Skeletal muscle hypertrophy is primarily driven by an increase in muscle protein synthesis (MPS) exceeding muscle protein breakdown, largely regulated by the mTOR signaling pathway.

When skeletal muscles are subjected to sufficient mechanical tension, such as during resistance exercise, a cascade of intracellular signaling events is initiated. A key player in this cascade is the mechanistic Target of Rapamycin (mTOR) pathway. Activation of mTOR, often stimulated by resistance training, adequate amino acid availability (especially leucine), and growth factors like insulin-like growth factor 1 (IGF-1), acts as a central regulator of muscle growth. mTOR integrates these signals and then phosphorylates downstream targets, such as S6K1 and 4E-BP1, which are crucial for initiating and regulating mRNA translation into new proteins. This sustained increase in muscle protein synthesis, particularly of contractile proteins like actin and myosin, leads to an accumulation of protein within the muscle fibers, causing them to enlarge and strengthen. This delicate balance between synthesis and breakdown dictates the net change in muscle mass.