increased BMR only; walking showed no measurable changes. For correlation analyses, ΔMoCA was positively associated with ΔSMM (p = 0.014) and ΔBMR (p = 0.004) in the CTC12 group, and negatively associated with ΔBMI (p = 0.002) and ΔFM (p = 0.002) in the SD group.
Conclusions
CTC12, SD were associated with modest cognitive gains and distinct physiological patterns potentially linked to the muscle–brain axis, which may help guide exercise choices for older adults.
{"title":"Muscle–brain axis mechanisms linking community-based exercise to cognitive function in older adults: A five-arm randomized controlled trial","authors":"Jiadong Qiu , Xiongying Song , Jian Wang , Sungmin Kim","doi":"10.1016/j.exger.2026.113041","DOIUrl":"10.1016/j.exger.2026.113041","url":null,"abstract":"<div><h3>Objective</h3><div>To compare community-feasible exercise effects on cognition and explore muscle–brain axis mechanisms in older adults.</div></div><div><h3>Methods</h3><div>In this a single-blind, five-arm randomized controlled trial, participants were allocated to 12-form Chen-style Tai Chi (CTC12), 24-form Yang-style Tai Chi (TC24), square dancing (SD), walking, or control for 12 weeks (two sessions/week). Global cognition was assessed using Beijing Chinese MoCA. Body composition was evaluated using multifrequency bioimpedance: skeletal muscle mass (SMM), fat mass (FM), total body water, protein mass and basal metabolic rate (BMR). Physical performance was assessed using Short Physical Performance Battery (SPPB), maximal handgrip strength (HGS). Fasting interleukin-6 (IL-6) levels and other blood biomarkers were also measured.</div></div><div><h3>Results</h3><div>113 participants completed the intervention (mean age 62.3 years; 79.6% female). After 12 weeks training, MoCA scores were improved in CTC12 group (<em>n</em> = 22, Δ = +0.46, <em>p</em> = 0.0045) and SD group (n = 22, Δ = +0.50, <em>p</em> = 0.0046), with no change in TC24 group (<em>n</em> = 23), walking group (n = 23), and control group (n = 23). Physiologically, CTC12 group increased SMM and BMR with small SPPB/HGS gains and showed a significant reduction in IL-6 levels; SD group reduced BMI and FM and increased BMR and SPPB; TC24 group increased BMR only; walking showed no measurable changes. For correlation analyses, ΔMoCA was positively associated with ΔSMM (<em>p</em> = 0.014) and ΔBMR (<em>p</em> = 0.004) in the CTC12 group, and negatively associated with ΔBMI (<em>p</em> = 0.002) and ΔFM (p = 0.002) in the SD group.</div></div><div><h3>Conclusions</h3><div>CTC12, SD were associated with modest cognitive gains and distinct physiological patterns potentially linked to the muscle–brain axis, which may help guide exercise choices for older adults.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113041"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023518","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 : 2026-02-01Epub Date: 2026-01-16DOI: 10.1016/j.exger.2026.113042
Nadjia Amini , Laurence Lapauw , Jolan Dupont , Laura Vercauteren , Sebastiaan Dalle , Katrien Koppo , Sabine Verschueren , Jos Tournoy , Evelien Gielen
Background
Studies have shown that sarcopenia and its related parameters are associated with cognition. Preclinical evidence suggests that myokines, such as irisin, Brain-Derived Neurotrophic Factor(BDNF), myostatin and Insulin-like Growth Factor-1(IGF-1) might explain this relationship. This study aimed to explore the associations between sarcopenia-related parameters and cognition, and whether myokines influence this association.
Methods
Exploratory, cross-sectional analysis of data from the Exercise and Nutrition for Healthy AgeiNg (ENHANce,NCT03649698) study. Participants were older adults(≥65 years) with EWGSOP2-defined sarcopenia. Cognitive functioning was assessed by Mini-Mental State Examination(MMSE), Repeatable Battery for the Assessment of Neuropsychological Status(RBANS), Trail Making Test A&B(TMT), Stroop and Maze Test. Sarcopenia-related parameters were measured: Handgrip Strength, Chair Stand Test, appendicular Lean Mass(aLM), Gait Speed (GS) and Short Physical Performance Battery(SPPB). Serum myokines(IGF-1, irisin, myostatin, BDNF) were determined through ELISA. Associations between cognition and sarcopenia-related parameters were analyzed using multivariable regression, adjusting for potential confounders including myokines.
Results
Fifty-eight participants were included in this analysis (76.2 ± 6.7 years, ♀:65.5%). After adjustment for age, sex, body mass index, aLM was associated with MMSE(β = 0.193,p = 0.012), RBANS Total(β = 0.196,p = 0.007) and RBANS Attention(β = 0.215,p = 0.002), CST was associated with RBANS Language(β = −0.314,p = 0.030), SPPB was associated with Maze time(β = −0.364,p = 0.004) and TMT-B (β = −0.333,p = 0.013) and GS was associated with TMT-A(β = −0.324,p = 0.045). After adjustments for BDNF& IGF-1, the association between GS and TMT-A became non-significant. Irisin and myostatin did not influence the sarcopenia-cognition associations.
Conclusion
Sarcopenia-related parameters are associated with global and specific cognitive domains. BDNF may, partially, explain the association between muscle mass and MMSE. Additional research with larger sample size is needed to confirm these findings.
{"title":"Do myokines influence the associations between sarcopenia-related parameters and cognitive function in community-dwelling older adults: exploratory results from the ENHANce study","authors":"Nadjia Amini , Laurence Lapauw , Jolan Dupont , Laura Vercauteren , Sebastiaan Dalle , Katrien Koppo , Sabine Verschueren , Jos Tournoy , Evelien Gielen","doi":"10.1016/j.exger.2026.113042","DOIUrl":"10.1016/j.exger.2026.113042","url":null,"abstract":"<div><h3>Background</h3><div>Studies have shown that sarcopenia and its related parameters are associated with cognition. Preclinical evidence suggests that myokines, such as irisin, Brain-Derived Neurotrophic Factor(BDNF), myostatin and Insulin-like Growth Factor-1(IGF-1) might explain this relationship. This study aimed to explore the associations between sarcopenia-related parameters and cognition, and whether myokines influence this association.</div></div><div><h3>Methods</h3><div>Exploratory, cross-sectional analysis of data from the Exercise and Nutrition for Healthy AgeiNg (ENHANce,<span><span>NCT03649698</span><svg><path></path></svg></span>) study. Participants were older adults(≥65 years) with EWGSOP2-defined sarcopenia. Cognitive functioning was assessed by Mini-Mental State Examination(MMSE), Repeatable Battery for the Assessment of Neuropsychological Status(RBANS), Trail Making Test A&B(TMT), Stroop and Maze Test. Sarcopenia-related parameters were measured: Handgrip Strength, Chair Stand Test, appendicular Lean Mass(aLM), Gait Speed (GS) and Short Physical Performance Battery(SPPB). Serum myokines(IGF-1, irisin, myostatin, BDNF) were determined through ELISA. Associations between cognition and sarcopenia-related parameters were analyzed using multivariable regression, adjusting for potential confounders including myokines.</div></div><div><h3>Results</h3><div>Fifty-eight participants were included in this analysis (76.2 ± 6.7 years, ♀:65.5%). After adjustment for age, sex, body mass index, aLM was associated with MMSE(β = 0.193,<em>p</em> = 0.012), RBANS Total(β = 0.196,<em>p</em> = 0.007) and RBANS Attention(β = 0.215,<em>p</em> = 0.002), CST was associated with RBANS Language(β = −0.314,<em>p</em> = 0.030), SPPB was associated with Maze time(β = −0.364,<em>p</em> = 0.004) and TMT-B (β = −0.333,<em>p</em> = 0.013) and GS was associated with TMT-A(β = −0.324,<em>p</em> = 0.045). After adjustments for BDNF& IGF-1, the association between GS and TMT-A became non-significant. Irisin and myostatin did not influence the sarcopenia-cognition associations.</div></div><div><h3>Conclusion</h3><div>Sarcopenia-related parameters are associated with global and specific cognitive domains. BDNF may, partially, explain the association between muscle mass and MMSE. Additional research with larger sample size is needed to confirm these findings.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113042"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000199","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 : 2026-02-01Epub Date: 2026-01-14DOI: 10.1016/j.exger.2026.113036
Chunfeng Sun , Ping Qiu , Shuo Huang , Qihan Luo , Qing Ma , Piao Hu , Fangming Chen , Hongyan Wu , Chunxiao Chen
Aims
This study aims to systematically review existing literature to evaluate the association between telomere length (TL) and the risk of MASLD and its progression outcomes.
Materials and methods
PubMed, EMBASE, and Web of Science were searched for relevant studies up to May 27, 2025. Included studies were systematically reviewed to summarize the findings, with complementary quantitative analyses conducted using a random-effects model. This study was conducted in strict accordance with the PRISMA 2020 statement and was registered on the PROSPERO platform (CRD420251042478).
Results
Ultimately, 12 observational studies met the inclusion criteria. A limited number of high-quality cohort studies have consistently observed an association between shorter leukocyte TL (LTL) and an increased risk of MASLD. Evidence from cross-sectional studies appears more inconsistent and imprecise. Notably, cross-sectional analysis revealed a paradoxical increase in LTL among T2DM patients with MASLD, possibly reflecting a compensatory response to early-stage metabolic stress and insulin resistance; however, longitudinal evidence clarified that accelerated LTL attrition, rather than baseline length, serves as the critical driver and predictor of MASLD incidence. Despite consistent evidence indicating that shorter LTL may serve as a biomarker for severe MASLD progression, the interpretation of these findings is hampered by methodological limitations in current studies.
Conclusion
Current evidence suggests that shorter TL is a potential marker for MASLD risk, particularly supported by high-quality longitudinal data. While further quantitative analysis identified significant associations, the robustness of these results is compromised by the limited number of high-quality studies, alongside substantial heterogeneity and publication bias. Shorter TL may be associated with the adverse progression of MASLD. Future high-quality longitudinal studies are warranted to strengthen the body of evidence and establish their clinical utility.
本研究旨在系统地回顾现有文献，以评估端粒长度（TL）与MASLD风险及其进展结局之间的关系。检索截止到2025年5月27日的spubmed、EMBASE和Web of Science相关研究。系统回顾纳入的研究以总结研究结果，并使用随机效应模型进行补充性定量分析。本研究严格按照PRISMA 2020声明进行，并在PROSPERO平台上注册（CRD420251042478）。结果最终有12项观察性研究符合纳入标准。数量有限的高质量队列研究一致地观察到较短的白细胞TL （LTL）与MASLD风险增加之间的关联。来自横断面研究的证据似乎更不一致和不精确。值得注意的是，横断面分析揭示了T2DM合并MASLD患者LTL的矛盾增加，可能反映了对早期代谢应激和胰岛素抵抗的代偿反应；然而，纵向证据表明，加速LTL磨损，而不是基线长度，是MASLD发病率的关键驱动因素和预测因素。尽管一致的证据表明较短的LTL可能作为严重MASLD进展的生物标志物，但这些发现的解释受到当前研究方法限制的阻碍。结论：目前的证据表明，较短的TL是MASLD风险的潜在标志，特别是高质量的纵向数据支持。虽然进一步的定量分析确定了显著的关联，但这些结果的稳健性受到高质量研究数量有限、异质性和发表偏倚的影响。较短的生存期可能与MASLD的不良进展有关。未来有必要进行高质量的纵向研究，以加强证据体系并建立其临床应用。
{"title":"Telomere length and metabolic dysfunction-associated steatotic liver disease risk and progression: A systematic review and meta-analysis","authors":"Chunfeng Sun , Ping Qiu , Shuo Huang , Qihan Luo , Qing Ma , Piao Hu , Fangming Chen , Hongyan Wu , Chunxiao Chen","doi":"10.1016/j.exger.2026.113036","DOIUrl":"10.1016/j.exger.2026.113036","url":null,"abstract":"<div><h3>Aims</h3><div>This study aims to systematically review existing literature to evaluate the association between telomere length (TL) and the risk of MASLD and its progression outcomes.</div></div><div><h3>Materials and methods</h3><div>PubMed, EMBASE, and Web of Science were searched for relevant studies up to May 27, 2025. Included studies were systematically reviewed to summarize the findings, with complementary quantitative analyses conducted using a random-effects model. This study was conducted in strict accordance with the PRISMA 2020 statement and was registered on the PROSPERO platform (CRD420251042478).</div></div><div><h3>Results</h3><div>Ultimately, 12 observational studies met the inclusion criteria. A limited number of high-quality cohort studies have consistently observed an association between shorter leukocyte TL (LTL) and an increased risk of MASLD. Evidence from cross-sectional studies appears more inconsistent and imprecise. Notably, cross-sectional analysis revealed a paradoxical increase in LTL among T2DM patients with MASLD, possibly reflecting a compensatory response to early-stage metabolic stress and insulin resistance; however, longitudinal evidence clarified that accelerated LTL attrition, rather than baseline length, serves as the critical driver and predictor of MASLD incidence. Despite consistent evidence indicating that shorter LTL may serve as a biomarker for severe MASLD progression, the interpretation of these findings is hampered by methodological limitations in current studies.</div></div><div><h3>Conclusion</h3><div>Current evidence suggests that shorter TL is a potential marker for MASLD risk, particularly supported by high-quality longitudinal data. While further quantitative analysis identified significant associations, the robustness of these results is compromised by the limited number of high-quality studies, alongside substantial heterogeneity and publication bias. Shorter TL may be associated with the adverse progression of MASLD. Future high-quality longitudinal studies are warranted to strengthen the body of evidence and establish their clinical utility.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113036"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979552","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 : 2026-02-01Epub 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":"2026-02-01","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 : 2026-02-01Epub Date: 2026-01-09DOI: 10.1016/j.exger.2026.113028
Beatrice Arosio , Anna Picca
The muscle–brain axis integrates peripheral metabolic activity with central nervous system function. Among the endocrine signaling molecules regulating such crosstalk, the peptide hormone irisin released during muscle contraction seems to play relevant roles. Irisin is generated by the proteolytic cleavage of the fibronectin type III domain-containing protein 5 and has emerged as a key regulator of neurotrophic and metabolic adaptation. Although initially described as a myokine, irisin is also expressed in adipose and neural tissues, acting through autocrine, paracrine, and endocrine mechanisms. Irisin binds to the αV/β5 integrin receptor complex and activates a network of signaling pathways which promote mitochondrial biogenesis, autophagy, oxidative stress resistance, and modulation of inflammatory responses. Within the central nervous system, irisin induces brain-derived neurotrophic factor expression and contributes to synaptic plasticity, neurogenesis, and cognitive preservation. Experimental models show that irisin reduces amyloid burden, limits α-synuclein pathology, suppresses neuroinflammation, and stabilizes blood–brain barrier integrity, supporting a disease-modifying role in neurodegenerative conditions. In skeletal muscle, irisin stimulates myogenesis, enhances anabolic signaling, and improves metabolic efficiency, suggesting broader relevance for sarcopenia and age-related metabolic decline. Herein, we discuss irisin as a promising biomarker and a candidate therapeutic target for disorders characterized by concurrent muscle deterioration and cognitive impairment.
{"title":"Irisin and the muscle–brain axis: Mechanisms and translational potential","authors":"Beatrice Arosio , Anna Picca","doi":"10.1016/j.exger.2026.113028","DOIUrl":"10.1016/j.exger.2026.113028","url":null,"abstract":"<div><div>The muscle–brain axis integrates peripheral metabolic activity with central nervous system function. Among the endocrine signaling molecules regulating such crosstalk, the peptide hormone irisin released during muscle contraction seems to play relevant roles. Irisin is generated by the proteolytic cleavage of the fibronectin type III domain-containing protein 5 and has emerged as a key regulator of neurotrophic and metabolic adaptation. Although initially described as a myokine, irisin is also expressed in adipose and neural tissues, acting through autocrine, paracrine, and endocrine mechanisms. Irisin binds to the αV/β5 integrin receptor complex and activates a network of signaling pathways which promote mitochondrial biogenesis, autophagy, oxidative stress resistance, and modulation of inflammatory responses. Within the central nervous system, irisin induces brain-derived neurotrophic factor expression and contributes to synaptic plasticity, neurogenesis, and cognitive preservation. Experimental models show that irisin reduces amyloid burden, limits α-synuclein pathology, suppresses neuroinflammation, and stabilizes blood–brain barrier integrity, supporting a disease-modifying role in neurodegenerative conditions. In skeletal muscle, irisin stimulates myogenesis, enhances anabolic signaling, and improves metabolic efficiency, suggesting broader relevance for sarcopenia and age-related metabolic decline. Herein, we discuss irisin as a promising biomarker and a candidate therapeutic target for disorders characterized by concurrent muscle deterioration and cognitive impairment.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113028"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928645","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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