Causal Associations of Self-Reported Walking Pace with Telomere Length in 405,981 middle-aged adults: a UK Biobank study

Objectives: Walking pace is a strong marker of functional and health status. We investigated whether walking pace is also associated with leucocyte telomere length (LTL), which is causally associated with several diseases and has been proposed as a marker of biological age. Methods: We used baseline data from UK Biobank participants recruited from March-2006 to July-2010. Walking pace was self-reported as slow, steady/average, or brisk. Accelerometer-assessed measures of total physical activity and intensity were included to support interpretation of walking pace data. LTL was measured by qPCR assay. Bi-directional Mendelian randomization (MR) analyses were undertaken to inform likely causal directions. Results: The analysed cohort comprised 405,981 adults (54% women) with mean age of 56.5 years (SD, 8.1) and body mass index 27.2 kg/m2 (SD, 4.7). Steady/average and brisk walkers had significantly longer LTL compared with slow walkers, with a Z-standardised LTL difference of 0.066 (0.053-0.078) and 0.101 (0.088-0.113), respectively. Associations remained but were attenuated following full covariate adjustment: 0.038 (0.025-0.051) and 0.058 (0.045-0.072), respectively. Accelerometer data (n=86,002) demonstrated a non-linear association between LTL and habitual movement intensity, but not total activity. MR analysis supported a causal association of walking pace on LTL, with an increase in Z-standardised LTL of 0.192 (0.077, 0.306) for each difference in walking pace category. No evidence of a causal association was observed for LTL on walking pace. Conclusion: Faster walking pace may be causally associated with longer LTL, which could explain some of the beneficial effects of brisk walking on health status.