The naturally occurring peptide GHK reverses age-related fibrosis by modulating myofibroblast function.

Fibrotic disorders, such as idiopathic pulmonary fibrosis, are characterized by the accumulation of myofibroblasts, cells responsible for excessive extracellular matrix deposition and tissue remodeling. The inability to terminate this reparative process leads to persistent fibrosis with increasing age. GHK (glycyl-L-histidyl-L-lysine], a naturally occurring peptide, has demonstrated the potential in modulating fibrotic pathways by reversing cellular senescence and inducing apoptosis in myofibroblasts. GHK promotes tissue regeneration and enhances wound healing by activating stemness markers like p63 and PCNA. In aging, GHK's effect on pulmonary fibroblasts may restore youthful phenotypes, improving fibroblast migration and collagen contraction. This commentary discusses the role of GHK in resolving persistent fibrosis and the molecular mechanisms underpinning these effects, including integrin-β1 signaling. The potential of GHK as a therapeutic agent for fibrosis, including combination strategies with antioxidants or anti-inflammatory agents, is also explored.