Genetic and phenotypic associations of social isolation and loneliness with sarcopenia.

Social isolation and loneliness are recognized risk factors for adverse aging outcomes, but their effects on sarcopenia remain understudied. This study investigated the independent and combined effects of social isolation and loneliness on the risk of incident sarcopenia in two large prospective cohorts: CHARLS (n = 8,856) and ELSA (n = 5,561), including participants aged 50 years and older free of sarcopenia at baseline. Sarcopenia was defined using AWGS2019 and the Revised European Consensus criteria. During mean follow-ups of 3.7 years (CHARLS) and 3.9 years (ELSA), 1,431 and 331 incident sarcopenia cases were identified, respectively. Social isolation and loneliness were significantly associated with increased risk of sarcopenia in each cohort, and participants exposed to both had the highest risk. Population attributable fractions ranged from 5.6% to 14.4%. Mediation analysis revealed that the physical activity accounted for 6-9% of these associations. Mendelian randomization analyses further supported potential causal links, showing that predicted loneliness and isolation were associated with reduced grip strength and lower appendicular lean mass. These findings suggest that social isolation and loneliness are modifiable psychosocial risk factors for sarcopenia, partly mediated by physical inactivity. Public health efforts to prevent sarcopenia in older adults should include strategies to strengthen social connections and emotional well-being.