Jiang Chenke, Gan Yihong, Chen Shengyu, Yao Jie, Zhang Yilin, Fan Yongsheng, Wang Xinchang, Xu Li
School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Aging Clin Exp Res. 2025 Jul 22;37(1):227. doi: 10.1007/s40520-025-03043-2.
Observational studies have shown that physical activity and sedentary behavior are associated with aging. However, whether these associations underlie causal effects remains unknown. Thus, this study aimed to assess the genetic correlation and causal relationships between genetically predicted physical activity, sedentary behavior, and aging.
Using linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR). Genetic variants associated with leisure screen time (LST, as an indicator of sedentary behavior), moderate-to-vigorous physical activity (MVPA), and four aging-related traits (90th survival percentile, facial aging, telomere length, and frailty index) were obtained from genome-wide association studies (GWAS). The primary MR analyses were performed using the inverse variance weighted (IVW) method, followed by various sensitivity and validation analyses.
Univariable MR analysis indicated significant associations of LST with telomere length (β = - 0.04, P = 4.95E-06), and facial aging (β = 0.11, P = 2.28E-09), frailty index (β = 0.17, P = 1.93E-35). MVPA had a significant causality with the frailty index (β = - 0.28, P = 6.46E-09). These associations weakened in Multivariable MR Analysis, but the frailty index remained significantly correlated after adjustment. LDSC further supported the genetic correlations identified in the MR analysis. Additionally, pathway analyses, including the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), highlighted potential mechanisms linking LST and aging outcomes.
This study reveals that LST and MVPA may play a causal role in the process of aging. Accordingly, public health efforts to promote increased physical activity and reduce sedentary time can effectively combat accelerated aging.
观察性研究表明，身体活动和久坐行为与衰老有关。然而，这些关联是否构成因果效应尚不清楚。因此，本研究旨在评估基因预测的身体活动、久坐行为和衰老之间的遗传相关性及因果关系。
采用连锁不平衡评分回归（LDSC）和孟德尔随机化（MR）方法。从全基因组关联研究（GWAS）中获取与休闲屏幕时间（LST，作为久坐行为的指标）、中度至剧烈身体活动（MVPA）以及四个与衰老相关的特征（第90百分位生存率、面部衰老、端粒长度和衰弱指数）相关的基因变异。主要的MR分析采用逆方差加权（IVW）方法，随后进行各种敏感性和验证分析。
单变量MR分析表明，LST与端粒长度（β = -0.04，P = 4.95E-06）、面部衰老（β = 0.11，P = 2.28E-09）、衰弱指数（β = 0.17，P = 1.93E-35）存在显著关联。MVPA与衰弱指数存在显著因果关系（β = -0.28，P = 6.46E-09）。这些关联在多变量MR分析中有所减弱，但调整后衰弱指数仍保持显著相关性。LDSC进一步支持了MR分析中确定的遗传相关性。此外，包括京都基因与基因组百科全书（KEGG）和基因本体论（GO）在内的通路分析突出了连接LST和衰老结果的潜在机制。
本研究表明，LST和MVPA可能在衰老过程中发挥因果作用。因此，促进身体活动增加和减少久坐时间的公共卫生措施可以有效对抗加速衰老。
