Experimental gerontology最新文献

{"title":"Gender disparities in marital status and risk of developing age acceleration: Findings from NHANES 2015-2018.","authors":"Jialu Wang, Feixiang Xu, Yin Wang, Lizhan Bie","doi":"10.1016/j.exger.2025.112912","DOIUrl":"10.1016/j.exger.2025.112912","url":null,"abstract":"<p><strong>Background: </strong>Marriage has been a hot topic since ancient times forever, yet there is little research evidence on marital status as an important socio-behavioral factor in relation to aging. Our study aimed to investigate the association between marital status and the risk of age acceleration, as well as exploring whether there were gender differences in this association.</p><p><strong>Methods: </strong>This cross-sectional study involved 3202 participants from four National Health and Nutrition Examination Survey (NHANES) cycles between 2015-2018. Marital status was collected via a questionnaire. Phenotypic Age Acceleration (PhenoAgeAccel) was calculated by performing a linear regression of PhenoAge against chronological age.</p><p><strong>Results: </strong>The multivariable logistic regression model showed that, compared to individuals who were married or living with a partner, those who were widowed, divorced or separated were associated with a 35 % reduced risk of PhenoAgeAccel development (OR: 0.65, 95 % CI: 0.49-0.87), while those who had never been married had a 1.79-fold increased risk of PhenoAgeAccel development (OR: 1.79, 95 % CI: 1.33-2.40). Of these, individuals who were married or living with a partner, or who were widowed, divorced or separated, and who did not have depression, had a lower risk of aging compared with people who were married or living with a partner and who had depression (OR: 0.61, 95 % CI: 0.38-0.98; OR:0.41, 95 % CI: 0.23-0.73, respectively). Gender disparity analyses indicated that never being married increased the risk of PhenoAgeAccel in men (OR: 2.45, 95 % CI: 1.69-3.56) while it decreased the risk in women (OR: 0.56, 95 % CI: 0.39-0.81) (P for interaction = 0.013).</p><p><strong>Conclusions: </strong>The findings of this cross-sectional study suggested that differential marital status has a variable impact on the risk of developing age acceleration, with significant gender differences. All indications are that men benefit more from marriage in the aging process, which is food for thought.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"112912"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of non-exercise estimated cardiorespiratory fitness with mortality risk in individuals with diabetic kidney diseases: Analysis of 1999-2018 NHANES data.","authors":"Xiaoxu Ge, Juan Du, Jiajia Wang, Liuqing Xi, Wenfang Peng, Shan Huang, Ying Xie","doi":"10.1016/j.exger.2025.112856","DOIUrl":"10.1016/j.exger.2025.112856","url":null,"abstract":"<p><strong>Objective: </strong>Although non-exercise estimated cardiorespiratory fitness (eCRF) algorithms correlate well with measured CRF, their prognostic value in high-risk populations remains unclear. We investigated the associations between eCRF and mortality risk in adults with diabetic kidney disease (DKD), a vulnerable population with elevated mortality risk.</p><p><strong>Methods: </strong>Data from adults with DKD were derived from the 1999-2018 National Health and Nutrition Examination Survey. The primary exposure was eCRF, which was calculated from validated algorithm incorporating age, sex, body mass index, waist circumference, resting heart rate, physical activity, and smoking status. The primary outcomes were all-cause and cardiovascular disease (CVD) mortality. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were calculated from Cox proportional hazards models for the associations between eCRF and mortality risk.</p><p><strong>Results: </strong>Among 2045 participants (mean age 61.65 years, 52.10 % men) included, 804 (35.84 %) deaths occurred during a median follow-up of 84 months, of which 296 were from CVD causes. Compared with the highest eCRF quartile, the HRs (95 % CIs) of the lowest quartile were 1.75 (1.27-2.40) for all-cause mortality and 2.29 (1.32-3.99) for CVD mortality. Restricted cubic spline curves demonstrated inversely linear relationships between eCRF and all-cause and CVD mortality. Associations between eCRF and all-cause mortality were stronger in female participants, those with overweight or obesity, and those without prior CVD.</p><p><strong>Conclusions: </strong>Lower eCRF was independently associated with elevated risks of all-cause and CVD mortality in individuals with DKD, supporting the utility of eCRF as a practical prognostic tool in clinical management of DKD.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"112856"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial dysfunction drives cellular senescence: Molecular mechanisms of inter-organelle communication","authors":"Ziyue Xie ,&nbsp;Xinyu Zhang ,&nbsp;Yu Li ,&nbsp;Ruigong Zhu","doi":"10.1016/j.exger.2025.112913","DOIUrl":"10.1016/j.exger.2025.112913","url":null,"abstract":"<div><div>Mitochondrial dysfunction is a central driver of cellular senescence, a core hallmark of aging. While intrinsic mechanisms have been extensively reviewed, this article offers a novel paradigm by emphasizing the critical role of interorganellar communication in mitochondria-mediated senescence. We present a systematic dissection of the molecular mechanisms underlying functional crosstalk between mitochondria and key organelles, including the endoplasmic reticulum (ER), lysosomes, and peroxisomes. A particular focus is placed on established regulatory hubs such as mitochondria-associated ER membranes (MAMs), which orchestrate calcium signaling, lipid metabolism, and inflammatory responses. We further explore emerging pathways involving lysosomal mitochondrial coordination in nutrient sensing and mitophagy, and peroxisomal mitochondrial cooperation in redox balance and lipid homeostasis. By elucidating how defects in these dynamic networks propagate mitochondrial damage and execute senescence, this review establishes a unified framework for aging as integrated organelle network dysfunction. This synthesis advances fundamental aging biology and identifies novel molecular targets, providing a foundation for developing therapeutic strategies targeting organelle networks against age related pathologies.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"211 ","pages":"Article 112913"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145222263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular senescence in skeletal diseases: A bibliometric analysis from 2007 to 2024.","authors":"Xuanrui Zhang, Biao Yang, Xunpei Xu, Zhanrong Zhang, Zhengbo Tao, Weijin Zhang, Zheng Zhang, Xuhui Zhou","doi":"10.1016/j.exger.2025.112857","DOIUrl":"10.1016/j.exger.2025.112857","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence is a state of permanent cell cycle arrest. Numerous studies have highlighted the significant role of cellular senescence in age-related skeletal diseases, including intervertebral disc degeneration (IDD), osteoporosis, and osteoarthritis (OA). This article aims to review the current research landscape and identify emerging trends.</p><p><strong>Methods: </strong>Literature concerning cellular senescence and skeletal disease was obtained from the Web of Science Core Collection database, covering publications from 2007 to 2024. The Bibliometrix R package, VOSviewer, and CiteSpace were employed to perform the bibliometric analysis.</p><p><strong>Results: </strong>A total of 2653 publications were analyzed, revealing a rapid growth trend. China emerged as the dominant contributor, with the highest publication volume (n = 1148), while the United States led in citation impact (total citations = 50,420). Key journals, such as Osteoarthritis and Cartilage and Aging Cell, served as primary platforms for high-impact studies. The most influential author was James L. Kirkland, followed by Richard F. Loeser. Keyword clustering identified cellular senescence in intervertebral disc degeneration, osteoporosis, and osteoarthritis as core research domains, while current frontiers focus on the senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, extracellular vesicles, and immune infiltration.</p><p><strong>Conclusion: </strong>Research in this field has garnered substantial attention in recent years. This bibliometric analysis not only underscores the correlation between cellular senescence and skeletal diseases, but also highlights that targeting cellular senescence and the SASP may offer potential therapeutic strategies. These findings can inform future research directions and the development of targeted interventions for age-related skeletal conditions.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"112857"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic changes in nutritional status and sleep disturbance in Parkinson's disease.","authors":"Bingchuan Xie, Junqiang Bao, Lizhuang Zhang, Zhenguo Wu, Hongmin Zhao","doi":"10.1016/j.exger.2025.112855","DOIUrl":"10.1016/j.exger.2025.112855","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate the relationship between dynamic changes in nutritional status and sleep disturbance in patients with Parkinson's disease (PD).</p><p><strong>Methods: </strong>This study included 209 PD patients with regular follow-ups from January 2021 to January 2023. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Data on nutritional indicators, including albumin, hemoglobin, total protein, cholesterol, triglyceride, LDL cholesterol, prealbumin, transferrin, NEFA, and retinol-binding protein (RBP), were collected at both admission and discharge. Patients were categorized into groups based on changes in albumin levels, and the relationship between nutritional status and sleep disturbance was analyzed.</p><p><strong>Results: </strong>The study found that 27.75 % of patients experienced malnutrition, while 48.33 % had sleep disturbance. Before treatment, BMI, MDS-UPDRS, albumin, hemoglobin, total protein, cholesterol, triglyceride, transferrin, NEFA, and RBP were positively associated with sleep disturbance (r = 5.012, 6.821, 3.291, 0.782, 0.674, 0.813, 0.938, 0.531, 0.763, 0.362, P < 0.001); age, LDL cholesterol, and prealbumin were negatively correlated (r = -2.182, -2.187, -9.761, P < 0.001). Multivariate logistic regression analysis identified prealbumin as a significant risk factor for sleep disturbance (OR: 1.384, 95 % CI: 1.062-1.883, P < 0.05).</p><p><strong>Conclusions: </strong>The study concluded that nutritional status, particularly levels of albumin and prealbumin, is closely related to the occurrence of sleep disturbance in PD patients.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"112855"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gait and sensory parameters based machine learning classification for detecting cognitive impairment in older adults.","authors":"Emilija Kostic, Kiyoung Kwak, Shinyoung Lee, Dongwook Kim","doi":"10.1016/j.exger.2025.112915","DOIUrl":"https://doi.org/10.1016/j.exger.2025.112915","url":null,"abstract":"<p><p>Detecting mild cognitive impairment in its early stages can increase access to treatment and allow care planning. However, it is still challenging as many older adults do not preemptively seek a neuropsychological assessment. To address this issue, methods for detecting cognitive impairment without cognitive testing should be explored. The present study designed machine learning algorithms based solely on gait and sensory parameters and assessed their ability to discern older individuals with suspected cognitive impairment from those with healthy cognition. Community-dwelling men older than sixty-five (n = 94) underwent cognitive, sensory, and gait function assessments. Based on the cognitive evaluation, they were divided into the non-cognitively impaired group (n = 65) and the suspected impaired cognition group (n = 29). Machine learning models were trained and compared in terms of diagnostic accuracy to discern the group suspected of having cognitive impairment from the non-cognitively impaired group. Among the machine learning algorithms, a support vector machine and an automated machine learning model showed the highest ability in classifying older individuals with suspected cognitive impairment from those with healthy cognition with an accuracy of 82.8 %. The gait and hearing parameters of older individuals with suspected cognitive impairment differed significantly from those of cognitively healthy older adults. By utilizing these parameters, the present research presented the possibility of developing a fast and simple screening method for detecting early cognitive impairment without needing neuropsychological testing.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"112915"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do older adults with and without a history of falls show different gait patterns in response to individualized treadmill perturbations?","authors":"Michel Hackbarth, Tania Zieschang, Sandra Lau, Jessica Koschate-Storm","doi":"10.1016/j.exger.2025.112853","DOIUrl":"10.1016/j.exger.2025.112853","url":null,"abstract":"<p><strong>Background: </strong>Dynamic reactive balance is key to avoid falls during walking and can be challenged with treadmill-based gait perturbations. The use of mechanical gait perturbations to measure reactive dynamic balance performance, is discussed to identify individuals at risk of falling. Gait speed and perturbation intensity, are often standardized in study populations. In heterogeneous study populations, this entails the risk of either overburdening the participants or failing to adequately challenge them.</p><p><strong>Research question: </strong>Are gait parameters and compensatory steps, after mechanical treadmill-based perturbations using perturbation intensities at the individual single step threshold and preferred walking speed, different between younger and older adults with or without a history of falling?</p><p><strong>Methods: </strong>In this study, 86 younger and older adults with and without a history of falls completed two treadmill-walking trials with mediolateral and anteposterior perturbations. Step length and step width were analyzed before and after perturbations using ANOVA with repeated measures.</p><p><strong>Results: </strong>The adjustments of both parameters to individualized mediolateral perturbations differed between younger and older participants, while between older adults with and without a history of falls, only small differences in step width (p < 0.001, η_p² = 0.141) were observed.</p><p><strong>Significance: </strong>Individually tailored treadmill-perturbations can be safely applied in older adults. Compensatory steps as a reaction to perturbations differ between younger and older adults. However, at the individual limit of balance control, differences between older adults with and without a history of falls are small.</p>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":" ","pages":"112853"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of senescent fibroblasts secretome in ovarian cancer dissemination","authors":"Luce Perié ,&nbsp;Alexandra Landras ,&nbsp;Mickaëla Bignard ,&nbsp;Marion Theuret ,&nbsp;Mélanie Briand ,&nbsp;Franck Carreiras ,&nbsp;Cédric R. Picot","doi":"10.1016/j.exger.2025.112909","DOIUrl":"10.1016/j.exger.2025.112909","url":null,"abstract":"<div><div>Aging is a significant risk factor in ovarian cancers, which remains one of the most lethal gynecological malignancies. Over 50 % of ovarian cancer cases occur in women aged 65 and older. During aging, senescent cells progressively accumulate in various tissues, contributing to structural and inflammatory changes in the tumor microenvironment. While recent studies have underscored the role of the senescent mesothelial cells in facilitating cancer cell dissemination, the contribution of senescent fibroblasts that are a major component of the connective tissue, remains elusive. In this study, we first characterized the senescent phenotype of human ovarian fibroblasts, with a focus on extracellular matrix (ECM) remodeling and the senescence-associated secretory phenotype (SASP). Senescent ovarian fibroblasts exhibited an accumulation of intracellular Fibronectin (Fn), impaired fibrillar Fn into ECM assembly, and marked alterations in ECM organization. SASP profiling revealed a pro-inflammatory secretome enriched in immune-modulatory cytokines and factors potentially involved in cancer cell dissemination and metastasis. We then evaluated the influence of the senescent fibroblast secretome on ovarian cancer cell behavior. While it did not alter cancer cell proliferation, it conferred resistance to apoptosis and significantly enhanced cancer cell migration and invasion. Altogether, our findings highlight the role of senescent ovarian fibroblasts in promoting cancer cell dissemination and suggest that age-related stromal changes contribute to disease progression.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"211 ","pages":"Article 112909"},"PeriodicalIF":4.3,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of a multicomponent training programme for older adults with decreased functional capacity: An economic evaluation","authors":"J. Subías-Perié ,&nbsp;D. Navarrete-Villanueva ,&nbsp;A.I. Fernández-García ,&nbsp;A. Moradell ,&nbsp;J.T. Alcalá-Nalvaiz ,&nbsp;E.J. Groessl ,&nbsp;I. Ara ,&nbsp;S. Vila-Maldonado ,&nbsp;J. Pérez-Gómez ,&nbsp;M. Gonzalez-Gross ,&nbsp;A. Gómez-Cabello ,&nbsp;G. Vicente-Rodríguez ,&nbsp;J.A. Casajús","doi":"10.1016/j.exger.2025.112911","DOIUrl":"10.1016/j.exger.2025.112911","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to (I) examine the resources required to implement a multicomponent training (MCT) programme, (II) assess its impact on health care utilisation cost, and (III) evaluate its cost-effectiveness in older adults with decreased functional capacity.</div></div><div><h3>Methods</h3><div>A total of 123 older adults (mean age: 80.3 ± 5.9 years) were allocated into a control (CON, <em>n</em> = 64) or training group (TRAIN, <em>n</em> = 59). The TRAIN group performed a 6-month MCT programme, which included aerobic exercise, resistance training, flexibility and balance components, while the CON group continued with their usual care. Functional capacity, frailty and health-related quality of life (HRQoL) were assessed at three different timepoints using the Short Physical Performance Battery (SPPB), Frailty Phenotype of Fried and the EuroQol-5D (EQ-5D), respectively. Primary outcome measures included the costs of delivering the MCT, health care utilisation, quality-adjusted life-years (QALYs), and the incremental cost effectiveness ratio (ICER). Analyses were conducted from a health system perspective with a 6-month time horizon.</div></div><div><h3>Results</h3><div>While no significant changes were observed in the CON group, the TRAIN group showed improvements in SPPB (+3.38 ± 1.32), HRQoL (+0.07 ± 0.12), and frailty (−0.64 ± 1.06) (all <em>p</em> &lt; 0.05). The average cost per TRAIN participant was €164. Health care utilisation cost was lower for TRAIN compared to CON (€3091 and €4135, respectively). The ICERs were €115/point increase in SPPB and €407/point reduction in frailty score. The cost per QALY gained by the TRAIN participant relative to the usual care cost was €6274. At a willingness-to-pay threshold of €49,000/QALY (Spanish Health System), the probability of the exercise intervention being cost-effective was 100 %.</div></div><div><h3>Conclusions</h3><div>The 6-month Exernet-Elder 3.0 training programme demonstrated an ICER of €115 per SPPB point gained, €407 per point of frailty reduction, and €6274 per QALY gained. The intervention was low-cost (€164 per participant) and produced clinically meaningful improvements in functional capacity, HRQoL, and frailty. These findings underscore the importance of integrating a structured, group-based exercise programmes into public health strategies to address the growing socioeconomic and health burden associated with ageing populations.</div></div><div><h3>Trial registration</h3><div>ClinicalTrial.gov identifier: NCT03831841</div></div><div><h3>Date of registration</h3><div>6/02/2019 (Last update 02/07/2020).</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"211 ","pages":"Article 112911"},"PeriodicalIF":4.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory mechanisms of transforming growth factor-β in senescence of fibroblast associated with refractory skin diseases","authors":"Yujie Zheng ,&nbsp;Jindi Lei ,&nbsp;An Zhang ,&nbsp;Cheng Cao ,&nbsp;Aie Xu ,&nbsp;Miaoni Zhou ,&nbsp;Fuquan Lin","doi":"10.1016/j.exger.2025.112900","DOIUrl":"10.1016/j.exger.2025.112900","url":null,"abstract":"<div><div>Fibroblasts, critical for skin structure and function via extracellular matrix (ECM) production, undergo senescence linked to ECM changes and inflammation via senescence-associated secretory phenotypes (SASPs). Transforming growth factor (TGF-β), a pleiotropic cytokine, modulates fibroblast function through multiple signaling pathways, inducing cell cycle arrest, oxidative stress, DNA damage, and SASP production. These processes disrupt ECM homeostasis, exacerbate inflammation, and impair tissue repair, contributing to pathological skin changes.</div><div>TGF-β induced fibroblast senescence involves multiple mechanisms and pathways. It causes cell cycle arrest by upregulating CDK inhibitors and activating the p53 pathway. TGF-β also promotes oxidative stress-induced senescence by increasing reactive oxygen species (ROS) production, activating pathways like SMAD, and causing DNA damage. In photoaging, UV exposure induces fibroblast senescence via TGF-β related mechanisms, reducing collagen production and increasing MMP levels. TGF-β also suppresses immune cell functions, creating an immunosuppressive microenvironment that accelerates cellular senescence.</div><div>In refractory skin diseases like vitiligo, melanoma, and so on, TGF-β plays a complex role. Its abnormal activation drives fibroblast senescence, impacting immune responses and skin structure. However, Maintaining the normal expression of TGF-β preserves ECM homeostasis, promotes collagen synthesis, and reduces inflammatory factor expression. Emerging therapeutic strategies targeting TGF-β signaling show promise. Pharmaceutical agents and phototherapy mitigate senescence by modulating TGF-β pathways and thus suppress ROS, enhancing collagen synthesis. Combined approaches synergistically improve skin repair and elasticity.</div><div>In summary, TGF-β significantly regulates fibroblast senescence in refractory skin diseases through various mechanisms and pathways. Its precise modulation could enhance skin repair and anti-aging therapies. However, further research is needed to explore the interactions between anti-aging ingredients and their clinical effects.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"211 ","pages":"Article 112900"},"PeriodicalIF":4.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182428","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}