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

Sarcopenia was consistently associated with increased all-cause mortality, particularly among older adults, across all three cohorts.

• Three cohorts were analyzed: CHARLS (n=9433), ELSA (n=4389), and NHANES (n=16511)
• Sarcopenia was defined using functional criteria in CHARLS and ELSA, and using skeletal muscle index (SMI) derived from appendicular skeletal muscle mass in NHANES
• The combination of aging and sarcopenia amplified both mortality and cardiovascular disease (CVD) risks across cohorts

Sarcopenia partially mediated age-related all-cause mortality across all three cohorts.

• Mediation proportion for age-related all-cause mortality was 8.67% in CHARLS (n=9433)
• Mediation proportion for age-related all-cause mortality was 8.56% in ELSA (n=4389)
• Mediation proportion for age-related all-cause mortality was 4.36% in NHANES (n=16511)
• A causal mediation analysis using counterfactual framework was used to estimate these mediating effects

Sarcopenia partially mediated age-related cardiovascular outcomes across all three cohorts.

• Mediation proportion for age-related cardiovascular outcomes was 8.5% in CHARLS
• Mediation proportion for age-related cardiovascular outcomes was 7.48% in ELSA
• Mediation proportion for age-related cardiovascular outcomes was 3.95% in NHANES
• Cardiovascular outcomes were assessed alongside all-cause mortality in each cohort

Sarcopenia attenuated the adverse effects of obesity on mortality in NHANES but not in CHARLS or ELSA.

• This finding was specific to the NHANES cohort (n=16511)
• The effect was not replicated in CHARLS or ELSA, indicating cohort-specific variation
• Subgroup and sensitivity analyses confirmed the robustness of these findings, showing similar mediation patterns across BMI categories or continuous exposure variables

Sarcopenia mediated the impact of central obesity on all-cause mortality in NHANES but not in the other two cohorts.

• This central obesity mediation finding was observed only in the NHANES cohort
• The finding was not replicated in CHARLS or ELSA
• Subgroup and sensitivity analyses confirmed robustness across BMI categories and continuous exposure variables

Subgroup and sensitivity analyses confirmed the robustness of the mediation findings across cohorts.

• Analyses showed similar mediation patterns across BMI categories
• Similar patterns were also observed when using continuous exposure variables
• These analyses supported the main findings regarding sarcopenia's mediating role in age- and obesity-related outcomes