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Background Measures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality. Methods We studied 63- to 76-year-old women (N = 395) from the Finnish Twin Study on Aging (FITSA). Participants’ biological age (epigenetic clocks DNAm GrimAge and DunedinPACE) was estimated using blood DNAm data. Tests of physical functioning conducted under standardized laboratory conditions included the Timed Up and Go (TUG) test and 10-m walk test. Mortality hazard ratios (HRs) were calculated per every one standard deviation (SD) increase in the predictor. Cox regression models were conducted for individuals and twin pairs, the latter controlling for underlying genetic effects. The models were adjusted for known lifestyle predictors of mortality. Results During the follow-up period (mean 17.0 years, range 0.2–20.3), 187 participants died. In both the individual-based and pairwise analyses, GrimAge and both functional biomarkers of aging were associated with mortality independent of family relatedness, chronological age, physical activity, body mass index, smoking, education, or chronic diseases. In a model including both the DNAm-based measures and functional biomarkers of aging, GrimAge and TUG remained predictive. Conclusions The findings suggest that DNAm GrimAge and the TUG test are strong predictors of mortality independent of each other’s and genetic influences. DNAm-based measures and functional tests capture different aspects of the aging process and thus complement each other as measures of biological aging in predicting mortality. peerReviewed

Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations, monozygotic (MZ) twin pairs discordant for health habits provide an interesting natural experiment. Twin pairs discordant for leisure-time physical activity (LTPA) in early adult life is thus a powerful study design to investigate the associations between long-term LTPA and indicators of health and wellbeing. We have identified 17 LTPA discordant twin pairs from two Finnish twin cohorts and summarize key findings of these studies in this paper. The carefully characterized rare long-term LTPA discordant MZ twin pairs have participated in multi-dimensional clinical examinations. Key findings highlight that compared with less active twins in such MZ twin pairs, the twins with higher long-term LTPA have higher physical fitness, reduced body fat, reduced visceral fat, reduced liver fat, increased lumen diameters of conduit arteries to the lower limbs, increased bone mineral density in loaded bone areas, and an increased number of large high-density lipoprotein particles. The findings increase our understanding on the possible site-specific and system-level effects of long-term LTPA.

Objective Physical activity (PA) is associated with a decreased incidence of dementia, but much of the evidence comes from short follow-ups prone to reverse causation. This meta-analysis investigates the effect of study length on the association. Design A systematic review and meta-analysis. Pooled effect sizes, dose-response analysis and funnel plots were used to synthesise the results. Data sources CINAHL (last search 19 October 2021), PsycInfo, Scopus, PubMed, Web of Science (21 October 2021) and SPORTDiscus (26 October 2021). Eligibility criteria Studies of adults with a prospective follow-up of at least 1 year, a valid cognitive measure or cohort in mid-life at baseline and an estimate of the association between baseline PA and follow-up all-cause dementia, Alzheimer's disease or vascular dementia were included (n=58). Results PA was associated with a decreased risk of all-cause dementia (pooled relative risk 0.80, 95% CI 0.77 to 0.84, n=257 983), Alzheimer's disease (0.86, 95% CI 0.80 to 0.93, n=128 261) and vascular dementia (0.79, 95% CI 0.66 to 0.95, n=33 870), even in longer follow-ups (>= 20 years) for all-cause dementia and Alzheimer's disease. Neither baseline age, follow-up length nor study quality significantly moderated the associations. Dose-response meta-analyses revealed significant linear, spline and quadratic trends within estimates for all-cause dementia incidence, but only a significant spline trend for Alzheimer's disease. Funnel plots showed possible publication bias for all-cause dementia and Alzheimer's disease. Conclusion PA was associated with lower incidence of all-cause dementia and Alzheimer's disease, even in longer follow-ups, supporting PA as a modifiable protective lifestyle factor, even after reducing the effects of reverse causation.

Introduction: High physical activity (PA) at old age indicates good functional capacity enabling independent living. We investigated how different disease conditions are associated with measured PA indicators in old women and men, and whether they recognize this association. Materials and methods: This cross-sectional twin cohort study in Finland comprised 779 individuals (276 complete twin pairs, including 117 monozygotic pairs), who participated in hip-worn accelerometer monitoring of PA and responded to questions on diseases and mobility limitations at mean age of 73 (range 71–75). Results: Of the participants, 23.2% reported having a disease restricting mobility. With sex and age in the regression model, the reported disease restricting mobility explained 11.8% of the variation in moderate-to-vigorous PA (MVPA) and 10.4% of the variation in daily steps. Adding stepwise other self-reported diseases and body mass index to the model increased the explanatory power for MVPA up to 18.5% and 25.5%, and for daily steps up to 16.0% and 20.7%, respectively. In the co-twin control analysis the PA differences were smaller in disease-discordant monozygotic than dizygotic pairs. Conclusions: Chronic disease conditions are associated with low PA, which individuals may not always recognize. Shared genetic factors may explain part of the associations.Key messagesAmong community-dwelling older men and women one-fourth of the variation in objectively measured moderate-to-vigorous physical activity is accounted for by age, sex, body mass index and self-reported diseases.Occurrence of chronic diseases is associated with low physical activity and individuals do not always recognize this.Healthcare professionals should pay attention to the low physical activity and mobility of individuals with chronic disease conditions before these result in limitations in independent living. Among community-dwelling older men and women one-fourth of the variation in objectively measured moderate-to-vigorous physical activity is accounted for by age, sex, body mass index and self-reported diseases. Occurrence of chronic diseases is associated with low physical activity and individuals do not always recognize this. Healthcare professionals should pay attention to the low physical activity and mobility of individuals with chronic disease conditions before these result in limitations in independent living.