Leisure-Time Physical Activity, Sedentary Behavior, and Biological Aging: Evidence From Genetic Correlation and...

Area of Science:

• Genetics and Epigenetics
• Aging Research
• Public Health

Background:

• Physical inactivity and sedentary behavior are linked to increased morbidity and mortality.
• The causal role of these behaviors in accelerating biological aging remains unclear.

Purpose of the Study:

• To investigate the causal associations between genetically predicted physical activity and sedentary behavior with epigenetic age acceleration.
• To explore potential tissue-specific mechanisms underlying these associations.

Main Methods:

• Utilized large-scale genome-wide association study (GWAS) summary data.
• Employed genetic correlation, univariable and multivariable Mendelian randomization (MR).
• Applied a novel tissue-partitioned MR approach to identify tissue-specific effects.

Main Results:

• Leisure screen time (LST) showed a robust positive association with GrimAgeAccel, a measure of epigenetic aging.
• Moderate-to-vigorous physical activity (MVPA) and LST had marginal associations with PhenoAgeAccel.
• Multivariable MR confirmed LST as an independent predictor of GrimAgeAccel.
• Skeletal muscle tissue variants were implicated in the LST-GrimAgeAccel association.

Conclusions:

• Sedentary behavior, specifically increased leisure screen time, is a modifiable risk factor for accelerated epigenetic aging.
• Findings highlight the importance of reducing sedentary screen time for promoting healthy aging.
• Interventions targeting sedentary behavior may be crucial for mitigating age-related health risks.