Maintaining skeletal muscle mass: lessons learned from hibernation

Area of Science:

• Molecular biology
• Physiology
• Biochemistry

Background:

• Muscle disuse and starvation typically cause significant skeletal muscle catabolism and mass loss.
• Hibernating animals paradoxically maintain muscle mass despite prolonged inactivity and fasting.

Purpose of the Study:

• To investigate molecular pathways preserving skeletal muscle mass during hibernation in the 13-lined ground squirrel.
• To identify potential therapeutic targets for combating muscle atrophy.

Main Methods:

• Analysis of molecular pathways, including Akt and serum- and glucocorticoid-regulated kinase 1 (SGK1), in hibernating ground squirrels.
• Utilizing SGK1-null mice to assess the kinase's role in muscle atrophy induced by immobilization and starvation.
• Employing SGK1 overexpression in mice to evaluate its protective effects against muscle atrophy.

Main Results:

• Activated Akt levels were decreased in hibernating squirrels' skeletal muscle.
• Serum- and glucocorticoid-regulated kinase 1 (SGK1) was upregulated during hibernation, mitigating muscle mass loss.
• SGK1-null mice exhibited exacerbated muscle atrophy under immobilization and starvation, while SGK1 overexpression prevented it.

Conclusions:

• Serum- and glucocorticoid-regulated kinase 1 (SGK1) plays a crucial role in preventing skeletal muscle atrophy.
• SGK1 acts by downregulating proteolysis and autophagy while promoting protein synthesis.
• SGK1 represents a novel therapeutic target for treating various forms of muscle loss.