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Background DNA methylation-derived epigenetic clocks and frailty are well-established biological age measures capturing different aging processes. However, whether they are dynamically linked to each other across chronological age remains poorly understood. Methods This analysis included 1 309 repeated measurements in 524 individuals aged 50–90 years from the Swedish Adoption/Twin Study of Aging. Frailty was measured using a validated 42-item frailty index (FI). Five epigenetic clocks were calculated, including 4 principal component (PC)-based clocks trained on chronological age (PCHorvathAge and PCHannumAge) and aging-related physiological conditions (PCPhenoAge and PCGrimAge), and a pace of aging clock (DunedinPACE). Using dual change score models, we examined the dynamic, bidirectional associations between each of the epigenetic clocks and the FI over age to test for potential causal associations. Results The FI exhibited a nonlinear, accelerated increase across the older adulthood, whereas the epigenetic clocks mostly increased linearly with age. For PCHorvathAge, PCHannumAge, PCPhenoAge, and PCGrimAge, their associations with the FI were primarily due to correlated levels at age 50 but with no evidence of a dynamic longitudinal association. In contrast, we observed a unidirectional association between DunedinPACE and the FI, where a higher DunedinPACE predicted a subsequent increase in the FI, but not vice versa. Conclusions Our results highlight a temporal order between epigenetic aging and frailty such that changes in DunedinPACE precede changes in the FI. This potentially suggests that the pace of aging clock can be used as an early marker of the overall physiological decline at system level. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Dementia predicts increased mortality. We used case‐control and co‐twin control models to investigate genetic and shared environmental influences on this association. METHODS: Case‐control design, including 987 twins with dementia and 2938 age‐ and sex‐matched controls in the Swedish Twin Registry. Co‐twin control design, including 90 monozygotic (MZ) and 288 dizygotic (DZ) twin pairs discordant for dementia. To test for genetic and environmental confounding, differences were examined in mortality risk between twins with dementia and their matched or co‐twin controls. RESULTS: Twins with dementia showed greater mortality risk than age‐ and sex‐matched controls (HR = 2.02 [1.86, 2.18]). Mortality risk is significantly elevated but attenuated substantially in discordant twin pairs, for example, comparing MZ twins with dementia to their co‐twin controls (HR = 1.48 [1.08, 2.04]). DISCUSSION: Findings suggest that genetic factors partially confound the association between dementia and mortality and provide an alternative hypothesis to increased mortality due to dementia itself. Highlights: We studied dementia and mortality in twin pairs discordant for dementia.People without dementia outlived people with dementia.Identical twins with dementia and their co‐twin controls had similar survival time.Findings suggest genotype may explain the link between dementia and mortality. [ABSTRACT FROM AUTHOR]

Objectives The educational gradient in late-life health is well established. Despite this, there are still ambiguities concerning the role of underlying confounding by genetic influences and gene-environment (GE) interplay. Here, we investigate the role of educational factors (attained and genetic propensities) on health and mortality in late life using genetic propensity for educational attainment (as measured by a genome-wide polygenic score, PGSEdu) and attained education. Methods By utilizing genetically informative twin data from the Swedish Twin Registry (n = 14,570), we investigated influences of the educational measures, familial confounding as well as the possible presence of passive GE correlation on both objective and subjective indicators of late-life health, that is, the Frailty Index, Multimorbidity, Self-rated health, cardiovascular disease, and all-cause mortality. Results Using between-within models to adjust for shared familial factors, we found that the relationship between educational level and health and mortality later in life persisted despite controlling for familial confounding. PGSEdu and attained education both uniquely predicted late-life health and mortality, even when mutually adjusted. Between-within models of PGSEdu on the health outcomes in dizygotic twins showed weak evidence for passive GE correlation (prGE) in the education-health relationship. Discussion Both genetic propensity to education and attained education are (partly) independently associated with health in late life. These results lend further support for a causal education-health relationship but also raise the importance of genetic contributions and GE interplay. [ABSTRACT FROM AUTHOR]

Aims Materials and Methods Results Conclusions About 10%–30% of individuals with obesity are metabolically healthy, but the specific characteristics of the metabolically healthy obesity (MHO) phenotype remain unclear. We aimed to examine how physical activity, education, depressive symptoms and genetic predisposition to obesity differ between individuals with MHO and those with metabolically unhealthy obesity (MUO), and whether these factors predict stability in MHO or conversion to a metabolically unhealthy state.We retrieved data on 9809 individuals with obesity from the Health and Retirement Study collected between 2006 and 2016. We compared how physical activity, education, depressive symptoms and a polygenic score for higher body mass index (BMI) (PGSBMI) differed cross‐sectionally between MHO and MUO using logistic regression. We then examined if the same factors predict conversion to a metabolically unhealthy state over 4 years in individuals with MHO.Individuals with MHO had higher physical activity (odds ratio [OR] = 0.81), higher education (OR = 0.83) and lower depressive symptoms (OR = 1.14) compared to those with MUO but did not differ in the PGSBMI. The associations were slightly attenuated in mutually adjusted models. None of the factors were associated with conversion from MHO to a metabolically unhealthy state. However, a higher PGSBMI indicated 24% lower risk of conversion to a metabolically unhealthy state (p = 0.07).Physical activity, education and depressive symptoms differed between MHO and MUO, even when mutually adjusted for, but did not predict conversion from a metabolically healthy to unhealthy state. Although not statistically significant, the results indicated that those with genetically predicted high BMI are more likely to maintain MHO and not convert to a metabolically unhealthy state. [ABSTRACT FROM AUTHOR]

Background: Psychological resilience refers to an individual's ability to cope with and adapt to challenging life circumstances and events., Objective: This study aims to explore the association between psychological resilience and all-cause mortality in a national cohort of US older adults by a cross-sectional study., Methods: The Health and Retirement Study (2006-2008) included 10 569 participants aged ≥50. Mortality outcomes were determined using records up to May 2021. Multivariable Cox proportional hazards models were used to analyse the associations between psychological resilience and all-cause mortality. Restricted cubic splines were applied to examine the association between psychological resilience and mortality risk., Findings: During the follow-up period, 3489 all-cause deaths were recorded. The analysis revealed an almost linear association between psychological resilience and mortality risk. Higher levels of psychological resilience were associated with a reduced risk of all-cause mortality in models adjusting for attained age, sex, race and body mass index (HR=0.750 per 1 SD increase in psychological resilience; 95% CI 0.726, 0.775). This association remained statistically significant after further adjustment for self-reported diabetes, heart disease, stroke, cancer and hypertension (HR=0.786; 95% CI 0.760, 0.813). The relationship persisted even after accounting for smoking and other health-related behaviours (HR=0.813; 95% CI 0.802, 0.860)., Conclusions: This cohort study highlights the association between psychological resilience and all-cause mortality in older adults in the USA., Clinical Implications: Psychological resilience emerges as a protective factor against mortality, emphasising its importance in maintaining health and well-being., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Dementia predicts increased mortality. We used case-control and co-twin control models to investigate genetic and shared environmental influences on this association., Methods: Case-control design, including 987 twins with dementia and 2938 age- and sex-matched controls in the Swedish Twin Registry. Co-twin control design, including 90 monozygotic (MZ) and 288 dizygotic (DZ) twin pairs discordant for dementia. To test for genetic and environmental confounding, differences were examined in mortality risk between twins with dementia and their matched or co-twin controls., Results: Twins with dementia showed greater mortality risk than age- and sex-matched controls (HR = 2.02 [1.86, 2.18]). Mortality risk is significantly elevated but attenuated substantially in discordant twin pairs, for example, comparing MZ twins with dementia to their co-twin controls (HR = 1.48 [1.08, 2.04])., Discussion: Findings suggest that genetic factors partially confound the association between dementia and mortality and provide an alternative hypothesis to increased mortality due to dementia itself. Highlights We studied dementia and mortality in twin pairs discordant for dementia. People without dementia outlived people with dementia. Identical twins with dementia and their co-twin controls had similar survival time. Findings suggest genotype may explain the link between dementia and mortality., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)