Chronic inflammation mediates the relationship between physical activity and telomere length.

A physically active lifestyle benefits cellular aging, however the mechanisms linking physical activity (PA) with longevity remain unclear. PA is associated with longer telomere length (TL), while shorter TL has been associated with increased cellular aging. Some research suggests increased levels of inflammatory markers, such as C-reactive protein (CRP), are associated with telomere dysfunction. We tested the hypothesis that CRP levels mediate the association between PA and TL. Using data from the UK Biobank, we analyzed adjusted leukocyte T/S ratio (relative telomere to single gene copy), serum CRP, and moderate-to-vigorous physical activity (MVPA) data via device-measured actigraphy. We applied general linear regressions and a causal mediation analysis with 10,000 bootstraps while controlling for a range of covariates (age, BMI, smoking status, sex, ethnicity, time between data collection, time wearing the accelerometer, and the Townsend Deprivation Index). Variables of interest were transformed to approximate normality. A total of 79,873 participants were included in the final analytic sample. MVPA and CRP were both significant predictors of TL (β = 3.03e - 03 [95%CI = 1.58e - 03, 4.47e - 03], p = 4.10e - 05; β =  - 1.36e - 03 [95%CI =  - 1.87e - 03, - 8.40e - 04], p = 2.52e - 07, respectively). The association between MVPA and TL was mediated by CRP, accounting for 8.65% [95% CI: 4.77%, 16.0%] of the total effect (β [95%CI] = 3.31e - 03 [1.84e - 03, 4.75e - 03], p < 2e - 16). Our analysis supports the hypothesis that CRP mediates the relationship between MVPA and TL. These novel findings suggest a potential pathway where PA is associated with lower CRP concentrations, which in turn is associated with longer average TL.