| Title: | Leisure-Time Physical Activity, Sedentary Behavior, and Biological Aging: Evidence From Genetic Correlation and Mendelian Randomization Analyses |
| Journal: | Scandinavian Journal of Medicine and Science in Sports |
| Published: | 10 Jan 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39794269/ |
| DOI: | https://doi.org/10.1111/sms.70014 |
Publication 14536
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
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 (rg = -0.18 to -0.29) and positively genetically correlated with LST (rg = 0.22-0.37). Univariable MR yielded a robust effect of genetically predicted LST on GrimAgeAccel (βIVW = 0.69, p = 1.10 × 10-7), while genetically predicted MVPA (βIVW = -1.02, p = 1.50 × 10-2) and LST (βIVW = 0.37, p = 1.90 × 10-2) showed marginal effects on PhenoAgeAccel. Multivariable MR suggested an independent association between genetically predicted LST and GrimAgeAccel after accounting for MVPA and other important confounders. Tissue-partitioned MR suggested skeletal muscle tissue associated variants to be predominantly responsible for driving the effect of LST on GrimAgeAccel. Findings support sedentary lifestyles as a modifiable risk factor in accelerating epigenetic aging, emphasizing the need for preventive strategies to reduce sedentary screen time for healthy aging.</p>
8 Keywords
- Aging
- Epigenesis, Genetic
- Exercise
- Genome-Wide Association Study
- Humans
- Leisure Activities
- Mendelian Randomization Analysis
- Sedentary Behavior
25 Authors
- Xunying Zhao
- Xueyao Wu
- Lin He
- Jinyu Xiao
- Rong Xiang
- Linna Sha
- Mingshuang Tang
- Yu Hao
- Yang Qu
- Changfeng Xiao
- Chenjiarui Qin
- Jiaojiao Hou
- Qin Deng
- Jiangbo Zhu
- Sirui Zheng
- Jinyu Zhou
- Ting Yu
- Bin Yang
- Xin Song
- Tao Han
- Jiaqiang Liao
- Tao Zhang
- Mengyu Fan
- Jiayuan Li
- Xia Jiang
Enabling scientific discoveries that improve human health