GeroScience最新文献

{"title":"Plasma proteomic signatures of social support and their association with cardiovascular disease and mortality: exploratory analyses in a national cohort study.","authors":"Pei Qin, Jessica Gong, Andrew Steptoe, Daisy Fancourt","doi":"10.1007/s11357-025-02031-8","DOIUrl":"10.1007/s11357-025-02031-8","url":null,"abstract":"<p><p>Social support has been related to cardiovascular disease (CVD) incidence and mortality in longitudinal cohort analyses, but the biological pathways underpinning this remain underexplored. This exploratory study examined the associations between social support and a wide range of proteomic biomarkers and performed the mediating effect of proteomic biomarkers in the association between social support and CVD and mortality to identify potential biological pathways linking social support to health outcomes. Data from 3141 adults over the age of 50 in the English Longitudinal Study of Ageing who had plasma proteome data were analyzed, with CVD and mortality outcomes followed up for 16 years following through Hospital Episode Statistics and the National Health Service's Central Registry. Linear and Cox regression analyses were used to identify proteins associated with social support, CVD, and mortality. Mediation analysis was then performed on the identified proteins to explore their role as a potential mediator between social support and CVD and mortality risk. Over a median of 15.8-year follow-up, 889 participants have died, and 627 developed CVD. Of 276 plasma proteins measured, greater social support was associated with lower levels of 13 proteins and higher TN-R levels, after adjusting for baseline socioeconomic confounders. We also identified 49 protein-CVD and 70 protein-mortality associations after minimal adjustments, including 11 and 14 proteins simultaneously associated with social support. All the significant proteins together mediated about 20.9% and 26.4% of the associations for CVD and mortality, respectively. The main enriched biological pathways involved death receptor activity and carbohydrate binding. Social support was related to a cluster of proteomic biomarkers, which may be linked to inflammation, apoptosis, and atherosclerosis/vascular pathways. The identified plasma proteins partly mediated the association between social support and CVD and mortality risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between relationship quality, proteomic signatures, and CVD and mortality development.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7645-7661"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavonoid intake and telomere length attrition among middle-aged women: a cross-sectional analysis of the Nurses' Health Study.","authors":"Sidong Li, Immaculata De Vivo, Sergio Davinelli, Martin Van Denburgh, Vincenzo Sorrenti, Giovanni Scapagnini, Howard D Sesso, Aedín Cassidy","doi":"10.1007/s11357-026-02126-w","DOIUrl":"10.1007/s11357-026-02126-w","url":null,"abstract":"<p><p>Although mechanistic studies support a beneficial effect of several dietary flavonoids on telomere length (TL), to our knowledge no studies have examined associations between habitual flavonoid intakes and TL in population-based studies. We examined the associations between habitual intake of major flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols and their polymers, and anthocyanins) and TL in a cross-sectional analysis of 4,944 disease-free females from the Nurses' Health Study (NHS). Flavonoid intakes were collected using food frequency questionnaire data, and TL was measured in peripheral blood leukocytes using quantitative real-time polymerase chain reaction. Multivariable-adjusted least squares mean leukocyte TL (z scores and corresponding standard error [SE]) for total and all flavonoid subclasses were calculated using generalized linear models. Although no individual flavonoid subclass was significantly associated with TL in the overall population, when we restricted analyses to younger and middle-aged participants (aged < 55 y), a higher anthocyanin intake associated with longer TL (least squares means ± SE: 0.06 ± 0.06 for the highest versus 0.24 ± 0.07 for the lowest quintile; P-trend = 0.042), corresponding to 6.6 (95% CI, 1.7-14.5) years of aging. In food-based analyses, participants aged < 55 y who consumed more berries had longer TL (Mean TL: 0.10 ± 0.04 for never/rarely; 0.21 ± 0.04 for ≤ 1 serving/week; 0.44 ± 0.26 for ≥ 2 servings/week; P = 0.033 for trend). Similarly, a higher anthocyanin intake was associated with longer TL among pre-menopausal females (0.46 ± 0.11 for the highest versus 0.02 ± 0.08 for the lowest quintile; P-trend = 0.001). Overall, habitual flavonoid intake was not associated with TL attrition in this cross-sectional analysis. However, in females aged < 55 y a higher anthocyanin intake was associated with longer TL, which raises the possibility that anthocyanin-rich foods may promote healthy aging and warrants further investigation with respect to age.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8325-8339"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial memory in Alzheimer's disease 5XFAD mice is enhanced by XPO1 inhibitor KPT-330.","authors":"Shi Quan Wong, Adia Ouellette, Laura Harrison, Avery McNamara, Rachel A Tam, Alexander Alexandrov, Acacia Nawrocik-Madrid, Jesus J Sanchez, Brett C Ginsburg, Arturo A Andrade, Louis R Lapierre","doi":"10.1007/s11357-026-02122-0","DOIUrl":"10.1007/s11357-026-02122-0","url":null,"abstract":"<p><p>The proteostatic decline in Alzheimer's disease is well established, and improvement in proteostasis could potentially delay cognitive impairment. One emerging entry point to modulate proteostasis is the regulation of nucleo-cytoplasmic partitioning of proteins across the nuclear pore via karyopherins. The nuclear exportin XPO1 is a key regulator of proteostasis by driving the assembly of ribosomes and by modulating the process of autophagy. We recently found that the XPO1 inhibitor KPT-330 (Selinexor), an FDA-approved drug against multiple myelomas, enhances proteostasis, leading to benefits in models of neurodegenerative diseases in C. elegans and Drosophila. Here, we find that KPT-330 increases autophagy in murine neuronal cells. In a murine model of Alzheimer's disease (5XFAD), KPT-330 improved spatial memory performance. Unexpectedly, general amyloid deposition in several brain regions was significantly increased by KPT-330, but specific regions, especially the thalamus, displayed significantly lower deposition, suggesting that XPO1 inhibition has regional-specific effects on proteostasis and amyloid plaque formation. Altogether, we conclude that, despite overall increases in amyloid plaque burden, XPO1 inhibition can improve cognition via spatially-specific reductions in amyloid deposition.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8341-8352"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrinsic capacity and mortality in community-dwelling octogenarians: a network analysis from the ilSIRENTE study.","authors":"Stefano Cacciatore, Bella Bravo, Rola S Zeidan, Riccardo Calvani, Hyung-Suk Alex Yoon, Matteo Tosato, Andrea Russo, Christiaan Leeuwenburgh, Stephen D Anton, Emanuele Marzetti, Francesco Landi","doi":"10.1007/s11357-026-02370-0","DOIUrl":"10.1007/s11357-026-02370-0","url":null,"abstract":"<p><p>Intrinsic capacity (IC) is a key construct within the healthy ageing framework. However, the correlations among IC domains and their association with health outcomes in very old adults remain unclear. This study aimed to characterise the relationships among IC domains using network analysis and to examine their association with mortality in community-dwelling octogenarians from the Invecchiamento e Longevità nel Sirente (ilSIRENTE) cohort. IC was calculated as a summary score rescaled to a 0-100 range across locomotion, cognition, vitality, psychological capacity, and sensory function, derived from routine home-based geriatric assessments (Minimum Data Set for Home Care instruments and supplementary tests). Assessments were conducted at designated centres, with home visits arranged for individuals unable to travel. The final sample included 319 community-dwelling adults aged ≥ 80 years (mean age 85.4 ± 4.8 years; 67.1% women). Network analysis suggested clustered relationships among vitality, psychological, and cognitive domains, whereas sensory domains appeared more peripheral. Hearing and vision were associated with locomotion, while their association with cognition appeared to be mediated by locomotion. In Cox proportional hazards models, higher locomotion scores were independently associated with lower mortality at 4 years [hazard ratio (HR) 0.86, 95% CI 0.80-0.93] and 7 years (HR 0.87, 95% CI 0.81-0.92). Each 10-point increase in IC was associated with lower mortality at 4 years (HR 0.67, 95% CI 0.58-0.77) and 7 years (HR 0.68, 95% CI 0.61-0.77). Among very old adults, locomotion emerged as a central functional domain linking sensory function, cognition, and survival within the IC framework. IC measures derived from routine assessments may provide a pragmatic approach for risk stratification and targeted interventions to promote healthy ageing.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7489-7503"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MASLD in the oldest-old: lack of association with cognition or functional autonomy and poor predictive utility of the hepatic steatosis index.","authors":"Maximilian Joseph Brol, Martin Groth, Frank Erhard Uschner, Juliana Stadtmann, Tina Schomacher, Jonel Trebicka, Michael Praktiknjo, Elena Vorona","doi":"10.1007/s11357-025-02060-3","DOIUrl":"10.1007/s11357-025-02060-3","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition increasingly recognized in aging populations. However, its clinical relevance in older adults-particularly in relation to sarcopenia, cognitive function, and rehabilitation outcomes-remains poorly defined. This retrospective observational study included in-patients admitted for geriatric rehabilitation in 2022 with available abdominal ultrasound. MASLD was defined according to AASLD/EASL criteria. Demographics, comorbidities, medications, and the hepatic steatosis index were recorded. Cognitive function (MMSE, clock-drawing, GDS), hand grip strength, mobility (Tinetti, Timed Up and Go), and functional status (Barthel Index, discharge autonomy) were assessed. Analyses included regression and AUROC, with significance at p below 0.05. MASLD was present in 49.6% of the study population. No significant association was observed between MASLD and cognitive impairment. Patients with higher hand grip strengths showed higher proportions of MASLD (p = 0.01). In this cohort, hepatic steatosis index has poor capacity to detect hepatic steatosis (AUC = 0.503, 95%-CI: 0.437-0.570). Furthermore, MASLD did not predict poorer functional outcomes following the rehabilitation stay. In adjusted models, Barthel Index -but neither MASLD nor hand grip strength- was independently associated with reduced functional autonomy at discharge (p = 0.006). In elderly patients, MASLD was associated with diabetes mellitus and higher hand grip strength, while sarcopenia was linked to a lower prevalence of steatosis. MASLD showed no association with cognitive performance, functional outcomes, or prediction by the hepatic steatosis index. These findings highlight age-specific characteristics of MASLD requiring tailored clinical approaches.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7613-7625"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facial skin aging: an integrative analysis of genetics, epigenetics, and lifestyle factors.","authors":"Rezvan Noroozi, Aleksandra Pisarek-Pacek, Bożena Wysocka, Kamila Migacz-Gruszka, Paulina Pruszkowska-Przybylska, Magdalena Kobus, Dagmara Lisman, Julia Zacharczuk, Joanna Rudnicka, Aleksandra Iljin, Kathryn C Fitzgerald, Małgorzata Michalczyk, Piotr Kaczka, Michał Krzysztofik, Maciej Kostrzewa, Aneta Sitek, Magdalena Spólnicka, Andrzej Ossowski, Wojciech Branicki, Ewelina Pośpiech","doi":"10.1007/s11357-025-02067-w","DOIUrl":"10.1007/s11357-025-02067-w","url":null,"abstract":"<p><p>Facial wrinkling is a prominent sign of aging, yet individuals exhibit unique trajectories of biological aging, contributing to the variability in facial appearance. Here, we present a pioneering study exploring the association between lifestyle choices, DNA methylation, and SNP genotypes with a range of facial skin aging phenotypes. The study demonstrated that age-related facial skin phenotypes are influenced by multiple environmental stressors. Epigenome-wide association analyses identified differentially methylated cytosines mapped to 151 loci, including novel genes associated with facial wrinkles, such as EDAR (cg02925966, p = 4.96 × 10^-8) and NRG1 (cg26267340, p = 4.64 × 10^-8), both involved in wound healing. Sensitivity analysis, conditioning on the top meQTLs, showed minor attenuation, suggesting an association independent of genetic variants. Accelerated epigenetic aging, measured in the blood of over 700 Polish individuals, was found to correlate with facial wrinkle area, photoaging, telangiectasias, and perceived facial age, with the GrimAge and FitAge clocks showing the most robust associations. Genome-wide SNP analysis identified rs73943403 (RP11-78F17.1, p = 3.72 × 10^-8) associated with wrinkle area and rs113125564 (ZC3H4, p = 1.23 × 10^-8) associated with perceived facial age, potentially implicating stress response and adiposity in skin aging. Finally, the study revealed the additive value of methylation and SNP data for predicting two continuous skin phenotypes, with 59.0% of the variation explained in facial wrinkle area and 26.2% in perceived facial age. The findings underscore the relevance of genetic and epigenetic factors, revealing novel candidate genes and molecular pathways involved in skin aging. These insights hold substantial translational value for dermatology, the cosmetics industry, and anti-aging strategies.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7627-7644"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explainable AI reveals temporal risk pathways in fall prediction: Extracting clinical insights from multi-horizon machine learning models.","authors":"Masoud Khani, David R Friedland, Michael Widlansky, Michael S Harris, Jazzmyne Adams, Lei Fan, Hyunkyoung Oh, Qiang Lu, Jake Luo","doi":"10.1007/s11357-026-02117-x","DOIUrl":"10.1007/s11357-026-02117-x","url":null,"abstract":"<p><p>Falls are a leading cause of injury in older adults, making risk prediction a clinical priority. While many machine learning (ML) models exist, they typically provide a static assessment, predicting risk for a single, fixed timeframe. This approach overlooks how the clinical drivers of risk evolve over time, failing to distinguish between acute factors that signal an imminent fall and chronic conditions that confer long-term vulnerability. This study uses an explainable ML framework across multiple time horizons to unlock deeper clinical insights into the temporal nature of fall risk. We conducted a retrospective, matched case-control study using electronic health record (EHR) data from 99,078 patients who fell and 99,078 matched controls. Seven ML models were trained to predict fall risk across seven distinct prediction windows (3, 6, 12, 24, 36, 48, and 60 months). The best-performing model for each horizon, consistently XGBoost, was interpreted using SHAP (SHapley Additive exPlanations) to identify how the importance of clinical and demographic predictors changed over time. A clear performance trade-off emerged across time horizons. Short-term models (3-12 months) delivered balanced discrimination (best model XGBoost, AUC ≈ 0.75), while long-term models became progressively better at identifying eventual fallers (recall ≈ 80% at 60 months) at the cost of lower specificity (≈ 46%). SHAP analysis revealed distinct temporal patterns: short-term risk was driven by acute conditions like syncope, respiratory symptoms, and urinary tract infections, while long-term risk was predicted by chronic, cumulative factors such as spondylopathies, nutritional deficiencies, and benign neoplasms. Three primary risk trajectories (increasing, steady, and decreasing) were identified, each corresponding to distinct underlying clinical profiles. Fall risk is a dynamic process, not a static state. By analyzing risk across multiple timeframes, we can distinguish between acute triggers requiring immediate intervention and chronic vulnerabilities demanding long-term management. This multi-horizon framework provides a data-driven foundation for a new paradigm in fall prevention: moving beyond generic \"high-risk\" labels to personalized, temporally aware strategies that align the type and timing of interventions with the specific nature of a patient's evolving risk.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8299-8324"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biopsychosocial frailty and the incident risk of cardio- and cerebrovascular diseases: an 8-year follow-up of the italian longitudinal study on aging.","authors":"Vincenzo Solfrizzi, Emanuele Scafato, Madia Lozupone, Carlo Custodero, Vittorio Dibello, Donato Cirrottola, Claudio Pace, Marika Rizzato, Andrea Schilardi, Claudia Gandin, Silvia Ghirini, Rodolfo Sardone, Antonio Daniele, Francesco Panza","doi":"10.1007/s11357-026-02135-9","DOIUrl":"10.1007/s11357-026-02135-9","url":null,"abstract":"<p><p>Biopsychosocial frailty, a new construct combining modifiable physical, psychological, and social domains, was associated with increased risk of dementia, mild cognitive impairment, and their subtypes. The aim of the present study was to estimate the role of biopsychosocial frailty on the incident risk of cardio- and cerebrovascular disease, i.e., myocardial infarction, peripheral artery disease (PAD), and definite stroke. From the eight municipalities of the population-based Italian Longitudinal Study on Aging, we examined 2410 older individuals in a longitudinal analysis with an 8-year follow-up. Biopsychosocial frailty operationalization was based on the results of a previous comprehensive geriatric assessment and the presence of physical frailty. Generalized estimating equation models assessed the independent contribution at three different follow-ups of baseline individuals with biopsychosocial frailty on occurring new events of myocardial infarction, PAD, and stroke. The prevalence of biopsychosocial frailty in older individuals with myocardial infarction was 10.9%, in older subjects with PAD was 8.9%, and in older individuals with definite stroke was 23.7%. After 8 years of follow-up, participants with biopsychosocial frailty showed an increased odds ratio (OR) of definite stroke [OR 2.67; 95% confidence interval 1.11-6.40]. No statistically significant associations between biopsychosocial frailty and myocardial infarction or PAD were observed. Over an 8-year follow-up, in a large, older cohort, a biopsychosocial frailty phenotype was associated with incident cerebrovascular disease, in particular with definite stroke. This complex phenotype of frailty has several modifiable components and could be an optimal target for potential interventions and prevention strategies.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8353-8365"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between backward walking speed and physical balance and fall risk in community-dwelling older adults.","authors":"Ziming Gong, Cen Chen, Lefei Wang, Ryuya Tanigawa, Eisei Harayama, Sitong Li, Hiro Kishimoto","doi":"10.1007/s11357-026-02149-3","DOIUrl":"10.1007/s11357-026-02149-3","url":null,"abstract":"<p><p>Backward walking is increasingly recognized as an alternative task for detecting balance deficits and fall risk in older adults. However, its utility as a functional indicator in healthy populations remains underexplored. This study aimed to investigate the potential associations between the backward walking speed (BWS), physical balance, and fall risk in community-dwelling older adults. In this cross-sectional study, 90 community-dwelling older adults were recruited. Self-selected backward walking speed (SBWS) was assessed together with the Berg Balance Scale (BBS), the Performance-Oriented Mobility Assessment (POMA), and the Fall Risk Index (FRI). Grip strength and cognitive function, evaluated using the Montreal Cognitive Assessment (MoCA), were also measured as covariates. Fear of backward walking (FoBW) was investigated using a self-administered questionnaire prior to the walking tests. Pearson correlation and multiple regression analyses were performed to examine the associations between SBWS, physical balance, and fall risk. The data of 84 participants (mean ± SD age 75.7 ± 5.0 years) were analyzed. Their mean forward and backward walking speeds were 1.36 ± 0.23 m/s and 0.73 ± 0.24 m/s, respectively. The SBWS showed moderate correlations with the Timed Up and Go (TUG) test (r = -0.52), forward speed (r = 0.49), and grip strength (r = 0.41), and weaker correlations with the BBS (r = 0.38), MoCA (r = 0.23) and FES-I (r = -0.34) . No statistically significant correlations were found between SBWS and POMA-Total (r = 0.20), FRI (r = 0.09). In adjusted regression models, SBWS was significantly associated with higher BBS scores (β = 3.744, p = 0.023) and lower TUG times (β = -1.488, p = 0.029) but not with the POMA-Total (β = 1.052, p = 0.344) or FRI (β = 3.001, p = 0.096). BWS may serve as a multidimensional indicator of physical and psychological vulnerability in older adults. Longitudinal studies with dynamic or dual-task assessments are necessary to validate its predictive value for fall risk screening.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"8531-8544"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multilevel regulation of skeletal muscle ferroptosis in aging: sex- and exercise-dependent effects on histological, molecular, and genetic markers.","authors":"Fujue Ji, Hyeonseung Rheem, Haesung Lee, Minyeong Eom, Jong-Hee Kim","doi":"10.1007/s11357-025-02073-y","DOIUrl":"10.1007/s11357-025-02073-y","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent form of regulated cell death, is increasingly recognized as a key contributor to aging-associated skeletal muscle degeneration and dysfunction. However, the interactive effects of aging, sex, and exercise modality on ferroptosis regulatory markers at the histological, protein, and gene expression levels remain poorly understood. Male (n = 23) and female (n = 23) mice aged 7 (young) and 17 (aged) months were assigned to sedentary control, voluntary wheel running, or forced treadmill exercise. Ferroptosis in the quadriceps muscle was assessed using histological markers (e.g., fibrosis, Fe³⁺ accumulation, 4-HNE, MDA), protein-level markers (e.g., GPX4, SLC7A11, p-AMPK, MDA, GSH/GSSG), and gene expression markers (e.g., SLC7A11, GSS, ACSL4, POR). Aging significantly elevated histological indicators of ferroptosis-fibrosis, lipid peroxidation, and iron overload-regardless of sex. At the protein and gene levels, sex-dependent differences were evident: aged females exhibited lower MDA and GSSG levels and upregulation of antioxidant-related genes, compared with aged males. Both exercise interventions modulated ferroptosis markers, with forced exercise exerting more pronounced effects than voluntary exercise. Notably, aged females demonstrated the most substantial reductions in ferroptosis-related markers in response to forced exercise, indicating a significant sex-by-exercise interaction. Aging markedly increases ferroptosis-related changes in skeletal muscle, with partial sex-specific differences at the molecular level. Forced exercise provides more robust regulatory effect against ferroptosis than voluntary exercise, especially in aged females. These findings underscore the therapeutic potential of sex-specific, targeted exercise interventions for mitigating ferroptosis-mediated muscle deterioration during aging.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"7823-7845"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145943281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}