U-shaped relationship of leucocyte telomere length with all-cause and cancer-related mortality in older men

BACKGROUND: Telomeres are essential DNA-protein complexes whose attrition results in cellular dysfunction and senescence. Leucocyte telomere length (LTL) correlates with tissue telomere length, representing a biomarker for biological age. However its predictive value for mortality risk, and for cardiovascular vs cancer deaths, in older adults remains uncertain.

METHODS: We studied 3,608 community-dwelling men aged 77.0±3.6 years. LTL was measured using multiplex quantitative PCR, expressed as amount of telomeric DNA relative to single-copy control gene (T/S ratio). Deaths from any cause, cardiovascular disease (CVD) and cancer were ascertained using data linkage. Curve fitting used restricted cubic splines and Cox regression analyses adjusted for age, cardiometabolic risk factors and prevalent disease.

RESULTS: There was a U-shaped association of LTL with all-cause mortality. Men with T/S ratio in the middle quartiles had lower mortality (quartiles, Q2 vs Q1, hazard ratio HR=0.86, 95% confidence interval CI=0.77-0.97, p=0.012, Q3 vs Q1 HR=0.88, CI=0.79-0.99, p=0.032). There was no association of LTL with CVD mortality. There was a U-shaped association of LTL with cancer mortality. Men with LTL in the middle quartiles had lower risk of cancer death (Q2 vs Q1, HR=0.73, CI=0.59-0.90, p=0.004, Q3 vs Q1, HR=0.75, CI=0.61-0.92, p=0.007).

CONCLUSIONS: In older men both shorter and longer LTL are associated with all-cause mortality. A similar U-shaped association was seen with cancer deaths, with no association found for cardiovascular deaths. Further research is warranted to explore the prognostic utility of LTL in ageing.