Pub Date : 2026-01-01DOI: 10.1016/j.exger.2025.113009
Jiali Luo , Zefeng Tan , Pan Shang , Shuyun Huang , Yajing Liu , Yukai Wang , Haiqun Xie , Qi Chen
Amnestic mild cognitive impairment (aMCI) is the prodromal period of Alzheimer's disease without effective treatment. This research aimed to investigate the effects of accelerated intermittent theta burst stimulation (iTBS) combined with adaptive cognitive training (COG) on cognitive function in aMCI patients and explore the underlying neural mechanisms. Twenty-four aMCI patients participated in either the real (n = 12) or sham (n = 12) stimulation group. Both groups received adaptive COG, which comprised three sessions of real or sham iTBS delivered on the left dorsolateral prefrontal cortex (DLPFC) once a day for 14 days. The primary outcomes were the Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) scores. Secondary outcomes were changes in cortical plasticity measured by transcranial magnetic stimulation and brain activation monitored by functional near-infrared spectroscopy (fNIRS). Patients were evaluated before and after the intervention. Patients with aMCI who received iTBS combined with COG had a significant improvement in cognitive performance, as assessed by the ADAS-Cog and N-back. In the iTBS+COG group, cortical plasticity measured 30 min post-intervention correlated with ADAS-Cog changes (r = −0.59, p = 0.043). Furthermore, this plasticity was associated with 1-back activation (r = −0.58, p = 0.050), and 2-back activation correlated with ADAS-Cog changes (r = −0.59, p = 0.042). Accelerated iTBS targeted to the left DLPFC combined with adaptive COG promoted cognitive improvement in aMCI patients more effectively by modulating cortical plasticity and brain activation. Cortical plasticity and brain activation might be valuable measurements for understanding cognitive function (Chinese Clinical Trial Registry: ChiCTR2400087943).
{"title":"Accelerated intermittent theta burst stimulation combined with cognitive training modulates cortical plasticity and brain activation in patients with amnestic mild cognitive impairment","authors":"Jiali Luo , Zefeng Tan , Pan Shang , Shuyun Huang , Yajing Liu , Yukai Wang , Haiqun Xie , Qi Chen","doi":"10.1016/j.exger.2025.113009","DOIUrl":"10.1016/j.exger.2025.113009","url":null,"abstract":"<div><div>Amnestic mild cognitive impairment (aMCI) is the prodromal period of Alzheimer's disease without effective treatment. This research aimed to investigate the effects of accelerated intermittent theta burst stimulation (iTBS) combined with adaptive cognitive training (COG) on cognitive function in aMCI patients and explore the underlying neural mechanisms. Twenty-four aMCI patients participated in either the real (<em>n</em> = 12) or sham (n = 12) stimulation group. Both groups received adaptive COG, which comprised three sessions of real or sham iTBS delivered on the left dorsolateral prefrontal cortex (DLPFC) once a day for 14 days. The primary outcomes were the Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) scores. Secondary outcomes were changes in cortical plasticity measured by transcranial magnetic stimulation and brain activation monitored by functional near-infrared spectroscopy (fNIRS). Patients were evaluated before and after the intervention. Patients with aMCI who received iTBS combined with COG had a significant improvement in cognitive performance, as assessed by the ADAS-Cog and N-back. In the iTBS+COG group, cortical plasticity measured 30 min post-intervention correlated with ADAS-Cog changes (<em>r</em> = −0.59, <em>p</em> = 0.043). Furthermore, this plasticity was associated with 1-back activation (<em>r</em> = −0.58, <em>p</em> = 0.050), and 2-back activation correlated with ADAS-Cog changes (r = −0.59, <em>p</em> = 0.042). Accelerated iTBS targeted to the left DLPFC combined with adaptive COG promoted cognitive improvement in aMCI patients more effectively by modulating cortical plasticity and brain activation. Cortical plasticity and brain activation might be valuable measurements for understanding cognitive function (Chinese Clinical Trial Registry: ChiCTR2400087943).</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 113009"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806882","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 : 2026-01-01DOI: 10.1016/j.exger.2025.113012
Yuexin Zhang , Hongli Zhang , Hongtao Ma
Purpose
This study aimed to evaluate the effects of a 12-week adapted tango program on executive and cognitive function in older adults.
Methods
In this randomized controlled trial, fifty Chinese older adults (aged 60–69 years) were randomly assigned to either an adapted tango intervention group (n = 25) or a control group (n = 25) maintaining usual daily habits. The intervention group completed a 12-week adapted tango program (twice weekly, 60 min per session). Executive function was assessed using the Flanker task, Dimensional Change Card Sort (DCCS) task, and N-back task, while global cognition was measured with the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). A two-way repeated-measures ANOVA was performed to examine group × time interactions, followed by Bonferroni-adjusted post-hoc comparisons. Effect sizes were calculated using Cohen's d.
Results
Significant group × time interactions were found for Flanker reaction time (RT) and accuracy (p = 0.002 and p < 0.001), with improvements in the tango group but no changes in the control group. DCCS RT and accuracy also showed significant improvements (p < 0.001), while the control group exhibited no changes. Significant improvements were noted in N-back RT and accuracy (p = 0.008 and p < 0.001), with no changes observed in the control group. Additionally, MMSE total and subdomains (e.g., orientation) significantly improved (p < 0.001), with no changes in the controls. MoCA total and subdomains (e.g., visuospatial/executive) significantly improved (p < 0.001), while no changes were found in the control group.
Conclusion
The findings suggest that adapted tango may be an effective non-pharmacological intervention for enhancing executive and cognitive functions in older adults, with potential implications for promoting cognitive health in aging populations.
{"title":"The impact of adapted tango dance on cognitive and executive function in older adults: A randomized controlled trial","authors":"Yuexin Zhang , Hongli Zhang , Hongtao Ma","doi":"10.1016/j.exger.2025.113012","DOIUrl":"10.1016/j.exger.2025.113012","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to evaluate the effects of a 12-week adapted tango program on executive and cognitive function in older adults.</div></div><div><h3>Methods</h3><div>In this randomized controlled trial, fifty Chinese older adults (aged 60–69 years) were randomly assigned to either an adapted tango intervention group (<em>n</em> = 25) or a control group (n = 25) maintaining usual daily habits. The intervention group completed a 12-week adapted tango program (twice weekly, 60 min per session). Executive function was assessed using the Flanker task, Dimensional Change Card Sort (DCCS) task, and N-back task, while global cognition was measured with the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). A two-way repeated-measures ANOVA was performed to examine group × time interactions, followed by Bonferroni-adjusted post-hoc comparisons. Effect sizes were calculated using Cohen's d.</div></div><div><h3>Results</h3><div>Significant group × time interactions were found for Flanker reaction time (RT) and accuracy (<em>p</em> = 0.002 and <em>p</em> < 0.001), with improvements in the tango group but no changes in the control group. DCCS RT and accuracy also showed significant improvements (<em>p</em> < 0.001), while the control group exhibited no changes. Significant improvements were noted in N-back RT and accuracy (<em>p</em> = 0.008 and <em>p</em> < 0.001), with no changes observed in the control group. Additionally, MMSE total and subdomains (e.g., orientation) significantly improved (<em>p</em> < 0.001), with no changes in the controls. MoCA total and subdomains (e.g., visuospatial/executive) significantly improved (<em>p</em> < 0.001), while no changes were found in the control group.</div></div><div><h3>Conclusion</h3><div>The findings suggest that adapted tango may be an effective non-pharmacological intervention for enhancing executive and cognitive functions in older adults, with potential implications for promoting cognitive health in aging populations.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 113012"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829428","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 : 2026-01-01DOI: 10.1016/j.exger.2025.112999
Emma Treijtel , Hugo H. Wijnen , Nienke M.S. Golüke , Marian A.E. de van der Schueren , Lisette C.P.G.M. de Groot , Inge Groenendijk
Background
Hip fractures are common among older adults and typically occur alongside accumulating comorbidities and age-related musculoskeletal decline. While nutritional or exercise interventions can support recovery, the effect of a combined approach during rehabilitation remains unclear. This study aims to evaluate the effects, costs, and cost-effectiveness of a high-protein diet plus exercise intervention on functional recovery after a hip fracture.
Methods
This randomized controlled trial will include 102 older adults (≥65 years) recovering in a rehabilitation centre after a hip fracture. Participants will be randomly assigned (1:1) to the intervention or control group, stratified by sex and hospital. The intervention group will receive weekly dietitian support to comply with a high-protein diet (≥1.2 g/kg body weight/day) and will participate in progressive resistance exercise training twice weekly for 3 months. The control group will receive usual care. Due to the nature of the intervention, participant and staff blinding is not feasible, but analyses will be performed blinded. Measurements will be performed in the first week after surgery, at rehabilitation discharge, and 3 months after baseline. The primary outcome is physical functioning using the Short Physical Performance Battery. Secondary outcomes include handgrip strength, muscle mass, bone density, quality of life, daily functioning, nutritional status, bone metabolism biomarkers, and costs.
Discussion
The intervention is expected to enhance recovery, attenuate postoperative bone and muscle loss, and improve quality of life. Implementation into standard care could improve efficiency and cost-effectiveness.
{"title":"Optimizing recovery after a hip fracture: Protocol of a randomized controlled trial to study the effects, costs, and cost-effectiveness of a combined protein and exercise intervention in older adults after a hip fracture (ProBUS study)","authors":"Emma Treijtel , Hugo H. Wijnen , Nienke M.S. Golüke , Marian A.E. de van der Schueren , Lisette C.P.G.M. de Groot , Inge Groenendijk","doi":"10.1016/j.exger.2025.112999","DOIUrl":"10.1016/j.exger.2025.112999","url":null,"abstract":"<div><h3>Background</h3><div>Hip fractures are common among older adults and typically occur alongside accumulating comorbidities and age-related musculoskeletal decline. While nutritional or exercise interventions can support recovery, the effect of a combined approach during rehabilitation remains unclear. This study aims to evaluate the effects, costs, and cost-effectiveness of a high-protein diet plus exercise intervention on functional recovery after a hip fracture.</div></div><div><h3>Methods</h3><div>This randomized controlled trial will include 102 older adults (≥65 years) recovering in a rehabilitation centre after a hip fracture. Participants will be randomly assigned (1:1) to the intervention or control group, stratified by sex and hospital. The intervention group will receive weekly dietitian support to comply with a high-protein diet (≥1.2 g/kg body weight/day) and will participate in progressive resistance exercise training twice weekly for 3 months. The control group will receive usual care. Due to the nature of the intervention, participant and staff blinding is not feasible, but analyses will be performed blinded. Measurements will be performed in the first week after surgery, at rehabilitation discharge, and 3 months after baseline. The primary outcome is physical functioning using the Short Physical Performance Battery. Secondary outcomes include handgrip strength, muscle mass, bone density, quality of life, daily functioning, nutritional status, bone metabolism biomarkers, and costs.</div></div><div><h3>Discussion</h3><div>The intervention is expected to enhance recovery, attenuate postoperative bone and muscle loss, and improve quality of life. Implementation into standard care could improve efficiency and cost-effectiveness.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"213 ","pages":"Article 112999"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800828","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 : 2025-12-31DOI: 10.1016/j.exger.2025.113020
Tianle Zou , Jialin Liu , Li Zhang , Fang Liu , Enming Zhang , Xiaolong Wang , Jun Ju , Xiuxiu Huang , Qiong Fang
Background
This study aimed to adopt the network analysis approach to elucidate the complex associations among various domains of intrinsic capacity (IC) and the factors contributing to IC impairments among community-dwelling older adults based on the health ecological model.
Methods
A cross-sectional design was adopted, and older adults were recruited from local community health centers. IC was assessed using standardized tools recommended by the World Health Organization. The potential influencing factors of IC were collected based on the health ecological model, including personal characteristics, behavioral lifestyles, interpersonal networks, and living and working conditions. Network analyses were performed using a mixed graphical model to explore the complex relationships among IC domains and their associated factors.
Results
Among 3398 eligible participants, 2634 (77.52 %) individuals showed IC impairment, including mobility impairment (46.60 %), cognition impairment (39.38 %) and sensory impairment (35.00 %). Cognition and mobility functions were strongly interrelated (r = 0.24). The predictability values for IC domains were 27.7 % for cognition, 22.9 % for mobility, 15.4 % for psychology, 8.0 % for vitality and 7.5 % for sensory function. Education, age, monthly income, and the number of comorbidities showed close correlations with multiple IC domains. Furthermore, cognition showed specific positive links with lifestyles involving more mental engagement and intellectual work. Mobility was particularly associated with physical activity, including leisure time and household physical activities. Psychological capacity showed a specific association with sleep quality.
Conclusions
IC, particularly in the domains of cognition and mobility, was prevalently impaired among older adults. We identified both common and domain-specific factors associated with IC, offering insights for developing targeted interventions to enhance IC.
{"title":"Complex relationships among various domains of intrinsic capacity and their associated factors in community-dwelling older adults: A network analysis","authors":"Tianle Zou , Jialin Liu , Li Zhang , Fang Liu , Enming Zhang , Xiaolong Wang , Jun Ju , Xiuxiu Huang , Qiong Fang","doi":"10.1016/j.exger.2025.113020","DOIUrl":"10.1016/j.exger.2025.113020","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to adopt the network analysis approach to elucidate the complex associations among various domains of intrinsic capacity (IC) and the factors contributing to IC impairments among community-dwelling older adults based on the health ecological model.</div></div><div><h3>Methods</h3><div>A cross-sectional design was adopted, and older adults were recruited from local community health centers. IC was assessed using standardized tools recommended by the World Health Organization. The potential influencing factors of IC were collected based on the health ecological model, including personal characteristics, behavioral lifestyles, interpersonal networks, and living and working conditions. Network analyses were performed using a mixed graphical model to explore the complex relationships among IC domains and their associated factors.</div></div><div><h3>Results</h3><div>Among 3398 eligible participants, 2634 (77.52 %) individuals showed IC impairment, including mobility impairment (46.60 %), cognition impairment (39.38 %) and sensory impairment (35.00 %). Cognition and mobility functions were strongly interrelated (<em>r</em> = 0.24). The predictability values for IC domains were 27.7 % for cognition, 22.9 % for mobility, 15.4 % for psychology, 8.0 % for vitality and 7.5 % for sensory function. Education, age, monthly income, and the number of comorbidities showed close correlations with multiple IC domains. Furthermore, cognition showed specific positive links with lifestyles involving more mental engagement and intellectual work. Mobility was particularly associated with physical activity, including leisure time and household physical activities. Psychological capacity showed a specific association with sleep quality.</div></div><div><h3>Conclusions</h3><div>IC, particularly in the domains of cognition and mobility, was prevalently impaired among older adults. We identified both common and domain-specific factors associated with IC, offering insights for developing targeted interventions to enhance IC.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113020"},"PeriodicalIF":4.3,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893549","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 : 2025-12-31DOI: 10.1016/j.exger.2025.113019
Kang Chen , Guran Yu , Hao Li
Background
Cognitive impairment in older adults poses a growing public health challenge, yet accessible screening tools remain limited. We aimed to develop and validate an interpretable machine learning model for cognitive impairment prediction by routinely collecting clinical data.
Methods
We analyzed 1061 participants from the U.S. National Health and Nutrition Examination Survey (NHANES 2011–2014). Feature selection combined multivariable regression, restricted cubic splines, and the Boruta algorithm to identify 40 clinical, demographic, and socioeconomic variables. Twelve machine learning models (including Support Vector Machine (SVM), Extreme Gradient Boosting (XGBoost), and Random Forest (RF)) were trained and externally validated on NHANES 2001–2002 (n = 531). Model performance was evaluated by area under the receiver operating characteristic curve (AUC-ROC), calibration (Brier score), accuracy, and sensitivity. Additionally, an assessment of fairness was conducted across racial subgroups. Interpretability was enhanced via SHapley Additive exPlanations (SHAP).
Results
The SVM model demonstrated optimal generalizability, achieving an external validation AUC of 0.8265 (95 %CI: 0.7867–0.8582) with sustained calibration (Brier score = 0.1703). Subgroup analyses showed no statistically significant AUC differences (all P > 0.05). SHAP analysis identified socioeconomic factors, systemic inflammation indices, and metabolic markers as key predictors.
Limitations.
Generalizability may be limited to U.S. populations, and unmeasured biomarkers (e.g., amyloid-β) could affect prediction accuracy. Subgroup analyses for minorities were constrained by sample size.
Conclusion
Our interpretable prediction strategy enables rapid cognitive risk assessment using routine clinical data, providing a cost-effective decision support tool adaptable to electronic health record systems.
{"title":"Interpretable machine learning for cognitive impairment screening: Development and external validation of a clinical prediction model based on NHANES data","authors":"Kang Chen , Guran Yu , Hao Li","doi":"10.1016/j.exger.2025.113019","DOIUrl":"10.1016/j.exger.2025.113019","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive impairment in older adults poses a growing public health challenge, yet accessible screening tools remain limited. We aimed to develop and validate an interpretable machine learning model for cognitive impairment prediction by routinely collecting clinical data.</div></div><div><h3>Methods</h3><div>We analyzed 1061 participants from the U.S. National Health and Nutrition Examination Survey (NHANES 2011–2014). Feature selection combined multivariable regression, restricted cubic splines, and the Boruta algorithm to identify 40 clinical, demographic, and socioeconomic variables. Twelve machine learning models (including Support Vector Machine (SVM), Extreme Gradient Boosting (XGBoost), and Random Forest (RF)) were trained and externally validated on NHANES 2001–2002 (<em>n</em> = 531). Model performance was evaluated by area under the receiver operating characteristic curve (AUC-ROC), calibration (Brier score), accuracy, and sensitivity. Additionally, an assessment of fairness was conducted across racial subgroups. Interpretability was enhanced via SHapley Additive exPlanations (SHAP).</div></div><div><h3>Results</h3><div>The SVM model demonstrated optimal generalizability, achieving an external validation AUC of 0.8265 (95 %CI: 0.7867–0.8582) with sustained calibration (Brier score = 0.1703). Subgroup analyses showed no statistically significant AUC differences (all <em>P</em> > 0.05). SHAP analysis identified socioeconomic factors, systemic inflammation indices, and metabolic markers as key predictors.</div><div>Limitations.</div><div>Generalizability may be limited to U.S. populations, and unmeasured biomarkers (e.g., amyloid-β) could affect prediction accuracy. Subgroup analyses for minorities were constrained by sample size.</div></div><div><h3>Conclusion</h3><div>Our interpretable prediction strategy enables rapid cognitive risk assessment using routine clinical data, providing a cost-effective decision support tool adaptable to electronic health record systems.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113019"},"PeriodicalIF":4.3,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893557","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 : 2025-12-29DOI: 10.1016/j.exger.2025.113017
Hye-Young Park , Kyeezu Kim
Introduction
Metabolic syndrome (MetS) increases with age. Epigenetic alterations reflect lifelong biological and environmental influences on aging. MetS may contribute to epigenetic age acceleration (EAA) through inflammation and oxidative stress, while elevated EAA may, in turn, exacerbate metabolic dysfunction, but long-term evidence for this bidirectional association is limited.
Methods
We analyzed data from 1452 participants in the Korean Genome and Epidemiology Study at baseline (Wave 1), 10-year (Wave 5), and 20-year (Wave 10) follow-ups. MetS severity was defined by the number of diagnostic criteria, and DNA methylation-based EAA measures (PhenoAA, Grim2AA, DunedinPACE) at Wave 5 were included. Multivariable linear regression models examined the association between MetS and EAA both cross-sectionally (at Wave 5) and longitudinally (Wave 1 MetS – Wave 5 EAA and Wave 5 EAA – Wave 10 MetS). Mediation analysis examined whether EAA mediated the association between MetS severity across waves. All models were adjusted for chronological age, sex, smoking, drinking, physical activity, education, income, and body mass index.
Results
Cross-sectionally, all EAA measures were associated with higher MetS severity score (β ranged 0.37–1.26, all P < 0.05). Longitudinally, earlier MetS severity was associated with EAA (Grim2AA: β = 0.25; DunedinPACE: β = 0.78, all P < 0.05) and EAA was associated with later MetS severity (Grim2AA: β = 0.03; DunedinPACE: β = 0.01, all P < 0.05). EAA partially mediated the association between earlier and later MetS severity (1.6–3.1 % mediation proportion, P < 0.05).
Conclusion
Our findings suggest a bidirectional relationship between MetS and EAA, with biological aging potentially mediating metabolic deterioration. EAA may serve as both a marker and mediator of metabolic health, and a promising target for prevention and intervention.
{"title":"Bidirectional associations between metabolic syndrome and epigenetic age acceleration: A 20-year longitudinal study in midlife adults","authors":"Hye-Young Park , Kyeezu Kim","doi":"10.1016/j.exger.2025.113017","DOIUrl":"10.1016/j.exger.2025.113017","url":null,"abstract":"<div><h3>Introduction</h3><div>Metabolic syndrome (MetS) increases with age. Epigenetic alterations reflect lifelong biological and environmental influences on aging. MetS may contribute to epigenetic age acceleration (EAA) through inflammation and oxidative stress, while elevated EAA may, in turn, exacerbate metabolic dysfunction, but long-term evidence for this bidirectional association is limited.</div></div><div><h3>Methods</h3><div>We analyzed data from 1452 participants in the Korean Genome and Epidemiology Study at baseline (Wave 1), 10-year (Wave 5), and 20-year (Wave 10) follow-ups. MetS severity was defined by the number of diagnostic criteria, and DNA methylation-based EAA measures (PhenoAA, Grim2AA, DunedinPACE) at Wave 5 were included. Multivariable linear regression models examined the association between MetS and EAA both cross-sectionally (at Wave 5) and longitudinally (Wave 1 MetS – Wave 5 EAA and Wave 5 EAA – Wave 10 MetS). Mediation analysis examined whether EAA mediated the association between MetS severity across waves. All models were adjusted for chronological age, sex, smoking, drinking, physical activity, education, income, and body mass index.</div></div><div><h3>Results</h3><div>Cross-sectionally, all EAA measures were associated with higher MetS severity score (β ranged 0.37–1.26, all <em>P</em> < 0.05). Longitudinally, earlier MetS severity was associated with EAA (Grim2AA: β = 0.25; DunedinPACE: β = 0.78, all <em>P</em> < 0.05) and EAA was associated with later MetS severity (Grim2AA: β = 0.03; DunedinPACE: β = 0.01, all <em>P</em> < 0.05). EAA partially mediated the association between earlier and later MetS severity (1.6–3.1 % mediation proportion, <em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>Our findings suggest a bidirectional relationship between MetS and EAA, with biological aging potentially mediating metabolic deterioration. EAA may serve as both a marker and mediator of metabolic health, and a promising target for prevention and intervention.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113017"},"PeriodicalIF":4.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879782","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}
Immunonutrition refers to nutritional interventions that can improve immune function. The nutritional contents used in immunocytes include amino acids, vitamins, minerals, and flavonoids.
In this study, we examine the oxi-inflamm-aging theory, which illustrates the antioxidant effects of diet, immune system performance, and life span. According to this theory, if vitamin C is consumed in the early stages of life, it can increase life span. The main objective of this study was to investigate the potential role of key immunonutrients in modulating immune system activity and lifespan through antioxidant and anti-inflammatory mechanisms. Vitamin E can reduce the mortality caused by the disease by inhibiting the oxidative damage associated with aging and inducing the P21 signaling pathway as an anti-cancer pathway. Also, vitamin D can reduce aging by increasing the expression of skinhead-1 (SKN-1), a gene of stress response pathways, inhibition of toxicity caused by human β-amyloid, and insolubility of proteins as a molecular pathology of aging. Zinc can adjust the activity of thymus and its hormones, regulating natural killer cells/Natural killer cells (NK/NKT), causing the inherent immune system responses. Moreover, Selenium can reduce the disorders induced by oxidative damage via improving the function of thyroid and immune cells, as well as metabolic and cellular redox homeostasis. Flavonoids also protect against the use of old cells and aging-related phenotypes by protecting nerve cells and metabolic homeostasis, as well as inhibiting old cells and aging phenotypes. However, the findings are still incomplete, and more studies are needed to prove this claim. Therefore, we made this study with careful attention to future issues.
{"title":"Nutritional immunology in lifespan","authors":"Maryam Fallah , Fatemeh Naeini , Fatemeh Sadat Fahimzad , Ali Nouri , Sayyed Mehdi Rasooli Manesh , Alireza Haghighi , Soraiya Ebrahimpour-Koujan","doi":"10.1016/j.exger.2025.113015","DOIUrl":"10.1016/j.exger.2025.113015","url":null,"abstract":"<div><div>Immunonutrition refers to nutritional interventions that can improve immune function. The nutritional contents used in immunocytes include amino acids, vitamins, minerals, and flavonoids.</div><div>In this study, we examine the oxi-inflamm-aging theory, which illustrates the antioxidant effects of diet, immune system performance, and life span. According to this theory, if vitamin C is consumed in the early stages of life, it can increase life span. The main objective of this study was to investigate the potential role of key immunonutrients in modulating immune system activity and lifespan through antioxidant and anti-inflammatory mechanisms. Vitamin E can reduce the mortality caused by the disease by inhibiting the oxidative damage associated with aging and inducing the P21 signaling pathway as an anti-cancer pathway. Also, vitamin D can reduce aging by increasing the expression of skinhead-1 (SKN-1), a gene of stress response pathways, inhibition of toxicity caused by human β-amyloid, and insolubility of proteins as a molecular pathology of aging. Zinc can adjust the activity of thymus and its hormones, regulating natural killer cells/Natural killer cells (NK/NKT), causing the inherent immune system responses. Moreover, Selenium can reduce the disorders induced by oxidative damage via improving the function of thyroid and immune cells, as well as metabolic and cellular redox homeostasis. Flavonoids also protect against the use of old cells and aging-related phenotypes by protecting nerve cells and metabolic homeostasis, as well as inhibiting old cells and aging phenotypes. However, the findings are still incomplete, and more studies are needed to prove this claim. Therefore, we made this study with careful attention to future issues.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113015"},"PeriodicalIF":4.3,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145852011","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 : 2025-12-24DOI: 10.1016/j.exger.2025.113014
Myrthe Swart , Merle Geerds , Ivan Bautmans , Liza De Dobbeleer , Siddharta Lieten , Hugo Plácido da Silva , Rudi Tielemans , Cindel Bonneux , Yvonne Schoon , Geeske Peeters , Marcel Olde Rikkert , Dieuwke van Dartel , René Melis
Objectives
Hand grip measures offer potential indicators for recovery after hospitalization in older adults. We investigated prospective associations of the grip indicators maximal grip strength (GSmax), fatigue resistance (FR) and grip work (GW) with post-discharge functional limitations, health-related quality of life (HRQOL) and survival in older inpatients.
Methods
Grip indicators were evaluated at admission in general geriatric inpatients (GGI, n = 149) and geriatric hip fracture inpatients (HIP, n = 109). Questionnaires on functional limitations (10–40, lower is better) were collected for two weeks pre-admission, admission, three months follow-up, and six months follow-up. HRQOL (−4–10, higher is better) was assessed at admission, three months follow-up and six months follow-up. With individual growth modeling, we established the associations between grip indicators and the outcome trajectories. Three-month survival was analyzed using Cox proportional hazards models.
Results
In GGI, higher FR and GW were associated with better functional recovery from admission to three months follow-up (FR: B = −1.0 points per 10s increase, 95 %CI −1.9, −0.14; GW: B = −0.33 points per 100 kPa × s increase, 95 %CI −0.59, −0.07). HIP with higher grip indicators showed a better functional recovery towards three months follow-up (GSmax: B = −2.4 per 10 kPa increase, 95 %CI −3.9, −0.89; FR: B = −1.1, 95 %CI −2.4, 0.20; GW: B = −0.31, 95 %CI −0.61, −0.02). No or weak associations were found between grip indicators and HRQOL recovery. Hazard ratios pointed towards a better survival for better scores on grip indicators, but associations were not statistically significant.
Conclusion
Higher FR and GW at admission were associated with better recovery post-discharge in geriatric inpatients. Future research should examine the added clinical value of grip indicators in addition to known patient characteristics.
目的:手部握力测量为老年人住院后康复提供潜在指标。我们研究了握力指标最大握力(GSmax)、疲劳阻力(FR)和握力功(GW)与老年住院患者出院后功能限制、健康相关生活质量(HRQOL)和生存率的前瞻性关联。方法:对普通老年住院患者(GGI, n = 149)和老年髋部骨折住院患者(hip, n = 109)入院时握力指标进行评价。在入院前2周、入院后3个月、随访6个月收集功能限制问卷(10-40份,越低越好)。入院时评估HRQOL(-4-10,越高越好),随访3个月和6个月。通过个体成长模型,我们建立了握力指标与结果轨迹之间的关联。采用Cox比例风险模型分析3个月生存率。结果:在GGI,更高的FR和瓦与更好的功能恢复从入学到三个月随访(FR: B = -1.0分10年代增加,CI 95 % -1.9,-0.14;温伯格:B = -0.33分100 kPa × 年代增加,CI 95 % -0.59,-0.07)。臀部高控制指标显示更好的功能恢复对三个月随访(GSmax: B = 每10 -2.4 kPa增加,95年 % -3.9 CI, -0.89; FR: B = -1.1,-2.4 95 % CI, 0.20;温伯格:B = -0.31,-0.61 95 % CI, -0.02)。握力指标与HRQOL恢复之间无或弱关联。风险比表明,握力指标得分越高,存活率越高,但相关关系在统计上并不显著。结论:老年住院患者入院时FR和GW较高,出院后恢复较好。除了已知的患者特征外,未来的研究应检查握力指标的附加临床价值。
{"title":"Association of grip indicators with post-discharge recovery in geriatric and hip fracture inpatients","authors":"Myrthe Swart , Merle Geerds , Ivan Bautmans , Liza De Dobbeleer , Siddharta Lieten , Hugo Plácido da Silva , Rudi Tielemans , Cindel Bonneux , Yvonne Schoon , Geeske Peeters , Marcel Olde Rikkert , Dieuwke van Dartel , René Melis","doi":"10.1016/j.exger.2025.113014","DOIUrl":"10.1016/j.exger.2025.113014","url":null,"abstract":"<div><h3>Objectives</h3><div>Hand grip measures offer potential indicators for recovery after hospitalization in older adults. We investigated prospective associations of the grip indicators maximal grip strength (GSmax), fatigue resistance (FR) and grip work (GW) with post-discharge functional limitations, health-related quality of life (HRQOL) and survival in older inpatients.</div></div><div><h3>Methods</h3><div>Grip indicators were evaluated at admission in general geriatric inpatients (GGI, <em>n</em> = 149) and geriatric hip fracture inpatients (HIP, <em>n</em> = 109). Questionnaires on functional limitations (10–40, lower is better) were collected for two weeks pre-admission, admission, three months follow-up, and six months follow-up. HRQOL (−4–10, higher is better) was assessed at admission, three months follow-up and six months follow-up. With individual growth modeling, we established the associations between grip indicators and the outcome trajectories. Three-month survival was analyzed using Cox proportional hazards models.</div></div><div><h3>Results</h3><div>In GGI, higher FR and GW were associated with better functional recovery from admission to three months follow-up (FR: B = −1.0 points per 10s increase, 95 %CI −1.9, −0.14; GW: B = −0.33 points per 100 kPa × s increase, 95 %CI −0.59, −0.07). HIP with higher grip indicators showed a better functional recovery towards three months follow-up (GSmax: B = −2.4 per 10 kPa increase, 95 %CI −3.9, −0.89; FR: B = −1.1, 95 %CI −2.4, 0.20; GW: B = −0.31, 95 %CI −0.61, −0.02). No or weak associations were found between grip indicators and HRQOL recovery. Hazard ratios pointed towards a better survival for better scores on grip indicators, but associations were not statistically significant.</div></div><div><h3>Conclusion</h3><div>Higher FR and GW at admission were associated with better recovery post-discharge in geriatric inpatients. Future research should examine the added clinical value of grip indicators in addition to known patient characteristics.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113014"},"PeriodicalIF":4.3,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844317","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 : 2025-12-22DOI: 10.1016/j.exger.2025.113011
Qi Si , Lin Wu , Ximei Zhang , Guangyao Shi , Yingying Zhao , Yong Liu , Baoshun Hao , Shujie Yu , Bin Zhou , Yanling Zhang , Xiaoxian Qian , Dinghui Liu , Jianrui Zheng
Objective
Vascular aging is a critical risk factor for the development and progression of cardiovascular diseases. Age-related degenerative changes in vascular structure and function significantly promote the onset of various vascular disorders. Currently, the specific molecular mechanisms underlying age-associated vascular structural and functional decline have not been fully elucidated. Ginsenoside Rb1 (Rb1), as the primary active component of ginseng, has been confirmed to possess potential anti-aging properties. This study aims to investigate the protective effects of Rb1 on the aorta in aged mice and its underlying molecular mechanisms, thereby providing experimental evidence and theoretical support for the screening of natural anti-vascular aging drugs.
Methods
Naturally aged (72-week-old) male C57BL/6J mice were randomly divided into two groups (n = 5 per group) to receive intraperitoneal injections of either PBS (Old group) or 20 mg/kg Rb1 (Old + Rb1 group) for 6 weeks. Young mice (12-week-old, n = 5) served as controls. Aortic tissues were analyzed using histomorphology (hematoxylin and eosin, H&E), nanoscale biomechanics (Atomic Force Microscopy, AFM), senescence biomarkers (P21 immunofluorescence, SA-β-gal staining), apoptosis (TUNEL assay), and DNA damage (γ-H2AX).
Results
Compared to the Old group, Rb1 significantly alleviated structural remodeling of the aging aorta, restoring smooth muscle cell alignment and extracellular matrix. AFM analysis showed that Rb1 ameliorated the aging-induced impairments in nanobiomechanical properties (including elasticity, viscosity, and surface topography) induced by aging. Furthermore, Rb1 treatment downregulated the expression of P21 in the aorta, reduced the positive area percentage of SA-β-gal positivity, and decreased the proportion of TUNEL-positive apoptotic cells, although none of these indicators were comparable to the levels observed in the Young control group. Notably, Rb1 significantly alleviates the elevation of γ-H2AX (a marker of DNA double-strand breaks) in the aging aorta.
Conclusion
This study demonstrates that Rb1 attenuates DNA damage, thus ameliorating structural remodeling and biomechanical function of the aging aorta, and delaying vascular aging and apoptosis. Our findings suggest that Rb1 counteracts age-related aortic impairment, potentially by targeting the DNA damage pathway, which highlights its therapeutic potential against vascular aging.
{"title":"Ginsenoside Rb1 attenuates arterial aging by reducing DNA damage in aged mice","authors":"Qi Si , Lin Wu , Ximei Zhang , Guangyao Shi , Yingying Zhao , Yong Liu , Baoshun Hao , Shujie Yu , Bin Zhou , Yanling Zhang , Xiaoxian Qian , Dinghui Liu , Jianrui Zheng","doi":"10.1016/j.exger.2025.113011","DOIUrl":"10.1016/j.exger.2025.113011","url":null,"abstract":"<div><h3>Objective</h3><div>Vascular aging is a critical risk factor for the development and progression of cardiovascular diseases. Age-related degenerative changes in vascular structure and function significantly promote the onset of various vascular disorders. Currently, the specific molecular mechanisms underlying age-associated vascular structural and functional decline have not been fully elucidated. Ginsenoside Rb1 (Rb1), as the primary active component of ginseng, has been confirmed to possess potential anti-aging properties. This study aims to investigate the protective effects of Rb1 on the aorta in aged mice and its underlying molecular mechanisms, thereby providing experimental evidence and theoretical support for the screening of natural anti-vascular aging drugs.</div></div><div><h3>Methods</h3><div>Naturally aged (72-week-old) male C57BL/6J mice were randomly divided into two groups (<em>n</em> = 5 per group) to receive intraperitoneal injections of either PBS (Old group) or 20 mg/kg Rb1 (Old + Rb1 group) for 6 weeks. Young mice (12-week-old, n = 5) served as controls. Aortic tissues were analyzed using histomorphology (hematoxylin and eosin, H&E), nanoscale biomechanics (Atomic Force Microscopy, AFM), senescence biomarkers (P21 immunofluorescence, SA-β-gal staining), apoptosis (TUNEL assay), and DNA damage (γ-H2AX).</div></div><div><h3>Results</h3><div>Compared to the Old group, Rb1 significantly alleviated structural remodeling of the aging aorta, restoring smooth muscle cell alignment and extracellular matrix. AFM analysis showed that Rb1 ameliorated the aging-induced impairments in nanobiomechanical properties (including elasticity, viscosity, and surface topography) induced by aging. Furthermore, Rb1 treatment downregulated the expression of P21 in the aorta, reduced the positive area percentage of SA-β-gal positivity, and decreased the proportion of TUNEL-positive apoptotic cells, although none of these indicators were comparable to the levels observed in the Young control group. Notably, Rb1 significantly alleviates the elevation of γ-H2AX (a marker of DNA double-strand breaks) in the aging aorta.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that Rb1 attenuates DNA damage, thus ameliorating structural remodeling and biomechanical function of the aging aorta, and delaying vascular aging and apoptosis. Our findings suggest that Rb1 counteracts age-related aortic impairment, potentially by targeting the DNA damage pathway, which highlights its therapeutic potential against vascular aging.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"214 ","pages":"Article 113011"},"PeriodicalIF":4.3,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829423","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 : 2025-12-19DOI: 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}