Prolonged exposure to leisure screen time notably accelerates biological aging: Evidence from observational studies and genetic associations.

LST is steadily increasing and is associated with various health issues. However, its impact on aging remains unclear. A total of 7212 participants from NHANES 1999-2002 were included. LTL, ALM, and FI were selected as aging phenotypes. Observational association between LST and aging traits was analyzed using linear regression models. MR analyses based on 112 genetic variants were performed to test the causal estimates from LST on aging. TWAS and PPI analyses were conducted to investigate underlying biological mechanisms. After adjusting for physical activity, per 1 ​h increase in LST, participants had a shorter LTL (β ​= ​-1.39, 95 ​% CI: -2.47 to -0.30), a lower ALM (β ​= ​-1.09, 95 ​% CI: -1.39 to -0.70), and an increased FI (β ​= ​8.22, 95 ​% CI: 4.29 to 12.30). Likewise, TSMR analyses indicated that genetically increased LST was significantly associated with shorter LTL (β ​= ​-2.63, 95 ​% CI: -4.86 to -0.35), lower ALM (β ​= ​-6.56, 95 ​% CI: -9.43 to -3.60), and increased FI (β ​= ​20.16, 95 ​% CI: 15.73 to 24.77). The trend remained robust after tests for pleiotropy and heterogeneity, consistent with the results of MVMR. 4 hub genes and 15 co-localized genes are identified, respectively, from PPI networks and TWAS. Pathways related to immune reactions, oxidative stress, and protein metabolism were significantly enriched. This study revealed that increased LST is significantly associated with adverse aging phenotypes. Reducing LST may help alleviate the burden of aging.