Advancing age is associated with an increased risk of type 2 diabetes, which is exacerbated by the high prevalence of obesity in the aged. These disorders are risk factors for age-related diseases associated with significant morbidity and mortality, including cancer, cardiovascular disease, and Alzheimer?s disease. New approaches to maintain glucose homeostasis in the aged are therefore urgently needed. The objective of the proposed study is to test a reduced branched-chain amino acid diet, recently shown in mice to reverse diet induced obesity and insulin resistance, in a small nonhuman primate, the common marmoset. We will also gain insight into the molecular mechanisms induced by reduced dietary branched-chain amino acids through comparative metabolomic and proteomic analysis of blood and skeletal muscle samples from marmosets and from young and aged mice. These studies are urgently needed to understand if manipulation of specific dietary amino acids is a translatable intervention to promote metabolic health and increase healthspan.
This project seeks to determine if a diet low in branched chain amino acids can reverse diet-induced obesity in a primate model and to understand the molecular mechanisms behind such actions. Aged-and-obese Americans have a risk of developing type 2 diabetes of nearly 50% making them vulnerable to both direct negative consequences on lifespan and healthspan, as well as increasing risk for numerous age-related diseases including cardiovascular disease, cancer, and Alzheimer?s disease. New interventions to treat and prevent obesity and diabetes are thus urgently needed.
