Along with reflecting cellular replicative history, telomere shortening is also moderated by factors such as oxidative stress and inflammation 24. ![]() The DNA component progressively shortens with each cell cycle, decreasing in most cell types as humans age, ultimately contributing to replicative senescence 19, 24. Telomeres are DNA–protein complexes that protect the ends of chromosomes from degradation, end-to-end fusion, and abnormal recombination of DNA strands (genomic instability). However, whether walking pace is causally associated with potential indicators of biological age remains unknown.Īlthough the relationship between leucocyte telomere length (LTL) and disease is complex 18, LTL has been proposed as a marker of biological age and is associated with higher risk of several age-related diseases including coronary artery disease and several cancers 18, 19, 20, 21, 22, 23. Therefore, it is possible that walking pace acts as both a marker and modulator of biological age. These factors also align with the concept of biological age, which relates to an individual’s ability to maintain a robust homoeostasis when subject to stressors 17. The importance of walking pace as a marker and potential promoter of health is likely to reflect it being a complex functional activity influenced by many factors, such as motor control, musculoskeletal health, cardiorespiratory fitness and lung capacity, habitual activity levels, cognition, motivation, and mental health 3, 13, 15. A genome-wide association study (GWAS) on self-reported walking pace within UK Biobank identified 70 independent SNPs at genome-wide significance 15, close to an order of magnitude greater than the number reported for other self-reported or accelerometer-assessed measures of physical activity traits within the same cohort 16. Similarly, accelerometer-assessed measures of physical activity in UK Biobank suggest that as little as 10 minutes of brisk walking a day is associated with longer life expectancy 14. Indeed, walking pace has been shown to have a stronger association with survival and be a substantially better prognostic marker for all-cause or cardiovascular mortality than other measures of physical activity volume, diet, or physical function 12, 13. Strong associations with health status have been seen for habitual or self-rated walking pace, which has been associated with better physical fitness and reduced risk of cardiovascular disease and all-cause mortality 6, 7, 8, 9, 10, with brisk walkers having up to 20 years greater life expectancy compared to slow walkers 11. It therefore holds potential as a pragmatic target for intervention 5. Walking is a simple and largely accessible form of physical activity for all ages, conferring many physical, mental, and social health benefits with minimal adverse effects 1, 2, 3, 4. Given its simple measurement and low heritability, self-reported walking pace may be a pragmatic target for interventions. ![]() A faster walking pace may be causally associated with longer LTL, which could help explain some of the beneficial effects of brisk walking on health status. Bi-directional mendelian randomisation analyses suggest a causal link between walking pace and LTL, but not the other way around. We show that steady/average and brisk walkers had significantly longer LTL compared with slow walkers, with accelerometer-assessed measures of physical activity further supporting this through an association between LTL and habitual activity intensity, but not with total amount of activity. Analyses were conducted in 405,981 UK Biobank participants. Here we investigate whether walking pace is associated with LTL, which is causally associated with several chronic diseases and has been proposed as a marker of biological age. Walking pace is a simple and functional form of movement and a strong predictor of health status, but the nature of its association with leucocyte telomere length (LTL) is unclear.
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