Gaugler M, Brown A, Merrell E, DiSanto-Rose M, Rathmacher JA, Reynolds TH 4th. PKB signaling and atrogene expression in skeletal muscle of aged mice. J Appl Physiol 111: 192-199, 2011. First published May 5, 2011 doi:10.1152/japplphysiol.00175.2011The purpose of this study was to determine if PKB signaling is decreased and contractile protein degradation is increased in extensor digitorum longus (EDL) and soleus (SOL) muscles from middle-aged (MA) and aged (AG) mice. We also examined the effect of age on atrogene expression in quadriceps muscle. PKB activity, as assessed by Thr 308 and Ser 473 phosphorylation, was significantly higher in EDL and SOL muscles from AG than MA mice. The age-related increase in PKB activity appears to be due to an increase in expression of the kinase, as PKB-␣ and PKB- levels were significantly higher in EDL and SOL muscles from AG than MA mice. The phosphorylation of forkhead box 3a (FOXO3a) on Thr 32 , a PKB target, was significantly higher in EDL muscles from AG than MA mice. The rate of contractile protein degradation was similar in EDL and SOL muscles from AG and MA mice. Atrogin-1 and muscle-specific RING finger protein 1 (MuRF-1) mRNA levels did not change in muscles from AG compared with MA mice, indicating that ubiquitin-proteasome proteolysis does not contribute to sarcopenia. A significant decrease in Bcl-2 and 19-kDa interacting protein 3 (Bnip3) and GABA receptor-associated protein 1 (Gabarap1) mRNA was observed in muscles from AG compared with MA mice, which may contribute to age-related contractile dysfunction. In conclusion, the mechanisms responsible for sarcopenia are distinct from experimental models of atrophy and do not involve atrogin-1 and MuRF-1 or enhanced proteolysis. Finally, a decline in autophagy-related gene expression may provide a novel mechanism for impaired contractile function and muscle metabolism with advancing age. signal transduction; atrophy; sarcopenia; proteolysis SARCOPENIA, THE AGE-RELATED loss of muscle mass, is present in ϳ45% of people Ն65 yr of age (14). Sarcopenia is a core component of a frailty syndrome that increases the risk of falling, reduces functional independence, and increases susceptibility to acute and chronic disease (9). In the United States, the direct healthcare costs associated with sarcopenia have been estimated to exceed $18 billion per year, an amount that is likely to increase dramatically because of the expansion of the aging population (14). The precise cause of sarcopenia is not established, but the condition is associated with physical inactivity, insulin resistance, nutritional deficiencies, elevated proinflammatory cytokines, and decreases in growth-promoting hormones.Ultimately, muscle size is determined by the relative rates of protein synthesis and degradation. Since the average protein turnover rate is ϳ4 -6 g protein·kg body wt Ϫ1 ·day Ϫ1 , or 280 g protein/day for a 70-kg adult (19), small persistent changes in the rates of protein synthesis or protein degradation could lead to substantial changes in ...
Reynolds 4th TH, Merrell E, Cinquino N, Gaugler M, Ng L. Disassociation of insulin action and Akt/FOXO signaling in skeletal muscle of older Akt-deficient mice.
The purpose of this study was to determine whether diet‐induced insulin resistance and type 2 diabetes are associated with an increase in the expression of the muscle atrophy related genes atrogin‐1 and Bnip3. Mice were fed a high fat diet (HFD) or a normal chow (CON) diet for 8 months. Following the dietary intervention muscles were removed and processed for immuno‐blotting or quantitative polymerase chain reaction (qPCR) experiments to assess atrogin‐1 and Bnip3 protein and mRNA levels, respectively. We observed no effect of the high fat diet on atrogin‐1 and Bnip3 protein levels or mRNA levels. These results indicate that long‐term high fat diet interventions do not activate ubiquitin‐dependent protein degradation and/or autophagy. Identical experiments were conducted with muscles from genetically obese (Ob/Ob) mice. There was a significant decline in atrogin‐1 protein levels in muscles from Ob/Ob mice compared to CON mice. Furthermore, a trend existed for higher levels of Bnip3 expression in muscles from Ob/Ob mice (P = 0.078). These results suggest that the loss of muscle mass with severe type 2 diabetes is due, in part, to increased autophagy rather than ubiquitin mediated proteolysis. Alternative, a decline in atrogin‐1 levels in muscles from type 2 diabetics may lead to an accumulation of damage proteins resulting in skeletal muscle contractile dysfunction.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.