GDF-8 (Myostatin)

GDF-8 (myostatin) is a TGF-β family protein that suppresses skeletal muscle growth. Inhibiting GDF-8 can increase muscle mass, improve bone density, and enhance metabolic health; research targets include muscular dystrophy, sarcopenia, and cachexia.

- Seek to reduce muscle wasting and promote hypertrophy

- Aim to enhance bone density and metabolic parameters

Mechanism of Action

How this peptide works in the body

Myostatin Receptor Binding and SMAD Pathway Activation:

GDF-8 (myostatin) binds to activin type II receptors (ActRIIB primarily, and ActRIIA), which then recruit and phosphorylate type I receptors (ALK4/ALK5). This receptor complex phosphorylates SMAD2/3, which dimerize with SMAD4 and translocate to the nucleus to suppress myogenic regulatory factors (MyoD, myogenin) and upregulate p21, inhibiting muscle cell proliferation and differentiation. Inhibition of Anabolic Pathways:

GDF-8 suppresses the PI3K/Akt/mTOR pathway by downregulating IGF-1 receptor signaling. This leads to decreased phosphorylation of Akt, reducing activation of mTORC1 and S6K1, which are essential for protein synthesis and hypertrophy. Simultaneously, atrogin-1 and MuRF1 expression is upregulated, accelerating protein degradation via the ubiquitin–proteasome system. Satellite Cell Suppression:

Myostatin inhibits the activation and differentiation of satellite cells—muscle stem cells responsible for regeneration. It downregulates Pax7, MyoD, and myogenin, blocking the regenerative response and contributing to muscle wasting in catabolic states. Bone and Marrow Interaction:

GDF-8 impairs osteoblastogenesis by antagonizing BMP signaling, thereby inhibiting Runx2-mediated bone formation. It also alters mesenchymal stem cell lineage, favoring adipogenic over osteogenic differentiation, which can lead to increased marrow fat and reduced bone mass. Metabolic Regulation and Insulin Sensitivity:

GDF-8 reduces GLUT4 translocation, limiting glucose uptake in muscle tissue, and suppresses AMPK activation. This contributes to insulin resistance. Myostatin also elevates TNF-α and IL-6, promoting systemic inflammation. Inhibition of myostatin improves insulin signaling, enhances mitochondrial biogenesis via PGC-1α, and decreases visceral fat mass.