Epigenetic age acceleration and the risk of frailty, and persistent activities of daily living (ADL) disability.

BACKGROUND: Epigenetic ageing is among the most promising ageing biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study investigated whether epigenetic age acceleration (AA) is associated with the change in frailty scores over 7 years and the 7-year risk of incident frailty and persistent Activities of Daily Living (ADL) disability among 560 Australians (50.7% females) aged ≥70 years. METHODS: Seven AA indices, including GrimAge, GrimAge2, FitAge and DunedinPACE, were estimated from baseline peripheral-blood DNA-methylation. Frailty was assessed using both the 67-item deficit-accumulation frailty index (FI) and Fried phenotype (Fried). Persistent ADL disability was defined as loss of ability to perform one or more basic ADLs for at least 6 months. Linear mixed models and Cox proportional-hazard regression models were used as appropriate. RESULTS: Accelerated GrimAge, GrimAge2, FitAge and DunedinPACE at baseline were associated with increasing FI scores per year (adjusted-Beta ranged from 0.0015 to 0.0021, P < 0.05), and accelerated GrimAge and GrimAge2 were associated with an increased risk of incident FI-defined frailty (adjusted-HRs 1.43 and 1.39, respectively, P < 0.05). The association between DunedinPACE and the change in FI scores was stronger in females (adjusted-Beta 0.0029, P 0.001 than in males (adjusted-Beta 0.0002, P 0.81). DunedinPACE, but not the other AA measures, was also associated with worsening Fried scores (adjusted-Beta 0.0175, P 0.04). No associations were observed with persistent ADL disability. CONCLUSION: Epigenetic AA in later life is associated with increasing frailty scores per year and the risk of incident FI-defined frailty.

Gender-specific aspects of socialisation and risk of cardiovascular disease among community-dwelling older adults: a prospective cohort study using machine learning algorithms and a conventional method.

BACKGROUND: Gender influences cardiovascular disease (CVD) through norms, social relations, roles and behaviours. This study identified gender-specific aspects of socialisation associated with CVD. METHODS: A longitudinal study was conducted, involving 9936 (5,231 women and 4705 men) initially healthy, community-dwelling Australians aged 70 years or more from the ASPirin in Reducing Events in the Elderly (ASPREE) study and ASPREE Longitudinal Study of Older Persons, with a median follow-up time of 6.4 years. Variable categorisation, variable selection (using machine learning (ML) models; Elastic Net and extreme gradient boosting) and Cox-regression were employed separately by binary gender to identity socialisation factors (n=25 considered) associated with CVD. RESULTS: Different socialisation factors were identified using the ML models. In the Cox model, for both genders, being married/partnered was associated with a reduced risk of CVD (men: HR 0.76, 95% CI 0.60 to 0.96; women: HR 0.67, 95% CI 0.58 to 0.95). For men, having 3-8 relatives they felt close to and could call on for help (HR 0.76, 95% CI 0.58 to 0.99; reference <3 relatives), having 3-8 relatives they felt at ease talking with about private matters (HR 0.70, 95% CI 0.55 to 0.90; reference <3 relatives) or playing games such as chess or cards (HR 0.82, 95% CI 0.67 to 1.00) was associated with reduced risk of CVD. For women, living with others (HR 0.71, 95% CI 0.55 to 0.91) or having ≥3 friends they felt at ease talking with about private matters (HR 0.74, 95% CI 0.58 to 0.95; reference <3 friends) was associated with a lower risk of CVD. CONCLUSIONS: This study demonstrates the need to prioritise gender-specific social factors to improve cardiovascular health in older adults.