Physical resilience may offset mortality risks associated with genetic predisposition to shorter survival: A population-based cohort study

Abstract Background 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 remain unknown. Methods Data on 3,041 individuals (age: 60+) from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) were analyzed. PR 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 (GRS) was derived from four SNPs linked to longevity (hTERT, APOE, TOMM40, IGF-1R). Cox proportional hazard models and Laplace regression examined 18-year mortality and median survival, respectively. PR was assessed as the moderator of the GRS-mortality association in stratified analysis. Results 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 GRS were associated with increased mortality risk (HR: 1.34; 95% CI [1.18, 1.52]). Stratified by PR, mortality risk associated with higher GRS was elevated among those with low and moderate resilience but not among older adults with high resilience. Conclusion PR appears to partly modify mortality risk associated with genetic predisposition to shorter survival. Fostering PR could benefit personalized therapeutic strategies to support healthy aging.