Advancing Age Enhances AKT Activity and Expression in Skeletal Muscle Without Suppressing Contractile Protein Degradation and Atrogin‐1 Expression

Abstract

The purpose of this study was to determine if sarcopenia is associated with insulin resistance, impaired AKT signaling, and increased contractile protein degradation rates. Insulin sensitivity was assessed by an insulin‐assisted glucose tolerance test (IAGTT) in middle‐aged (MA, 11–13 months) and aged (AG, 24–26 months) male C57B/6 mice. Contractile protein degradation rates were assessed by measuring 3‐methyl histidine release from isolated soleus (SOL) and extensor digitorum longus (EDL) muscles. During the IAGTT, blood glucose levels were significantly lower in AG mice compared to MA mice, indicating an improvement in insulin sensitivity with advancing age. The increase in insulin sensitivity observed in AG mice was associated with a significant increase in the phosphorylation of AKT in SOL and EDL muscles from AG compared to MA mice. The increase in AKT phosphorylation appears to be due to significant increases in both AKT1 and AKT2 expression. The phosphorylation of FOXO3a was significantly higher in EDL muscles from AG mice compared MA mice, but no age‐related differences in FOXO3a phosphorylation were observed in SOL muscles. The expression of the ubiquitin ligase, Atrogin‐1, was similar in SOL and EDL muscles from AG and MA mice. These results indicate that sarcopenia is not related to a decline in the ability of AKT to suppress Atrogin‐1 expression and contractile protein degradation.