Effects of aging, insulin resistance, and AKT gene ablation on muscle atrophy related gene expression

Aging and insulin resistance have been shown to result in muscle atrophy, a process that is associated with increased expression of atrophy related genes (ATRO‐GENES) and decreased AKT activity. The purpose of the present study was to determine if a high fat diet (HFD), aging, or AKT gene ablation increases the expression of ATRO‐GENES that control ubiquitin‐proteasome or autophagy/lysosomal protein degradation. Atg3 and Atg12 mRNA levels increase significantly in muscles from mice fed a HFD compared to a normal chow diet (NCD). Atrogin‐1, Gabarapl and Atg7 mRNA levels showed a strong trend to decrease while Bnip3 and LC3 did not change in muscles of mice fed a HFD compared to a NCD. When comparing the expression of ATRO‐GENES in muscles of aged mice (25 months old) with middle‐aged mice (11 months old), Bnip3 and Gabarapl mRNA levels decrease significantly; whereas, LC3, Atg12, atrogin‐1, and MURF1 mRNA levels did not change. In muscles of aged AKT1 and aged AKT2 knockout mice, Bnip3 mRNA increases significantly but atrogin‐1 mRNA does not change when compared to muscles of age‐matched wild type mice. These results indicate that advancing age, diet‐induced insulin resistance, and AKT gene ablation do not increase ubiquitin‐proteasome protein degradation. Our study suggests that advancing age decreases autophagy/lysosomal protein degradation, a process that may be regulated by AKT. Supported by 1R15AG031504‐01