Muscle-Adipose Aging Dynamics and Inflammaging Patterns Across Ethnically Diverse Populations: Exploring Potential Roles of Lipolysis.

<h4>Background</h4>Muscle-adipose aging reflects interactions between body composition changes and chronic inflammatory processes, but age-related patterns in these measures across ethnically diverse populations remain incompletely described. Understanding population-specific patterns is crucial for developing tailored prevention and intervention strategies. We aimed to characterize age- and sex-specific patterns of muscle-related measures, adiposity, inflammatory markers and lipolysis-related biomarkers within large cohorts from the United Kingdom, the United States and Taiwan, and to examine how these observed patterns varied across cohorts.<h4>Methods</h4>In this cross-cohort comparative study, we analysed data from UK Biobank (n = 35 436), US NHANES (n = 9157) and Taiwan NAHSIT (n = 4959). We examined age-related trajectories of muscle mass, adiposity, muscle-to-fat ratio, and biomarkers of inflammation and lipolysis. Inflammaging(definition) was assessed using C-reactive protein (CRP) and insulin-like growth factor-1 (IGF-1) decline profiles. Lipolytic activity was evaluated using circulating ketone bodies (β-hydroxybutyrate, acetoacetate, acetone) in the UK cohort. Age-specific patterns were described across populations, with particular attention to masking effects of body mass index (BMI) adjustment and late-life metabolic selection.<h4>Results</h4>Muscle-adipose aging patterns differed substantially across populations. Taiwanese men, despite having lower absolute appendicular lean mass, showed steeper cross-sectional differences while maintaining higher muscle-to-fat ratios than other cohorts. Inflammaging patterns were consistent across cohorts, with CRP increasing by up to 90% and IGF-1 declining by 20.3%-23.8% from ages 45 to 79, consistent with a potential link between chronic inflammation and anabolic resistance. BMI-adjusted muscle mass showed greater deterioration with age compared with height-adjusted measures, suggesting conventional assessments may mask sarcopenic progression. Adiposity trajectories peaked earlier in Western populations (55-59 years) than in Taiwanese adults (60-64 years), followed by late-life declines of 10.3%-23.5%, indicative of differential lipolytic activation. In the UK cohort, ketone body concentrations increased with age, suggesting higher fat oxidation in older age groups. Among adults aged 80 years or older, reversals in the muscle-to-fat ratio suggested metabolic selection effects across all populations.<h4>Conclusions</h4>Muscle-adipose aging reflects population-specific patterns of inflammatory and lipolytic reprogramming, with metabolic efficiency-rather than absolute tissue quantity-emerging as a key determinant of healthy aging. Establishing ethnically tailored reference standards may improve the precision of aging-related risk stratification and interventions across diverse populations.