Exercise Training Ameliorates Cardiac Aging Of Mice Through Activating Apelin/apj System

Abstract

PURPOSE: Apelin/APJ system is known to improve cardiovascular disease. Exercise training has been associated with benefits against cardiac diseases and aging associated disorders. Our previous research showed that the serum Apelin levels decreased with age and exogenous Apelin intervention or overexpression of its receptor APJ could reverse the aging phenotype in D-galactose-induced aging cardiomyocytes. Herein we investigated the role Apelin/APJ system played in exercise training ameliorates cardiac aging. METHODS: The aging heart was simulated in 24 weeks-old senescence-accelerated mice. Mice were subjected to 6 weeks treadmill training, and treated with or without intraperitoneal injection of the apelin receptor antagonist - F13A 75ug/kg per day during training. The effects of treadmill training on circulating Apelin, myocardial Apelin / APJ, cardiac aging phenotype and mitochondrial autophagy were evaluated. RESULTS: Exercise training reduced weight loss, myocardial fibrosis and cardiac expression of aging biomarkers (p16, p53 and p21) in aged mice. In addition, exercise training increased the expression of Apelin and APJ in cardiomyocytes and maintained mitochondrial homeostasis, as evidenced by expression of mitochondrial related proteins (PGC-1α, CPT1A, PINK1, Parkin, Drp-1 and fis-1). The cardioprotective effects of exercise training were weakened by inhibition of the Apelin/APJ system. CONCLUSIONS: Taken together, our research showed that exercise training ameliorated phenotype of cardiac aging and disruption of mitochondrial homeostasis through activating the Apelin/APJ system. Hence, pharmacological activation of the Apelin/APJ system may prove to be a promising prevention against aging related heart disease especially in subjects with intolerance of exercise.