Circulating metabolomic biomarkers of 5-year body weight and composition change in a biracial cohort of community-dwelling older adults

Unintentional weight loss in older populations is linked to greater mortality and morbidity risks. This study aims to understand the metabolic mechanisms of unintentional weight loss and their relationship with body composition changes in older adults. We investigated plasma metabolite associations with weight and body composition changes over 5 years in 1335 participants (mean age 73.4 years at Year 1, 51% women, and 33% Black) from the Health, Aging and Body Composition (Health ABC) study. Multinomial logistic regressions were used to examine associations of the 442 metabolites with weight loss > 5% over 5 years with/without an intention, weight gain > 5%, and fluctuating weight relative to weight stability. Metabolite associations with unintentional weight loss differed from other weight change patterns. Lower levels of essential amino acids, phospholipids, long-chain polyunsaturated triglycerides, cholesterol esters, and uridine were associated with higher odds of unintentional weight loss versus weight stability after adjusting for age, sex, race, and Year 1 BMI categories. Losses in fat mass and muscle mass each attenuated > 20% of the associations between many metabolites, such as phospholipids and essential amino acids, and unintentional weight loss. DXA whole-body fat mass loss (mean 3% annually) further attenuated 9 metabolite associations by > 50% after CT muscle loss (mean 2% annually) adjustment. Lipids and amino acids related to energy and protein balance were associated with unintentional weight loss in older adults. Fat and muscle mass losses partially attenuated these associations, suggesting connections of these metabolic pathways with muscle, and particularly adiposity dynamics.