Impact of physical activity on mitochondrial enzymes, muscle stem cell and anti-oxidant protein Sestrins in Sarcopenic mice.

INTRODUCTION

Sarcopenia is the loss of skeletal muscle mass and function. It is a major health issue in old age due to lack of understanding of the origin and molecular mechanism. Altered dietary pattern, sedentary lifestyle and physical inactivity have shown adverse effect of skeletal muscle function. Sedentary behaviour and low protein intake have been well associated with sarcopenia. Here, we aim to develop Sarcopenia mimicking murine model to observe the physiological and biochemical changes with physical activity intervention. We also intended to find the association of muscle stem cells and stress induced protein Sestrins in the developed sarcopenic model.

METHODS

Male C57BL/6 mice were categorized into 4 groups: young-control (Y-Cntrl), aged-matched control (A-Cntrl), Sarcopenic-model (SAR-model) and Sarcopenic intervention group (SAR-INT) with physical exercises. SAR-model group was kept in a retrofitted confined cage for sedentary lifestyle and was fed with protein-restricted diet. Phenotypic assessment for body mass, grip strength and functional endurance was analysed to confirm the sarcopenic state. Mitochondrial enzymatic assessment, muscle stem cell (MuSCs) proliferation potential and protein quantification of Sestrins expression were performed by enzyme histochemistry, flow cytometry and surface plasmon resonance (SPR), respectively. SAR-model group was given 10 weeks physical activity intervention to assess the physiological and biochemical changes.

RESULTS

Simultaneous implementation of physical inactivity by sedentary confinement and protein restricted diet led the animals to exhibit the features of sarcopenia. SAR-model group showed a decline of 8.6% (p < 0.0001) in the body weight assessment, 32% decline (p < 0.0001) in the grip strength, 28% increase in time elapsed (p < 0.0001) indicating decline in functional performance. Mitochondrial enzymes (ATPase, NADH-TR and SDH/COX) assessment exhibited low expression in SAR-model group. Ki67 positive muscle stem cell declines around 50% in the model group. SPR quantification of Sestrin 2 showed a decline of 14% which significantly improved to 28% upon physical activity intervention (p = 0.0025) in SAR-INT group.

CONCLUSION

It can be summarized that the mouse model generated in the present study mimics the feature of human Sarcopenia. Physical activity intervention may improve the sarcopenic status via modulation of Sestrin 2 which can serve as potential molecule for therapeutic implication.