The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

{"title":"It's Never Too Early, It's Never Too Late: The Potential of Health Behaviors for Cardiovascular Health in Nonagenarians. Data From the Mugello Study.","authors":"Silvia Pancani, Gemma Lombardi, Francesco Sofi, Guido Pasquini, Federica Vannetti, Francesca Cecchi, Claudio Macchi","doi":"10.1093/gerona/glaf064","DOIUrl":"10.1093/gerona/glaf064","url":null,"abstract":"<p><strong>Background: </strong>The Life's Essential 8 (LE8) is a composite metric including 4 health behaviors (diet, physical activity, nicotine exposure, and sleep) and 4 health factors (body mass index, nonhigh-density lipoprotein cholesterol, blood glucose, and blood pressure). This study aimed to describe the cardiovascular health (CVH) metrics promoted by LE8 in nonagenarians and to investigate their relationship with mortality at 5 and 10 years.</p><p><strong>Methods: </strong>This study was conducted within the framework of the Mugello Study, a longitudinal survey on nonagenarians living in the Mugello area (Tuscany, Italy). One-hundred and fifty-seven subjects (42 males and 115 females, median age 92 years) were administered a series of validated questionnaires and underwent instrumental examinations and blood withdrawal. CVH metrics were calculated according to LE8 guidelines. Physical activity and sleep duration were quantitatively estimated using a monitor device.</p><p><strong>Results: </strong>In the male group, after 5 and 10 years of follow-up, a higher Health Behavior score was associated with a lower risk of all-cause mortality (HR: 0.963, p = .005 and HR: 0.972, p = .020; after 5 and 10 years). Differently, in the female group, no significant association was observed between the LE8 total score and subscores and different risk of mortality after 5 and 10 years from the interview.</p><p><strong>Conclusions: </strong>These findings highlight the importance of potentially modifiable behaviors in improving survival. They support resource investments to address the needs of individuals in this stage of life and encourage them to be empowered and actively engage in health-promoting behaviors.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702633","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":"Skeletal Muscle Aging: Lessons From Teleosts.","authors":"Tuyen K Quach, Megan F Taylor, Peter D Currie, Nir Eynon, Avnika A Ruparelia","doi":"10.1093/gerona/glae052","DOIUrl":"10.1093/gerona/glae052","url":null,"abstract":"<p><p>Aging is the greatest risk factor for a multitude of age-related diseases including sarcopenia-the loss of skeletal muscle mass and strength-which occurs at remarkable rates each year. There is an unmet need not only to understand the mechanisms that drive sarcopenia but also to identify novel therapeutic strategies. Given the ease and affordability of husbandry, along with advances in genomics, genome editing technologies, and imaging capabilities, teleost models are increasingly used for aging and sarcopenia research. Here, we explain how teleost species such as zebrafish, African turquoise killifish, and medaka recapitulate many of the classical hallmarks of sarcopenia, and discuss the various dietary, pharmacological, and genetic approaches that have been used in teleosts to understand the mechanistic basis of sarcopenia.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reciprocal Associations Between Trajectories of Physical Activity and Physical Function Among Older Women: Findings From the Australian Longitudinal Study on Women's Health.","authors":"Yuta Nemoto, Wendy J Brown, Geeske Peeters, Gregore Iven Mielke","doi":"10.1093/gerona/glaf059","DOIUrl":"10.1093/gerona/glaf059","url":null,"abstract":"<p><strong>Background: </strong>Although physical activity (PA) is known to improve physical function (PF), and functional decline impacts the capacity to engage in PA, the reciprocal relationship between PA and PF remains unclear.</p><p><strong>Methods: </strong>Data were from participants in the 1921-1926 cohort of the Australian Longitudinal Study on Women's Health (N = 8 238). PA and PF were assessed at 3-year intervals from 1999 (73-78 y) to 2011 (85-90 y). Group-based trajectory modeling was used to identify PA and PF trajectories, and associations between PA and PF were examined using mixed-effects models and restricted cubic spline modeling.</p><p><strong>Results: </strong>Three trajectories for PA and PF were identified: Low, Moderate, and High. Women in the High PA group maintained high PF and did not reach the starting PF level of the Low PA group (at age 73) until they were 87. Similarly, women in the High PF group maintained higher PA than those in the other groups. Women in the Low PF group never met PA guidelines and had PF scores below the disability threshold throughout the study. Restricted cubic splines showed that higher PA was associated with better PF 3 years later, and vice versa, indicating that PA and PF influence each other.</p><p><strong>Conclusion: </strong>There are reciprocal relationships between PF and PA; higher levels of PA promote better PF, and higher PF may help slow the decline in PA. Although rates of decline in PF show little variation with PA in women during their 80s, habitually high PA confers considerable benefits, contributing to additional years of healthy life.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Associated Increase in AT1R Expression in Human Testis and Its Intervention Effects on Leydig Cell Senescence in Aged Rodents.","authors":"Minye Zhao, Jinhua Wei, Yao Geng, Yang Zhang, Jie Zhao, Hong Yang, Wei Hua, Wei Li","doi":"10.1093/gerona/glaf004","DOIUrl":"10.1093/gerona/glaf004","url":null,"abstract":"<p><p>The active peptide hormone angiotensin II (Ang II) mediates the vast majority of the renin-angiotensin system action, mainly through activation of Ang II type-1 receptor (AT1R). AT1R expression peaks in newborn males and decreases toward the adult age, and it is shown to exhibit an inhibitory effect on human chorionic gonadotropin-stimulated steroidogenesis in Leydig cells (LCs), as well as a promoting effect on smooth muscle and endothelial cell senescence. However, whether hyperactivation of the AT1R signaling exerts any effects on LC senescence, which could provide insights into hypogonadism mechanisms for aging males, remains unexplored. We herein reported that AT1R expression was significantly upregulated in aged human and rat testes. Transgenic overexpression of AT1R in LCs mimicked multiple late-onset hypogonadism phenotypes, including acceleration of LC senescence, defective steroidogenesis and spermatogenesis, and increased inflammation and oxidative stress. One of the core biochemical events underpinning AT1R action was the AT1R-induced enhancement of the interaction between murine double minute 2 and the p65 subunit of nuclear factor-kappa B, consequently augmenting polyubiquitination and activation of p65, in a p38-dependent manner. Conversely, repression of AT1R activity ameliorated LC senescence and rescued testicular steroidogenesis in old rats. Together, forced expression of AT1R within the testicular interstitium potentiates aging-related traits in LCs, thereby leading to fertility impairment with defective steroidogenesis and spermatogenesis in male rodents. Our systematic analysis also indicates that blocking the Ang II/AT1R signal might be beneficial in intervening in disorders of late-onset hypogonadism in old males.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677435","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":"Advanced Glycation End-Products and Metabolomics Are Independently Associated With Frailty: The Longitudinal Doetinchem Cohort Study.","authors":"Lieke M Kuiper, H Susan J Picavet, M Liset Rietman, Martijn E T Dollé, W M Monique Verschuren","doi":"10.1093/gerona/glae272","DOIUrl":"10.1093/gerona/glae272","url":null,"abstract":"<p><p>Skin autofluorescence (SAF), reflecting advanced glycation endproducts' accumulation in tissue, has been proposed as a noninvasive aging biomarker. Yet, SAF has not been compared with well-established blood-based aging biomarkers such as MetaboHealth in association with frailty. Furthermore, no previous study determined the longitudinal association of SAF with frailty. We used 2 382 Doetinchem Cohort Study participants' (aged 46.0-85.4) cross-sectional data, of whom 1 654 had longitudinal SAF measurements. SAF was measured using the AGE Reader. MetaboHealth was calculated on 1H-NMR-metabolomics. Linear regressions were used for the associations of SAF and MetaboHealth on the 36-deficit frailty index and logistic regressions for being pre-frail or frail as determined by the frailty phenotype. Longitudinal associations were determined by an interaction term between age and SAF in a linear mixed model. SAF and MetaboHealth were associated with higher odds of pre-frailty (odd ratios per standard deviation SAF: 1.21 [1.10-1.32], MetaboHealth: 1.35 [1.24-1.49]) and frailty (SAF: 1.70 [1.41-2.06], MetaboHealth: 1.90 [1.57-2.32]). When mutually adjusted, both aging biomarkers remained associated with pre-frailty (SAF: 1.16 [1.05-1.27], MetaboHealth 1.33 [1.21-1.46]) and frailty (SAF: 1.52 [1.25-1.85], MetaboHealth: 1.75 [1.43-2.14]). Additionally, SAF and MetaboHealth were associated with higher frailty index scores (percentage increase per standard deviation SAF: 1.35 [1.00-1.70], MetaboHealth: 1.87 [1.54-2.20]), also after mutual adjustment (SAF: 1.02 [0.68-1.37], MetaboHealth: 1.69 [1.35-2.02]). SAF was also longitudinally associated with the frailty index (percentage per unit/year increase: 0.12 [0.07-0.16]). The mutual independence of SAF and MetaboHealth implies they capture distinct aspects of the aging process. Altogether, these findings emphasize SAF's clinical potential as an age-related decline biomarker, which could be further enhanced when combined with MetaboHealth.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testosterone Concentration and Incident Depression in Older Men: A Longitudinal Cohort Study.","authors":"Malcolm Forbes, Mojtaba Lotfaliany, Cammie Tran, Mohammadreza Mohebbi, Robyn L Woods, John J McNeil, Michael Berk","doi":"10.1093/gerona/glaf019","DOIUrl":"10.1093/gerona/glaf019","url":null,"abstract":"<p><strong>Background: </strong>Testosterone has been implicated in mood regulation, yet its role in the development and treatment of depression remains unclear. This study investigated the association between testosterone concentrations and the incidence of depression in older men.</p><p><strong>Methods: </strong>We utilized data from 4 107 men aged 70 years and older who participated in the Aspirin in Reducing Events in the Elderly (ASPREE) and ASPREE-XT studies. Serum total testosterone concentrations were measured at baseline and year 3. Depressive symptoms were assessed annually using the CES-D-10 scale, with incident depression defined as a CES-D-10 score of ≥8. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) for incident depression, adjusted for potential confounders.</p><p><strong>Results: </strong>During a median follow-up of 8.4 years, 1 449 participants experienced an episode of depression. Baseline total testosterone concentrations were not significantly associated with the risk of incident depression, whether treated as continuous variables (HR 1.00, 95% CI 0.99-1.01) or when categorized into quintiles. Similarly, changes in testosterone concentrations from baseline to year 3 did not predict incident depression (aHR 1.03, 95% CI 0.99-1.08). A subgroup analysis focusing on men with biochemical evidence of hypogonadism also found no association with incident depression.</p><p><strong>Conclusions: </strong>Our findings do not support an association between testosterone concentrations and the risk of developing depression in older men. These results suggest that testosterone is not an important factor in the pathogenesis of depression in this population. There may still be individual variability in response to testosterone changes and its potential impact on mood disorders.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality Trends in Pre-COVID-19 and COVID-19 Eras Among Oldest Veterans.","authors":"Jessica Palmer, Maithri Kondapaka, Brock A Beamer, Tariq Siddiqui, John D Sorkin, Wilbur H Chen, Raya Elfadel Kheirbek","doi":"10.1093/gerona/glaf051","DOIUrl":"10.1093/gerona/glaf051","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic has had a profound impact on older adults, particularly those with existing comorbidities. To inform targeted healthcare strategies for this heterogeneous group, this study seeks to analyze and compare mortality trends among various geriatric age groups within the Veterans Affairs healthcare system, both during the COVID-19 era and the pre-COVID era, while accounting for demographic and clinical factors such as age, gender, race, and comorbidities.</p><p><strong>Methods: </strong>In this retrospective cohort study using Veterans Affairs Informatics and Computing Infrastructure data, two samples were analyzed: Veterans alive during the pre-COVID era (January 2019-December 2019) and during the COVID era (January 2020-December 2020). Propensity score matching was used to control for age, sex, race, body mass index, and comorbidities.</p><p><strong>Results: </strong>The primary outcome was mortality. Odds ratios (ORs) and 95% confidence intervals were calculated to compare mortality across age groups. Unmatched analyses, adjusted for age, sex, race, body mass index, and comorbidities, showed that mortality significantly increased during the COVID era for age groups 70-79 (OR 1.38), 80-89 (OR 1.14), and 90-99 (OR 1.20), all with p values < 0.0001. No significant increase was observed in centenarians (OR 1.10, 95% confidence interval 0.90-1.35, p = .345). Matched analysis confirmed these findings.</p><p><strong>Conclusions: </strong>In a large cohort of older Veterans, COVID-19 had a significant impact on mortality in older adults aged 70-99, highlighting the need for targeted public health interventions. The lack of significant increase in mortality for centenarians is notable and warrants further study to identify possible protective factors in this unique population.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association of Circulating Immune Cells With Cognitive Function, Brain Imaging, and Incident All-cause and Alzheimer's Dementia: The Framingham Offspring Study.","authors":"Yumeng Cao, Lindsay R Salvati, Jiachen Chen, Ahmed Ragab, Jesse Mez, Claudia L Satizabal, Michael L Alosco, Yuan Fang, Wei Qiao Qiu, Kathryn L Lunetta, Joanne M Murabito, Margaret F Doyle","doi":"10.1093/gerona/glaf067","DOIUrl":"10.1093/gerona/glaf067","url":null,"abstract":"<p><p>Emerging evidence supports the central role of the immune system in brain health, yet little is known about the role of circulating immune cells and cognitive function or brain health in dementia-free populations. We investigated the association of 43 immune cells with cognitive function, structural brain imaging, and incident dementia in Framingham Heart Study Offspring participants. Immune cells were phenotyped by flow cytometry. Linear mixed effects models were used for cross-sectional associations between immune cells and 4 cognitive domain scores and 13 brain magnetic resonance imaging measurements. Cox proportional hazards regression models tested the relationship between immune cells and time to dementia. Models were adjusted for age, sex, education, cytomegalovirus status, and APOE genotype, with further adjustment for cardiovascular risk factors. Data was further stratified by cytomegalovirus status. Among 795 participants with cellular phenotyping, cognitive testing and brain imaging data (mean age 61, 52% women), there were no associations between immune cells and cognitive test scores. Several significant associations between immune cells and regional brain magnetic resonance imaging measurements were observed. Higher CD8+ cells [CD8+CD45RO-CCR7-CD27- (Teff), CD8+CD45RA+CD28-CD57+(TEMRA), CD8+CD27-CD28-] associated with greater cerebrum gray and frontal gray matter volumes and inclusion of cardiovascular risk factors strengthened the association. Among CMV+ participants, CD8+TEMRA and CD8+Teff cells were significantly associated with higher total gray and frontal gray matter volumes. No significant associations were observed between immune cells and incident all-cause or Alzheimer's disease dementia. The pathobiology underpinning the associations between immune cells and brain volumes require further study and validation in diverse samples.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Association Between Multimorbidity, Participating Activity, and Cognitive Function: Cross-lagged Mediation Analysis.","authors":"Shuojia Wang, Zikuan Yang, Yilin Chen, Jing Zhu, Lin Kang, Lixin Cheng","doi":"10.1093/gerona/glaf062","DOIUrl":"10.1093/gerona/glaf062","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have reported an association between multimorbidity and cognitive function; however, the specific direction and underlying mechanism remain unclear. The study aimed to explore the direction of this association and to examine the role of physical activity and leisure activity among older adults.</p><p><strong>Methods: </strong>Data from 5 546 dementia-free Americans aged 60 or above of 2008 (T1) and 2016 (T2) of the Health and Retirement Study were used. Multimorbidity was measured by the multimorbidity weight index. Cognitive function was measured by the Telephone Interview of Cognitive Status. We used cross-lagged panel models to determine the associations between multimorbidity and cognitive function and examine the mediation effect of physical and leisure activity.</p><p><strong>Results: </strong>There was a bidirectional association between multimorbidity and cognitive function. More severe multimorbidity predicted worse cognitive function (β = -0.064, SE = 0.016) and vice versa (β = -0.024, SE = 0.009). Paths from multimorbidity to cognitive function were stronger than those from cognitive function to multimorbidity. Physical and leisure activity mediated the association between multimorbidity (T1) and cognitive function (T2), and the association between cognitive function (T1) and multimorbidity (T2). The bidirectional association between multimorbidity and cognitive function was only observed in APOE ε4 noncarriers.</p><p><strong>Conclusions: </strong>A negative bidirectional association was observed between multimorbidity and cognitive function. Additionally, the association is mediated by physical and leisure activity.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702634","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":"Frailty Mediated the Associations of Fine Particulate Matter With Depression and Anxiety: Findings From the UK Biobank.","authors":"Xiangying Suo, Junxi Zhang, Jing Guo, Yang Liu, Jie You, Quanjun Lyu, Yacong Bo","doi":"10.1093/gerona/glaf047","DOIUrl":"10.1093/gerona/glaf047","url":null,"abstract":"<p><strong>Background: </strong>The role of frailty in the associations of fine particulate matter (PM2.5) with depression and anxiety was unknown.</p><p><strong>Methods: </strong>This study is a longitudinal population-based cohort study. A total of 444 094 UK Biobank participants without depression or anxiety at baseline were included. PM2.5 concentrations and frailty phenotype were measured at baseline, while incident depression and anxiety were identified during a median follow-up of 7.8 y. A multivariable Cox regression model was utilized to evaluate the prospective relationships between PM2.5/frailty and the risk of depression and anxiety. Mediation analyses were performed to examine whether the associations were mediated by frailty.</p><p><strong>Results: </strong>Both frailty and PM2.5 exposure were associated with a higher risk of depression and anxiety. Each 10 μg/m3 increase in PM2.5 was associated with a 33% and 42% higher risk of depression (hazard ration [HR] 1.33, 95% CI: 1.17-1.49) and anxiety (HR 1.42, 95% CI: 1.24-1.67), respectively. Compared with individuals with nonfrailty, those with frailty was associated with a higher risk of depression (HR 3.14, 95% CI: 3.01-3.28) and anxiety (HR 2.39, 95% CI: 2.28-2.52), respectively. The estimate of the nature indirect effects of frailty was 1.07 (95% CI: 1.06-1.09) and 1.05 (95% CI: 1.05-1.06), which accounted for 64.6% and 22.4% of the associations between PM2.5 and depression/anxiety, respectively.</p><p><strong>Conclusions: </strong>Our findings suggest that both exposure to PM2.5 and frailty are associated with higher risk of depression and anxiety. The adverse associations between PM2.5 and depression/anxiety are partially mediated through frailty. Targeting frailty management could be a critical strategy for reducing the PM2.5-related psychiatric health burden.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569316","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}