Healthy lifestyle in late-life, longevity genes, and life expectancy among older adults: a 20-year, population-based, prospective cohort study

Background Lifestyle and longevity genes have different and important roles in the human lifespan; however, the association between a healthy lifestyle in late-life and life expectancy mediated by genetic risk is yet to be elucidated. We aimed to investigate the associations of healthy lifestyle in late-life and genetic risk with life expectancy among older adults. Methods A weighted healthy lifestyle score was constructed from the following variables: current non-smoking, non-harmful alcohol consumption, regular physical activity, and a healthy diet. Participants were recruited from the Chinese Longitudinal Healthy Longevity Survey, a prospective community-based cohort study that took place between 1998 and 2018. Eligible participants were aged 65 years and older with available information on lifestyle factors at baseline, and then were categorised into unhealthy (bottom tertile of the weighted healthy lifestyle score), intermediate (middle tertile), and healthy (top tertile) lifestyle groups. A genetic risk score was constructed based on 11 lifespan loci among 9633 participants, divided by the median and classified into low and high genetic risk groups. Stratified Cox proportional hazard regression was used to estimate the interaction between genetic and lifestyle factors on all-cause mortality risk. Findings Between Jan 13, 1998, and Dec 31, 2018, 36 164 adults aged 65 years and older were recruited, among whom a total of 27 462 deaths were documented during a median follow-up of 3.12 years (IQR 1.62-5.94) and included in the lifestyle association analysis. Compared with the unhealthy lifestyle category, participants in the healthy lifestyle group had a lower all-cause mortality risk (hazard ratio [HR] 0.56 [95% CI 0.54-0.57]; p<0.0001). The highest mortality risk was observed in individuals in the high genetic risk and unhealthy lifestyle group (HR 1.80 [95% CI 1.63-1.98]; p<0.0001). The absolute risk reduction was greater for participants in the high genetic risk group. A healthy lifestyle was associated with a gain of 3.84 years (95% CI 3.05-4.64) at the age of 65 years in the low genetic risk group, and 4.35 years (3.70-5.06) in the high genetic risk group. Interpretation A healthy lifestyle, even in late-life, was associated with lower mortality risk and longer life expectancy among Chinese older adults, highlighting the importance of a healthy lifestyle in extending the lifespan, especially for individuals with high genetic risk. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.