BACKGROUND:
Extending life expectancy of the elderly is a core goal of global healthy aging initiatives. The deep-seated influence of modifiable risk factors and genetic risks on healthy aging has not yet been fully elucidated. We aimed to investigate the joint associations of both with life expectancy among the oldest old.

METHODS:
This prospective, community-based cohort study included participants aged over 80 from the China Hainan Centenarian Cohort Study. A weighted modifiable risk factor score (MRFS) was derived from 11 factors and categorized into tertiles. A polygenic risk score (PRS) for longevity was constructed and dichotomized. We used Cox regression to assess associations and a flexible parametric survival model to estimate life expectancy.

RESULTS:
Among 1,545 participants (median follow-up 4.04 years), 1,020 deaths occurred. Compared with the high MRFS, individuals in the low MRFS had a lower death risk (HR 0.593, 95%CI 0.505-0.696). The HR of death risk for individuals with a genetic risk to high PRS was 0.870 (95% CI 0.768-0.986) compared to those with a genetic predisposition to a short lifespan. Participants with a low MRFS and a high PRS had 0.544 times (95%CI 0.432-0.686) lower rates of death risk compared with those with a high MRFS and a low PRS. Life expectancy gains from a low MRFS were more pronounced in those with a high PRS (gaining 6.92 years at age 80) than in those with a low PRS (gaining 5.35 years). Interpretation: In the oldest-old, favorable modifiable risk factor and genetic predisposition were associated with substantially increase life expectancy. Crucially, modifiable risk factors would largely attenuate the benefits of genetic risk for a longer lifespan. These findings underscore that comprehensive management of modifiable risk factors is pivotal for extending lifespan, even in advanced age and irrespective of genetic inheritance.