Joint association of leukocyte telomere length and muscle mass with mortality: a longitudinal nationwide population-based study

Telomere and skeletal muscle mass are independent risk factors for mortality, but their joint effects have not been fully elucidated. Accelerated aging and unhealthy skeletal muscle are growing public health concerns in an aging society. We sought to investigate the joint effects of leukocyte telomere length (LTL) and muscle mass with mortality in the National Health and Nutrition Examination Survey (NHANES) 1999–2002. Telomere length was determined by quantitative polymerase chain reaction (qPCR), and skeletal muscle mass was measured by dual-energy X-ray absorptiometry (DXA), and expressed as limb skeletal muscle mass index (ASMI). The Cox proportional hazards regression model was used to analyze the association between it and all-cause mortality. A total of 4668 individuals (mean age 48.43 years, female 48.9%) were included. During a median follow-up of 16.92 years, there were 1,138 deaths (cardiovascular disease,288). 2,833 (60.7%) had neither lower LTL nor lower ASMI, 1,226 (26.3%) had only lower LTL, 364 (7.8%) had only lower ASMI, and 245 (5.2%) had both lower LTL and lower ASMI. Compared to the LTL normal /ASMI normal group, the LTL lower /ASMI normal , LTL normal /ASMI lower , and LTL lower /ASMI lower groups demonstrated increased all-cause mortality with adjusted hazard ratios (HRs) of 1.31 (95% confidence interval [CI]: 1.08, 1.58), 1.79 (95% CI: 1.44, 2.23), and 1.64 (95% CI: 1.32, 2.04), respectively. Similarly, participants with LTL lower and/or ASMI lower had a higher risk of cardiovascular disease mortality (HRs, 1.56–1.99) than those with LTL normal /ASMI normal . Further stratified analyses showed that the coexistence of LTL lower and ASMI lower additively increased the risk of all-cause mortality in younger participants (< 60 years) (HR 2.38, 95% CI: 1.22–4.65) and in women (HR 1.94, 95% CI: 1.28–2.96). In contrast, among older participants and men with LTL normal / ASMI lower , the risk of all-cause mortality was higher than among those with LTL lower /ASMI lower . Low telomere length and low skeletal muscle mass were jointly associated with greater risk of all-cause mortality, especially among younger individuals and women.