The study noted here is one of many to show that the effects of lifestyle choice and environmental exposure far outweigh the effects of genetic variants when it comes to late life survival. Yes, there are a few very rare genetic variants and mutations that produce effect sizes of at least several years, but for the vast majority of individuals mortality risk in old age is overwhelmingly determined by lifestyle and environment. Did you stay relatively thin and relatively fit? Were you unlucky in your exposure to infectious pathogens, particularly persistent infections? Did you self sabotage by smoking? And so forth.
In this prospective cohort study of 1,545 participants aged 80 years and older from the China Hainan Centenarian Cohort Study, we investigated the independent and joint associations of modifiable risk factors and genetic predisposition with life expectancy. A weighted modifiable risk factor score (MRFS) based on 11 factors and a polygenic risk score (PRS) for longevity were constructed.
A favorable modifiable risk factor profile (low MRFS) was associated with a 40.7% lower death risk (hazard ratio, HR = 0.593) compared with high MRFS. Genetic predisposition to longer lifespan (high PRS) conferred a 13.0% lower risk (HR = 0.870). Participants with both low MRFS and high PRS had the lowest mortality (HR = 0.544), with a borderline significant multiplicative interaction. Life expectancy gains from a low MRFS were more pronounced in those with high PRS (6.92 years at age 80) than low PRS (5.35 years).
In conclusion, among the oldest-old Han Chinese, favorable modifiable risk profiles and genetic predisposition independently and jointly contribute to substantially longer life expectancy. Importantly, an unfavorable modifiable profile may largely negate genetic longevity benefits, emphasizing the critical role of managing these factors even in advanced age and irrespective of genetic inheritance.
