Lifestyle Produces a Much Greater Contribution to Human Life Expectancy than a Genetic Risk Score
Since the advent of very large databases of combined human genetic and epidemiological information, the evidence has increasingly leaned to support only a modest effect of genetic variation on human life span variation. Setting aside small populations with rare mutations, lifestyle has a much greater effect on life expectancy than one's genes. Even cases of familial longevity might largely result from transmission of culture, and thus lifestyle choices, rather than transmission of genetic variants.
Today's open access paper reports on data in which both genetic risk and lifestyle risk can be assessed. It is worth noting that the genetic risk is here limited to a consideration of only a few genes, but equally only a small number of genetic variants have been shown to robustly correlate with human life span. The thing to take away from the results is the degree to which the effects of a healthy lifestyle on life expectancy are similar for the high genetic risk and low genetic risk cohorts. In other words, the high genetic risk as assessed here isn't doing all that much to life expectancy when compared to the consequences of lifestyle choices.
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.
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 9,633 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.
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 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 0.56). The highest mortality risk was observed in individuals in the high genetic risk and unhealthy lifestyle group (hazard ratio 1.80). 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 at the age of 65 years in the low genetic risk group, and 4.35 years in the high genetic risk group.
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.