Association of biological age acceleration with muscle aging phenotype in young and middle-aged adults: a prospective...

Loss of muscle mass and quality (myopenia and myosteatosis) are hallmarks of aging and predictors of disability, yet their relationship with biological aging in younger adults is unclear. This prospective cohort study included 165,015 adults (mean age 39.9) who underwent low-dose chest computed tomography (CT) between 2010 and 2020. A longitudinal subset of 61,669 participants had repeated scans (median follow-up 4.1 years). We adopted blood-based Phenotypic Age acceleration (PhenoAgeAccel) and chest radiograph-based biological age acceleration (CXR-AgeAccel). Myopenia and myosteatosis were defined as muscle area and density values more than two standard deviations below young sex-specific reference means. Multivariable multinomial logistic and Cox proportional hazard models estimated associations between biological age acceleration and prevalent or incident muscle abnormalities, adjusting for sociodemographic, lifestyle, and clinical factors. PhenoAgeAccel was associated with higher odds of myopenia (OR 1.16, 95% CI 1.08-1.25), myosteatosis (OR 1.24, 95% CI 1.18-1.29), and combined myopenia-myosteatosis (OR 1.51, 95% CI 1.41-1.63). In longitudinal analyses, PhenoAgeAccel was associated with increased risk of incident myopenia (HR 1.21, 95% CI 1.08-1.35), myosteatosis (HR 1.18, 95% CI 1.09-1.28), and the combined myopenia-myosteatosis (HR 1.29, 95% CI 1.08-1.55). Associations were consistent, though attenuated, with CXR-AgeAccel (OR 1.34, 95% CI 1.20-1.50; HR 1.18, 95% CI 0.96-1.45). Associations persisted among participants < 40 years. Accelerated biological aging measured from routine blood and imaging data was associated with early deterioration in muscle mass and quality. Biological age may represent a practical marker for identifying individuals at risk of early musculoskeletal decline.