Three-year lifestyle changes, genetic risk, and risk of frailty among older adults: A national community-based cohort...

The association between change in lifestyle in late-life and frailty mediated by genetic risk is yet to be elucidated. This study aimed to investigate the associations of change in lifestyle in late-life and genetic risk with frailty among older adults.

6945 participants aged 65 or older were included from the Chinese Longitudinal Healthy Longevity Survey. Three-year lifestyle changes were assessed by comparing the first survey (2002, 2005, 2008, 2011) with the second survey (2005, 2008, 2011, 2014), evaluating changes in overall lifestyle scores, lifestyle combinations, and four factors (smoking, alcohol use, physical activity, and diet). A weighted polygenic risk score was constructed using 25 frailty-associated Single Nucleotide Polymorphism in a subsample of 4346 participants. Frailty was defined as a frailty index ≥0.25. Cox proportional hazards regression models, with age as the time scale and stratified by 5-year age groups, were used to estimate the interaction between genetic and lifestyle factors on frailty risk.

During a median follow-up time of 5.7 years [interquartile range (IQR): 3.1-8.9), 2525 participants developed frailty. Compared to consistently unhealthy lifestyles, the hazard ratios (HRs) for frailty were 0.64 [95 % confidence interval (CI): 0.54-0.75] for healthy-to-healthy, 0.80 (95 % CI: 0.68-0.93) for moderate-to-moderate, and 0.83 (95 % CI: 0.70-0.99) for moderate-to-healthy changes. Participants with a high genetic risk group suffered from 87 % (95%CI: 1.68-2.08) higher risk of frailty. Notably, the highest frailty risk was observed in individuals with high genetic risk who changed from a healthy to an unhealthy lifestyle (HR: 2.86, 95%CI: 1.89-4.34).

Improving or maintaining a healthy lifestyle over three years, even in late life, was associated with a lower risk of frailty. This underscores the importance of a healthy lifestyle in preventing frailty, particularly for individuals with a high genetic risk.