Modifiable traits, healthy behaviours, and leukocyte telomere length: a population-based study in UK Biobank.
Level 3 - non-randomized controlled study
Cross-sectional cohort analysis with Mendelian randomisation
PubMed 35685390 · doi:10.1016/S2666-7568(22)00072-1
What was done
Cross-sectional and Mendelian randomisation analysis of 422,797 UK Biobank participants (53.8% women, 94.6% White) evaluating associations between leukocyte telomere length (LTL) and 117 potentially modifiable traits, alongside two composite healthy behaviour indices (smoking, physical activity, diet, bodyweight, alcohol). Trait associations were expressed as equivalent years of age-related change in LTL. Mendelian randomisation tested causality for selected associations, and analyses examined whether LTL modified associations with 22 diseases or mediated the relationship between healthy behaviours and life expectancy or coronary artery disease.
What was found
71 traits significantly associated with LTL (p < 4.27 × 10⁻⁴), but most accounted for less than 1 year of age-related LTL change. In multivariable models of 17 stronger traits (≥2 years age-equivalent change), oily fish intake, educational attainment, and general health status retained significant associations (with walking pace and current smoking also significant in imputed models). Mendelian randomisation suggested educational attainment and smoking causally affect LTL. Participants with the most healthy behaviours had longer LTL equivalent to ~3.5 years of age-related change compared to the least healthy (p < 0.001). However, healthy behaviours explained <0.2% of total LTL variance, did not modify disease associations across 22 conditions, and did not substantially mediate the association of healthy behaviours with life expectancy or coronary artery disease.
Why it matters
Modifiable lifestyle behaviours have a minimal impact on leukocyte telomere length and do not meaningfully mediate the life expectancy or cardiovascular benefits of healthy living. Interventions designed specifically to lengthen telomeres via lifestyle modification are unlikely to provide substantial clinical utility.
Limits
The cohort is predominantly White (94.6%) and subject to healthy volunteer selection bias. LTL was measured cross-sectionally in circulating leukocytes rather than longitudinally or across target disease tissues.
Cited by
- supports Higher educational attainment is positively correlated with longer leukocyte telomere length.