Genetic predisposition, modifiable lifestyles, and their joint effects on human lifespan

A longitudinal cohort study investigated the associations across genetic and lifestyle factors with lifespan. Using UK Biobank data, 353 742 adults of European ancestry, were recruited from 2006 to 2010 and were followed up until 2021. Participants were grouped into three genetically determined lifespan categories including long (20.1%), intermediate (60.1%), and short (19.8%), and into three lifestyle score categories including favourable (23.1%), intermediate (55.6%), and unfavourable (21.3%).
With a median follow-up of 12.86 years, 24,239 deaths were identified. The hazard ratio (HR) of death for individuals with a genetic predisposition to a short lifespan was 1.21 (95% CI 1.16 to 1.26) compared to those with a genetic predisposition to a long lifespan. The HR of death for individuals in the unfavourable lifestyle category was 1.78 (95% CI 1.71 to 1.85), compared with those in the favourable lifestyle category. Participants with a genetic predisposition to a short lifespan and an unfavourable lifestyle had 2.04 times (95% CI 1.87 to 2.22) higher rates of death compared with those with a genetic predisposition to a long lifespan and a favourable lifestyle. No multiplicative interaction was detected between the polygenic risk score of lifespan and the weighted healthy lifestyle score. The optimal combination of healthy lifestyles, including never smoking, regular physical activity, adequate sleep duration, and a healthy diet, was derived to decrease risk of premature death (death before 75 years).
Genetic and lifestyle factors were independently associated with lifespan. Adherence to healthy lifestyles could largely attenuate the genetic risk of a shorter lifespan or premature death. The optimal combination of healthy lifestyles could convey better benefits for a longer lifespan, regardless of genetic background, the research concludes.
Source: Bian Z, Wang L, Fan R, et al. Genetic predisposition, modifiable lifestyles, and their joint effects on human lifespan: evidence from multiple cohort studies. BMJ Evidence-Based Medicine Published Online First: 29 April 2024.