Zhengqi Wei,Keke Wei,Ming Ying,Shanna Meng,Jingjing Li,Junqing Sun,Lei Zhang,Na Wang
{"title":"The Influence of Air Pollution on Cognitive Function in Middle-aged and Older Population: The Role of Healthy Lifestyle and Socioeconomic Factors.","authors":"Zhengqi Wei,Keke Wei,Ming Ying,Shanna Meng,Jingjing Li,Junqing Sun,Lei Zhang,Na Wang","doi":"10.1093/gerona/glaf167","DOIUrl":"https://doi.org/10.1093/gerona/glaf167","url":null,"abstract":"BACKGROUNDAir pollution is a potentially modifiable risk factor for Cognitive impairment (CoI). Therefore, it is necessary to explore factors that can mitigate the impact of air pollution on the cognitive function of middle-aged and older population (MAOP).METHODSTo investigate the impact of single and combined exposure to air pollutants on the cognitive abilities of MAOP, and to explore the role of healthy lifestyle (HL) and socioeconomic factors, the Generalized Linear Model, Weighted Quantile Sum Regression model, and Restricted Cubic Splines model were jointly applied to explore the impact of air pollutant exposure on the cognitive abilities of the MAOP. Causal mediation effect model and moderation effect models are used to investigate the roles of HL, medical and health level (MHL), and digital economy (DE).RESULTSWe found that both single and mixed exposures to air pollutants (excluding O3) lead to a decline in cognitive function in the MAOP. Improvements in HL, MHL, and DE result in increased cognitive scores and reduced CoI risk in the MAOP, and all can mitigate the negative impact of air pollution on cognitive function. HL has a significant mediating effect in the relationship between air pollutant exposure and cognitive function in the MAOP.CONCLUSIONIncreased exposure to air pollutants is associated with a decline in cognitive abilities and an increased CoI risk in the MAOP. HL, MHL and DE could alleviate the adverse effects of air pollution on cognitive function in the MAOP.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693461","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}
Phoebe Imms,Nikhil N Chaudhari,Daniel Cummings,Daniel Eid Rodriguez,Guiseppe Barisano,Paul L Hooper,M Katherine Sayre,Edmond Seabright,Randall C Thompson,M Linda Sutherland,James D Sutherland,Benjamin C Trumble,Michael Gurven,Jonathan Stieglitz,Caleb E Finch,Hillard S Kaplan,Wendy J Mack,Margaret Gatz,Andrei Irimia
{"title":"Physical activity mediates age differences in cognition among Tsimane forager-horticulturalists.","authors":"Phoebe Imms,Nikhil N Chaudhari,Daniel Cummings,Daniel Eid Rodriguez,Guiseppe Barisano,Paul L Hooper,M Katherine Sayre,Edmond Seabright,Randall C Thompson,M Linda Sutherland,James D Sutherland,Benjamin C Trumble,Michael Gurven,Jonathan Stieglitz,Caleb E Finch,Hillard S Kaplan,Wendy J Mack,Margaret Gatz,Andrei Irimia","doi":"10.1093/gerona/glaf163","DOIUrl":"https://doi.org/10.1093/gerona/glaf163","url":null,"abstract":"BACKGROUNDThe Tsimane and Moseten of the Bolivian Amazon are highly physically active and exhibit low rates of cognitive impairment and brain atrophy.METHODSWe use structural equation modelling to examine how their physical activity levels mediate the relationship between a) age and cognition, and b) age and cognition via brain volume (BV).RESULTSTsimane males (n = 305, mean ± SD age = 59.94 ± 9.68) and Tsimane females (n = 265, mean ± SD age = 59.28 ± 9.79) exhibit significantly higher levels of physical activity than Moseten males (n = 106, mean ± SD age = 58.15 ± 9.93) and Moseten females (n = 96, mean ± SD age = 56.63 ± 9.69). Physical activity significantly mediates the relationship between age and cognition in Tsimane males (indirect effect estimate β = -0.01, p < .01) and Tsimane females (indirect effect estimate β = -0.04, p = .01), but not in Moseten males or females.CONCLUSIONSAmong Tsimane males, who are more physically active than Tsimane females, the association between age and cognition via BV is significantly mediated by physical activity. Among Tsimane females, mediation occurs directly via physical activity, bypassing BV. These results suggest that mechanisms of cognitive differences across ages differ by sex and population. Studying the relationship between brain atrophy and lifestyle in non-industrialized populations elucidates biological and environmental correlates of brain health.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693491","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}
Qiaofeng Ye, Aaliya Ahamed, Idan Shalev, Laura Etzel
{"title":"Evaluation of reproductive profiles, epigenetic aging, and mortality in post-menopausal women","authors":"Qiaofeng Ye, Aaliya Ahamed, Idan Shalev, Laura Etzel","doi":"10.1093/gerona/glaf166","DOIUrl":"https://doi.org/10.1093/gerona/glaf166","url":null,"abstract":"Evolutionary theories of aging indicate trade-offs between reproduction and longevity. Epigenetic clocks, such as PhenoAge, GrimAge, and DunedinPoAm, were designed to reflect biological age and be used as surrogates for mortality and healthspan. The current study investigated the connection between reproductive profiles, epigenetic aging and mortality among post-menopausal women (50-85 years) with data from the National Health and Nutrition Examination Survey across the United States (N = 770). Using latent profile analysis, we identified four distinct reproductive profiles: high gravidity but average parity (Class 1); high gravidity and parity (Class 2); premature menopause (Class 3); an average profile (Class 4). Women of Class 3 had an accelerated pace of aging as indicated by DunedinPoAm, but not an older epigenetic age as measured by PhenoAge or GrimAge. The association was significant among women who had ever used female hormones (β = 0.521; 95%CI 0.014-1.027). Women of Class 1 or 2 did not exhibit accelerated epigenetic aging. Women of Class 3 had higher mortality (HR = 1.40, 95%CI 1.08-1.81), and 36.3% of the effect was mediated through accelerated DunedinPoAm. Findings suggest that women with reproductive profiles characterized by premature menopause may have altered epigenetic aging trajectories. Pace of aging may be more sensitive to the impact of reproductive profile variations than the status of biological age as indicated by PhenoAge or GrimAge. Clinically monitoring the pace of biological aging among women with premature menopause and an appropriate application of hormone replacement therapy may minimize the negative consequence of accelerated biological aging and reduce premature mortality.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685049","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":"Determinants of mobility in community-dwelling older adults: a network analysis before, during and two years after the onset of the COVID-19 pandemic.","authors":"Katja Lindeman,Taina Rantanen,Essi-Mari Tuomola,Johanna Eronen,Laura Karavirta,Kaisa Koivunen","doi":"10.1093/gerona/glaf162","DOIUrl":"https://doi.org/10.1093/gerona/glaf162","url":null,"abstract":"BACKGROUNDWe conceptualized out-of-home mobility as life space mobility and autonomy outdoors. Both are correlated with quality of life and influenced by multiple underlying factors. We used a complex systems approach and network models to explore changes in networks consisting of out-of-home mobility indicators and their determinants before, during and two years after the onset of the COVID-19 pandemic.METHODSParticipants were older adults aged 75, 80 and 85 years at baseline (2017-2018), with follow-ups in 2020 and 2021-2022 (n = 607). Life-space mobility, autonomy outdoors, and socio-demographic, physical, psychosocial, financial, and environmental determinants were assessed using the same validated scales at all three time points. Mixed graphical model networks were estimated for each time point. Differences in network properties and the relative importance of determinants associated with life-space mobility and autonomy outdoors were compared across time points.RESULTSDuring the COVID-19 pandemic, both life-space mobility and autonomy outdoors declined (p < 0.05). Throughout the follow-up, walking difficulty and sex remained consistently associated with life-space mobility and psychosocial factors with autonomy outdoors. At the onset of the pandemic, being female (vs. male) was more strongly associated with reduced autonomy outdoors than at other times, while the associations with older age and poorer health were weaker.CONCLUSIONSThe pandemic reduced older adults' out-of-home mobility and altered the factors underlying it. During the pandemic, environmental support for out-of-home mobility diminished as destinations of interest for older people were closed. This especially affected women, potentially leading to less favorable participation trajectories in the future.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684145","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}
Atsumu Yuki, Yukiko Nishita, Akinori Nakamura, Takashi Kato, Chikako Tange, Shu Zhang, Fujiko Ando, Hiroshi Shimokata, Rei Otsuka
{"title":"Longitudinal Relationships between Daily Activity and Hippocampal Atrophy in Japanese Dwellers","authors":"Atsumu Yuki, Yukiko Nishita, Akinori Nakamura, Takashi Kato, Chikako Tange, Shu Zhang, Fujiko Ando, Hiroshi Shimokata, Rei Otsuka","doi":"10.1093/gerona/glaf155","DOIUrl":"https://doi.org/10.1093/gerona/glaf155","url":null,"abstract":"Background The relationship between physical activity and hippocampal volume is important; however, most studies have used questionnaires to measure physical activity. We aimed to determine whether maintaining high levels of daily physical activity measured by an accelerometer reduces hippocampal atrophy in community-dwelling adults. Methods This cohort study used data from community-dwelling adults aged ≥60 years who participated in the National Institute for Longevity Sciences Longitudinal Study of Aging, which is a population-based prospective cohort study of approximately 2,300 Japanese adults. Tertiles of step count, light-intensity physical activity, and moderate-to-vigorous-intensity physical activity (MVPA) were measured using accelerometers. Changes in the hippocampal and total grey matter volumes over approximately 10 years were obtained from high-resolution 3D T1-weighted Magnetic Resonance Imaging (MRI) images. Results The analysis included 287 men and 264 women, with no history of head surgery, dementia, or stroke at baseline, who completed the MRI scans and follow-up surveys. Significant interactions between MVPA and years since baseline with whole and right hippocampal volumes were observed only in men (p&lt;.05). Annual whole hippocampal atrophy volumes in the lowest, intermediate, and highest MVPA groups were -72.11, -58.25, and -59.53 mm3, respectively. Right hippocampal atrophy volumes were -36.93, -28.47, and -28.53 mm3, respectively. The total and right hippocampal volumes in the lowest MVPA group declined more rapidly than those in the other groups. Conclusions Lower MVPA levels in men were associated with higher rates of both total and right hippocampal atrophy. The relationship between MVPA and atrophy may help develop dementia prevention strategies.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"209 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677632","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}
Xinyi Han,Congcong Pan,Zhichong Cai,Ao Zhang,Ni Zhong,Liyuan Pu,Meifen Wu,Liyuan Han,Haiyan Pan
{"title":"The association between sensory function changes, metabolic and inflammatory biomarkers, and cognitive impairment: two prospective cohort studies.","authors":"Xinyi Han,Congcong Pan,Zhichong Cai,Ao Zhang,Ni Zhong,Liyuan Pu,Meifen Wu,Liyuan Han,Haiyan Pan","doi":"10.1093/gerona/glaf160","DOIUrl":"https://doi.org/10.1093/gerona/glaf160","url":null,"abstract":"BACKGROUNDRecent findings indicate a correlation between sensory impairment and cognitive impairment, while earlier research primarily focused on baseline sensory function without addressing its progression. This research examines the association between dynamic changes in visual impairment (VI), hearing impairment (HI), and dual sensory impairment (DSI) with cognitive impairment, concurrently evaluating the mediating role of biomarkers.METHODSThis research employed cohort data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018) and the Health and Retirement Study (HRS, 2010-2018). Changes in sensory function were evaluated using initial and second follow-up datasets, with participants categorized into no SI, new-onset, remitted, and persistent. The quantification of cognitive impairment risk utilized multivariable-adjusted Cox proportional hazards regression models. Mendelian randomization (MR) was applied to infer genetic causality, while mediation analysis was performed to assess the influence of metabolic and inflammatory biomarkers.RESULTSThis study analyzed data from CHARLS (N = 5,224) and HRS (N = 8,314), revealing that new-onset HI and DSI were significantly associated with an increased risk of cognitive impairment (CHARLS, HR 1.25-1.93; HRS, HR 1.05-1.67). Conversely, remitted HI or DSI was associated with a reduced risk (CHARLS, HR 0.62-0.95), particularly among individuals aged below 65. MR analyses confirmed a causal relationship between hearing loss and cognition, with high-density lipoprotein cholesterol and cystatin C demonstrating partial mediation effects.CONCLUSIONSCognitive health strategies should incorporate regular screening and early intervention for sensory impairments (HI/DSI) among middle-aged and older populations.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678111","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":"Accelerometer-Measured Multi-dimensional Physical Activity Patterns and Physical Functional Decline: A Prospective National Cohort Study of Aging.","authors":"Lingjie Fan,Junhan Zhao,Jian Wang,Xin Zhou Be,Xiyue Wang,Shengyi Liu,Fengyi Wang,Quan Wei,Tao Lin","doi":"10.1093/gerona/glaf158","DOIUrl":"https://doi.org/10.1093/gerona/glaf158","url":null,"abstract":"BACKGROUND: Physical activity (PA) is crucial for maintaining physical function in older adults, but relationships between multidimensional PA patterns and functional decline remain unclear. This study examined associations between accelerometer-measured PA patterns and physical function decline in older adults.METHODS: We conducted a prospective cohort study with one-year follow-up using data from 586 community-dwelling participants aged ≥65 years in the National Health and Aging Trends Study (2021-2022). Wrist-worn accelerometers measured four PA dimensions: cumulative (total activity counts), peak (maximum intensity), temporal (active and sedentary minutes), and fragmentation. Physical function decline was defined as any decrease in Short Physical Performance Battery score at follow-up. Multivariable logistic regression examined associations between PA dimensions and physical function changes.RESULTS: Higher total activity counts (OR: 0.71, 95% CI: 0.59-0.85), minutes spent active (OR: 0.75, 95% CI: 0.63-0.89), and maximum intensity (OR: 0.67, 95% CI: 0.55-0.83) were associated with lower odds of functional decline, while activity fragmentation showed the opposite relationship (OR: 1.23, 95% CI: 1.03-1.47). Dose-response analyses demonstrated continuous linear relationships. Compared to the lowest activity levels (10th percentile), participants at the 90th percentile showed substantially lower risk: total activity counts (OR: 0.50, 95% CI: 0.29-0.88), active minutes (OR: 0.58, 95% CI: 0.37-0.95), and maximum intensity (OR: 0.54, 95% CI: 0.32-0.75), while activity fragmentation showed progressive risk increase (OR: 1.37, 95% CI: 0.83-2.21). Domain-specific analyses showed consistent patterns.CONCLUSIONS: Multidimensional PA patterns have distinct relationships with functional decline in older adults. Findings support tailored PA recommendations and potential for targeted interventions.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661841","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":"Using Machine-Learning to Identify Differences in the Association between Blood-Based Biomarkers and Later Life Health Across Race and Ethnicity.","authors":"Mateo P Farina,Eric T Klopack,Eileen M Crimmins","doi":"10.1093/gerona/glaf153","DOIUrl":"https://doi.org/10.1093/gerona/glaf153","url":null,"abstract":"Increasingly, biomarkers are used to understand health and health inequalities among older adults. Combined with advancements in machine-learning approaches, researchers are using predictive algorithms of later life health to identify biomarkers of interest and create biological risk scores. However, these algorithms may select biomarkers that are most important for majority populations, which, in most population-based samples, would reflect the health and aging of White older adults. Understanding how biomarker selection varies across race/ethnicity across different types of health outcomes is paramount to advancing GeroScience research. We used the 2016 Venous Blood Substudy (VBS) of the Health and Retirement Study (HRS). We fit race-stratified boosted decision tree models to predict all-cause mortality, multimorbidity, diabetes, and heart conditions from 54 biomarkers in the 2016 VBS that covered 11 biological systems. We, then, graphed biomarkers that had feature values above .01 for each algorithm to show racial/ethnic differences in biomarker selection. We found more variation in biomarker selection across racial/ethnic groups for all-cause mortality. We found little variation in biomarker selection for heart conditions and diabetes. There was some variation for multimorbidity but with substantial overlap across racial/ethnic groups. While machine-learning approaches for developing biological risk scores and identifying biomarkers linked to later life health will yield additional insight into aging processes in human populations, researchers must consider how these approaches may differ across race/ethnicity for different types of health conditions and its potential implications for Geroscience research.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661840","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}
Ilja Demuth,Valentin Max Vetter,Jan Homann,Marit Philine Junge,Vera Regitz-Zagrosek,Denis Gerstorf,Christina M Lill,Lars Bertram
{"title":"DunedinPACE Predicts Incident Metabolic Syndrome: Cross-sectional and Longitudinal Data from the Berlin Aging Study II (BASE-II).","authors":"Ilja Demuth,Valentin Max Vetter,Jan Homann,Marit Philine Junge,Vera Regitz-Zagrosek,Denis Gerstorf,Christina M Lill,Lars Bertram","doi":"10.1093/gerona/glaf157","DOIUrl":"https://doi.org/10.1093/gerona/glaf157","url":null,"abstract":"BACKGROUNDAim of the study was a comparative analysis of different epigenetic clocks with regard to their ability to predict a future onset of the Metabolic Syndrome (MetS). In addition, cross-sectional relationships between epigenetic age measures and MetS were investigated.METHODSMetS was diagnosed in participants of the Berlin Aging Study II at baseline (n = 1,671, mean age 68.8 ± 3.7 years, 51.6% women) and at follow-up (n = 1,083; 7.4 ± 1.5 years later). DNA methylation age acceleration (DNAmAA) was calculated for a total of ten epigenetic clocks at baseline. In addition, DunedinPACE, a DNAm-based measure of the pace of aging, was calculated. The relationship between MetS, DNAmAA and DunedinPACE was investigated by fitting regression models adjusted for potential confounders and calculating receiver operating characteristic statistics.RESULTSAmong all biomarkers investigated, DunedinPACE was the only DNAm-based predictor that was significantly associated with incident MetS at follow-up on average 7.4 years later (OR: 9.84, p = 0.028). Logistic regression models predicting MetS that either included solely clinical parameters or solely epigenetic clock estimates (DNAmAA) or DunedinPACE revealed that GrimAge DNAmAA had an area under the curve most comparable to the model considering clinical variables only. Cross-sectional differences between participants with and without MetS remained statistically significant for DunedinPACE only after covariate adjustment (baseline: β = 0.042, follow-up: β = 0.031, p < 0.0001 in both cases).CONCLUSIONComparison of epigenetic clocks in relation to MetS showed strong and consistent associations with DunedinPACE. Our results highlight the potential of using certain DNAm-based measures of biological ageing in predicting the onset of clinical outcomes, such as MetS.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661839","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}
Niko Paavo Tynkkynen,Kaisa Koivunen,Päivi Herranen,Laura Joensuu,Timo Törmäkangas,Elina Sillanpää
{"title":"The Association of a Polygenic Lifespan Score With the Risk of Common Age-Related Diseases and Mortality.","authors":"Niko Paavo Tynkkynen,Kaisa Koivunen,Päivi Herranen,Laura Joensuu,Timo Törmäkangas,Elina Sillanpää","doi":"10.1093/gerona/glaf156","DOIUrl":"https://doi.org/10.1093/gerona/glaf156","url":null,"abstract":"BACKGROUNDAging increases the risk of major noncommunicable diseases. Research into the genetics of health-related traits could reveal genetic pathways for robustness against these diseases. We studied how a genetic predisposition for a long lifespan is associated with the risk of all-cause mortality and major age-related noncommunicable diseases.METHODSWe analyzed data from 376 753 participants (mean age = 58.5 years; standard deviation = 13.9 years; 46.3% men) to examine how a polygenic lifespan score (PLS) is associated with the risk of all-cause mortality and major noncommunicable diseases. The associations between all-cause mortality, cancers, femur fracture, dementia, Alzheimer's disease, Parkinson's disease, type 2 diabetes, obesity, cardiovascular diseases, hypertension, ischemic heart diseases, coronary heart disease, stroke, and myocardial infarction were investigated using conventional and time-dependent Cox regression.RESULTSThe PLS was associated with all the above-mentioned outcomes except for Parkinson's disease. Most of the associations were time-dependent, and the hazard ratio (HR) varied over time from protective to risk-increasing. However, the current PLS predicted noncommunicable disease risks with small effect sizes (lowest HR ≈ 0.70, highest HR ≈ 1.20, Cox-Snell pseudo-R2 > 0.01).CONCLUSIONSGenetic predisposition for a longer lifespan was associated with a smaller risk of common age-related noncommunicable diseases suggesting greater robustness against these conditions. The lowest risks were found during periods when the incidences of diseases were greatest. The observed small effects highlight the need to better understand how accumulated environmental factors modify individual lifespans.","PeriodicalId":22892,"journal":{"name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661844","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}