Physical Resilience May Offset Mortality Risks Associated With Genetic Predisposition to Shorter Survival: A...

Physical resilience (PR), the ability to recover from health adversities, is thought to buffer health challenges during aging. However, PR's association with mortality and its ability to offset the negative effects of genetic susceptibility to shorter lifespan remains unknown.

Data on 3 041 individuals (age: 60+) from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) were analyzed. Physical resilience was assessed at baseline (2001-2004) using residual gait speed for a given level of chronic diseases, medications, and sociodemographics, categorized as low (residual SD's ≤ -1), moderate (-1 < SD < 1), or high resilience (SD ≥ 1). A genetic risk score was derived from 4 single nucleotide polymorphisms linked to longevity (hTERT, APOE, TOMM40, IGF-1R). Cox proportional hazard models and Laplace regression examined 18-year mortality and median survival, respectively. Physical resilience was assessed as the moderator of the genetic risk score-mortality association in stratified analysis.

Compared to individuals with moderate PR, those with low resilience had higher mortality risk (HR: 1.28; 95% CI [1.09, 1.51]), with the opposite pattern in those with high PR (HR: 0.71; 95% CI [0.60, 0.84]). Above-median levels of genetic risk score were associated with increased mortality risk (HR: 1.34; 95% CI [1.18, 1.52]). Stratified by PR, mortality risk associated with higher genetic risk score was elevated among those with low and moderate resilience but not among older adults with high resilience.

Physical resilience appears to partly modify mortality risk associated with genetic predisposition to shorter survival. Fostering PR could benefit personalized therapeutic strategies to support healthy aging.