Identifying modifiable factors that accelerate or delay aging from genetic variations
Description
Background With global aging, slowing aging is an urgent priority. While inevitable, aging rate may be modifiable by various environmental factors. This study aims to identify modifiable factors that have causal associations with aging. This can inform strategies to extend healthspan and mitigate the societal burden of aging. Methods and Design We evaluated 51 potentially modifiable risk factors for their associations with aging by using a two-sample bidirectional Mendelian randomization (MR) framework from Genome-wide association studies of 12,230 to 766,345 individuals who were predominantly of European descent. MR analyses were primarily conducted using the inverse-variance-weighted method, followed by various sensitivity analyses. Results Among 51 potentially risk factors, we identified systolic blood pressure, transferrin saturation, body mass index, osteoarthritis and C reactive protein as key factors that significantly contribute to accelerated aging. Primarily, transferrin saturation exhibits a noteworthy impact on Hannum Age acceleration (β [SE] per 1-SD increase: 0.293 [0.081] year), Horvath Age acceleration (0.327 [0.104] year), GrimAge acceleration (0.273 [0.083] year) and PhenoAge acceleration (0.417 [0.106] year). Meanwhile, educational attainment was identified as an effective factor in slowing the aging process. This study provides unique quantitative insights into modifiable causal risk factors for aging. Conclusion The study provides unique quantitative insights into modifiable causal risk factors for aging. Our findings underscore valuable intervention targets capable of slowing biological aging and fostering healthy longevity - an indispensable reference for public health strategies and relevant clinical scenarios.
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We evaluated 51 potentially modifiable risk factors for their associations with aging by using a two-sample bidirectional Mendelian randomization (MR) framework from Genome-wide association studies of 12,230 to 766,345 individuals who were predominantly of European descent. MR analyses were primarily conducted using the inverse-variance-weighted method, followed by various sensitivity analyses. All other data are contained in the article and its supplementary information or available upon reasonable request.