Aging related obesity and type 2 diabetes mellitus suppress neuromuscular communication and aggravate skeletal muscle dysfunction in rhesus monkeys

Abstract

Age-related functional deterioration in skeletal muscle raises the risk for falls, disability, and mortality in the elderly, particularly in obese people or those with type 2 diabetes mellitus (T2D). However, the response of the skeletal muscle to transitioning from obesity to diabetes remains poorly defined, despite that obesity is classified as a stage of pre-diabetes. We screened and selected spontaneously obese and diabetic rhesus monkeys and examined altered protein expression in skeletal muscle of healthy aging (CON), obesity aging (OB), and type 2 diabetes mellitus aging (T2D) rhesus monkeys using Tandem Mass Tags (TMT)-based quantitative proteomic analysis. In total, we identified 142 differentially expressed proteins. Muscle-nerve communication proteins were firstly suppressed at obese-stage. With the disintegration of skeletal muscle, mitochondrial complex I and other energy homeostasis relate proteins were significantly disordered at T2D stage. Indicating that aging related obesity suppressed muscle-nerve communication and contribute to T2D related functional deterioration of skeletal muscles in elderly rhesus monkeys. Some alterations of muscular functional regulator are detected in both obesity and T2D samples, suggesting some T2D related skeletal muscular hypofunctions are occurring at obesity or pre-obesity stage. Muscle-nerve communication proteins and muscular function related proteins could be potential therapy target or early diagnose marker of for skeletal muscular hypofunctions in aging obesity populations.