Our research program is supported mainly by four grants entitled: 1. "In Vivo Regulation of Protein Turnover by hormones" - this addresses the question: Does insulin resistance or insulin deficiency cause muscle mitochondrial dysfunction in diabetes? or Does mitochondrial dysfunction causes insulin resistance?. We approach these questions by performing human studies involving multiple interventions and measurements of DNA damage, gene expression, fractional synthesis rates of specific proteins (translational rate) and functional measurements including muscle mitochondrial ATP production and endurance capacity. 2. "Mechanism of muscle wasting in aging": this addresses the question whether muscle weakness, wasting and reduced endurance resulting in metabolic syndrome occur as people become older because of reduced capacity to synthesize and degrade proteins and mitochondrial dysfunction. Multiple approaches including gene array and proteomic technologies are used to answer these questions. Measurements of expression of specific muscle proteins in human aging and their functional importance assessment in animal model are important parts of this program. 3. "Plasma Proteins as markers of insulin deficiency and diabetic complications": This addresses the question whether we can identify specific plasma proteins or their altered synthesis rate as a marker/markers of diabetic related complications. 4. Branched Amino Acids and muscle functions" This investigates the specific role of branched chain amino acids as regulators of muscle protein expression and mitochondrial function in young and elderly people. ALL these research are based in Mayo General Clinical Research Center.