Ang-(1-7) Protects Skeletal Muscle Function in Aged Mice

Abstract Background: The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang-(1-7)) axis has been shown to perform a protective task in the decline of the function of skeletal muscle correlated with the process of aging. In the present investigation, the protective effects of ACE2 in mitigating the age-associated decline of skeletal function and identified the potential underlying molecular mechanism mediating the process have been extensively evaluated.Methods: We measured the expression levels of Ang-(1-7) in C57BL/6J mice of different ages and correlated these levels with measures of skeletal muscle function. Also, we determine the expression of myocyte enhancer factor 2A (MEF2A) were detected in ACE2 knockout (ACE2KO) and correlated with muscle function. We then treated ACE2KO aged mice for 4 weeks with Ang-(1-7) and characterized the levels of MEF2A and skeletal muscle function before and after treatment. We assessed the impact of Ang-(1-7) on the growth and differentiation of C2C12 cells in vitro and assessed changes in the glucose transporter type 4 (Glut4) expression.Results: Aged mice showed reduced skeletal muscle function and levels of Ang-(1-7) expression in comparison to young and middle-aged mice. In ACE2KO mice, skeletal muscle function and MEF2A protein expression were significantly lower than in age-matched WT mice. After 1 month of the treatment of Ang-(1-7), the function of skeletal muscle related to the aged ACE2KO mice improved, however, the expression of MEF2A protein was similar to that in the untreated group. In C2C12 cells, Ang-(1-7) was shown to increased cell growth and differentiation characteristics along with the upregulated expression of Glut4.Conclusions: The axis of ACE2/ Ang-(1-7) has a protective task in skeletal muscle and the administration of exogenous Ang-(1-7) can delay the age-related decline in the functions of skeletal muscle.