SIRT1 induction in the skeletal muscle of male mice partially preserves limb muscle mass but not contractile force in response to androgen deprivation

In males, the factors that decrease limb muscle mass and strength in response to androgen deprivation are largely unknown. Sirtuin1 (SIRT1) protein levels are lower in the limb muscle of male mice subjected to androgen deprivation. The present study aimed to assess whether SIRT1 induction preserved limb muscle mass and force production in response to androgen deprivation. Physically mature male mice containing an inducible muscle-specific SIRT1 transgene were subjected to a sham or castration surgery and compared to sham and castrated male mice where the SIRT1 transgene was not induced. SIRT1 induction partially preserved whole-body lean mass, tibialis anterior (TA) mass and triceps surae muscle mass in response to castration. Further analysis of the TA muscle showed that muscle-specific SIRT1 induction partially preserved limb muscle soluble protein content and fibre cross-sectional area. Unilateral AAV9-mediated SIRT1 induction in the TA muscle showed that SIRT1 partially preserved mass by acting directly in the muscle. Despite those positive outcomes to limb muscle morphology, muscle-specific SIRT1 induction did not preserve the force generating capacity of the TA or triceps surae muscles. Interestingly, SIRT1 induction in females did not alter limb muscle mass or limb muscle strength even though females have naturally low androgen levels. SIRT1 also did not alter the androgen-mediated increase in limb muscle mass or strength in females. In all, these data suggest that decreases in SIRT1 protein in the limb muscle of males may partially contribute to the loss of limb muscle mass in response to androgen deprivation. KEY POINTS: SIRT1 induction in skeletal muscle of male mice subjected to androgen deprivation partially preserved limb muscle mass and fibre cross-sectional area. SIRT1 induction in skeletal muscle of male mice subjected to androgen deprivation did not prevent preserve limb muscle force generating capacity. SIRT1 induction in skeletal muscle of females did not alter baseline limb muscle mass, nor did it affect the androgen-mediated increase in limb muscle mass.