Aging-related changes in body composition across the lifespan - insights from over 66.000 individuals of a Western European population

Body composition (adiposity and muscle depots) is strongly associated with cardiometabolic risk. However, using body composition measures for future disease risk prediction is difficult as they may reflect total body size or typical aging rather than poor health. We used data from the UK Biobank (UKB) and the German National Cohort (NAKO) to calculate age-, sex-, and height-specific z-scores for body composition measures (subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), skeletal muscle (SM), SM fat fraction (SMFF), and intramuscular adipose tissue (IMAT)) and describe changes across the lifespan. Multivariable Cox regression assessed the prognostic value of z-score categories (low: z<-1; middle: z=-1 to 1; high: z>1) for incident diabetes, major adverse cardiovascular events (MACE), and all-cause mortality beyond traditional cardiometabolic risk factors in the UKB. Among 66,608 individuals (mean age: 57.7{+/-}12.9 y; mean BMI: 26.2{+/-}4.5 kg/m2, 48.3% female), SAT, VAT, SMFF, and IMAT were positively, and SM negatively associated with age. In multivariable-adjusted Cox regression, z-score risk categories had hazard ratios of up to 2.69 for incident diabetes (high VAT category), 1.41 for incident MACE (high IMAT), and 1.49 for all-cause mortality (low SM) compared to middle categories. Body composition shows distinct age-related changes across the lifespan. Z-scores of age-, sex-, and height-adjusted body composition measures identify individuals at risk and predict cardiometabolic outcomes and mortality beyond traditional risk factors. Our open-source tool facilitates the clinical translation of age-specific body composition assessments and supports future research. One Sentence SummaryAge-, sex-, and height-adjusted body composition z-scores predict cardiometabolic outcomes and enable clinical translation of body composition data.