Abstract
The extant corpus of observational studies has yielded an inadequate body of evidence to establish a causal relationship between physical activity (PA) and the process of aging. This study aimed to determine the causal effects of different intensities of PA on biological aging using a 2-sample Mendelian randomization (MR) approach. Pooled data on PA and aging proxies were extracted from genome-wide association studies on individuals of European ancestry in order to perform MR analysis. Five MR analysis techniques were employed to reduce potential biases and ensure the robustness of the data, with the inverse-variance weighted method serving as the primary output. Sensitivity experiments were conducted to assess heterogeneity and pleiotropy in order to guarantee the results' robustness. The results of the MR analysis demonstrated that genetically predicted walking activity was associated with longer telomere length (β = 0.118; 95% CI [0.022-0.215]; P = .01). Additionally, a significant negative causal relationship was identified between strenuous exercise and GrimAge (β = -1.432; 95% CI [-2.774 to -0.091]; P = .036). The robustness of these findings was further validated through conducting a series of sensitivity analyses. This research offers evidence supports a potential causal relationship between PA and slower aging. This connection is reflected in the preservation of telomere length and the slowing of GrimAge progression. As a result, encouraging PA could serve as an effective approach to mitigate the aging process.