Leisure‐Time Physical Activity, Sedentary Behavior, and Biological Aging: Evidence From Genetic Correlation and Mendelian Randomization Analyses

作者：Xunying Zhao, Xueyao Wu, Lin He, Jinyu Xiao, Rong Xiang, Linna Sha, Mingshuang Tang, Hao Yu, Yang Qu, Changfeng Xiao, Chenjiarui Qin, Jiaojiao Hou, Qin Deng, Jiangbo Zhu, Sirui Zheng, Jinyu Zhou, Ting Yu, Bin Tang Yang, Xin Song, Tao Han, Jiaqiang Liao, Tao Zhang, Mengyu Fan, Jiayuan Li, Xia Jiang · 发表于：Scandinavian Journal of Medicine and Science in Sports · 年份：2025 · DOI：10.1111/sms.70014 · 被引用次数：4 · 研究领域：Obesity, Physical Activity, Diet、Genetic Associations and Epidemiology、Physical Activity and Health

ABSTRACT Physical inactivity and sedentary behavior are associated with higher risks of age‐related morbidity and mortality. However, whether they causally contribute to accelerating biological aging has not been fully elucidated. Utilizing the largest available genome‐wide association study (GWAS) summary data, we implemented a comprehensive analytical framework to investigate the associations between genetically predicted moderate‐to‐vigorous leisure‐time physical activity (MVPA), leisure screen time (LST), and four epigenetic age acceleration (EAA) measures: HannumAgeAccel, intrinsic HorvathAgeAccel, PhenoAgeAccel, and GrimAgeAccel. Shared genetic backgrounds across these traits were quantified through genetic correlation analysis. Overall and independent associations were assessed through univariable and multivariable Mendelian randomization (MR). A recently developed tissue‐partitioned MR approach was further adopted to explore potential tissue‐specific pathways that contribute to the observed associations. Among the four EAA measures investigated, consistent results were identified for PhenoAgeAccel and GrimAgeAccel. These two measures were negatively genetically correlated with MVPA ( r g = −0.18 to −0.29) and positively genetically correlated with LST ( r g = 0.22–0.37). Univariable MR yielded a robust effect of genetically predicted LST on GrimAgeAccel ( β IVW = 0.69, p = 1.10 × 10 −7 ), while genetically predicted MVPA ( β IVW = −1.02, p = 1.50 × 10 −2 ) and LST ( β...