Sarcopenia as a causal mediator in aging, obesity and central obesity related outcomes: A comprehensive analysis of NHANES, CHARLS and ELSA.

BACKGROUND AND AIM: Sarcopenia, characterized by decreased muscle mass or muscle dysfunction, is associated with cardiovascular disease and mortality. However, the mediating effect of sarcopenia on the relationship between aging or obesity (especially central obesity) and adverse outcomes remains unclear.

METHODS AND

RESULTS

Sarcopenia was defined using functional criteria in the China Health and Retirement Longitudinal Study (CHARLS) and the English Longitudinal Study of Ageing (ELSA). In the National Health and Nutrition Examination Survey (NHANES) sarcopenia was determined using the skeletal muscle index (SMI) derived from appendicular skeletal muscle mass. A causal mediation analysis using counterfactual framework was conducted to estimate the mediating effect of sarcopenia on mortality associated with aging, obesity or central obesity. Sarcopenia was consistently associated with increased all-cause mortality, particularly among older adults. The combination of aging and sarcopenia amplified both mortality and cardiovascular disease (CVD) risks across cohorts. Sarcopenia partially meditated age-related all-cause mortality and cardiovascular outcomes by 8.67 % and 8.5 % in CHARLS (n = 9433), 8.56 % and 7.48 % in ELSA (n = 4389), 4.36 % and 3.95 % in NHANES (n = 16511), respectively. In NHANES but not other two cohorts, sarcopenia attenuated the adverse effects of obesity on mortality, and mediated the impact of central obesity on all-cause mortality. Subgroup and sensitivity analyses confirmed the robustness of these findings, showing similar mediation patterns across BMI categories or continuous exposure variables.

CONCLUSIONS

Sarcopenia partially mediates age-related mortality and cardiovascular risk, and modulates obesity-related outcomes variably across cohorts. Evidence-based sarcopenia prevention strategies may offer a promising strategy to reduce age- and obesity-associated health risks.