Abstract
The beneficial effects of calorie restriction (CR) are numerous. However, there is no scientific evidence about how a high-calorie diet (HCD) background influences the mechanisms underlying CR on skeletal muscles in an experimental mouse model. Herein we present empirical evidence showing significant interactions between HCD (4 months) and CR (3 months). Pectoralis major and quadriceps femoris vastus medialis, in the experimental and control groups, displayed metabolic and physiologic heterogeneity and remarkable plasticity, according to the dietary interventions. HCD-CR not only altered genetic activation patterns of satellite SC markers but also boosted the expression of myogenic regulatory factors and key activators of mitochondrial biogenesis, which in turn were also associated with metabolic fiber transition. Our data prompt us to theorize that the effects of CR may vary according to the physiologic, metabolic, and genetic peculiarities of the skeletal muscle described here and that INTM/IM lipid infiltration and tissue-specific fuel-energy status (demand/supply) both hold dependent-interacting roles with other key anti-aging mechanisms triggered by CR. Systematic integration of an HCD with CR appears to bring potential benefits for skeletal muscle function and energy metabolism. However, at this stage of our research, an optimal balance between the two dietary conditions, where anti-aging effects can be accomplished, is under intensive investigation in combination with other tissues and organs at different levels of organization within the organ system.