Leukocyte telomere length (LTL)

Leukocyte telomere length (LTL) is the average length of repetitive TTAGGG sequences capping chromosome ends in white blood cells, measured in kilobases (kb), used as a proxy for cumulative replicative stress. Two assay platforms exist: quantitative PCR (qPCR), cost-effective for large cohorts, and flow-FISH, which achieves lower inter-assay variability (CV ~10% vs ~16% for qPCR). LTL declines roughly 20-40 bp per year in adults; critically short telomeres activate p53-mediated senescence. In 422,797 UK Biobank participants, Bountziouka et al. (2022) identified smoking and brisk walking pace as the strongest modifiable correlates, though all tested traits combined explained less than 0.2% of variance. Shorter LTL correlates with higher cardiovascular and all-cause mortality risk at population level, but individual predictive value is limited by wide distributional overlap across age groups. Mendelian randomisation yields a heterogeneous picture: genetically shorter LTL raises risk for cardiovascular disease and multiple sclerosis, while longer LTL paradoxically increases risk for soft-tissue sarcoma and atrial fibrillation. Direct-to-consumer tests lack standardised reference ranges and explain only a modest fraction of biological-age variance relative to epigenetic clocks.