Scientists in Japan have identified a compound that strengthens a key protein involved in muscle repair, potentially offering a new approach to age-related muscle decline.
The research team, led by Professor Ryuichi Tatsumi at Kyushu University's Faculty of Agriculture, published their findings in Scientific Reports. They focused on hepatocyte growth factor, or HGF, a protein that activates satellite cells. These specialized stem cells normally lie dormant alongside muscle fibers until they receive signals to repair damaged tissue.
With aging, HGF undergoes a chemical modification called nitration at two specific sites, Y198 and Y250. This change reduces HGF's ability to bind to c-met, a receptor on satellite cells that triggers muscle repair. The result resembles a key that no longer operates its lock.
The researchers tested two sulfur-based antioxidant compounds: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS). In laboratory experiments, LASSS produced an unexpected result. At higher concentrations, it increased HGF's binding affinity for c-met by more than twofold compared with untreated HGF. The compound also made HGF more resistant to nitration damage.
GSSSG reduced nitration but did not improve receptor binding, suggesting the effect was specific to LASSS.
"This exceeded our expectations," Tatsumi said. "We knew trisulfides had diverse biological functions, but we never expected that simply mixing HGF with LASSS would produce such a striking effect."
In mouse experiments using tail suspension to induce muscle atrophy, mice that received LASSS showed significantly less HGF nitration than untreated animals. The researchers suspect LASSS interacts directly with HGF and alters its three-dimensional shape, creating what they call "Super HGF."
The team noted that stronger receptor binding does not automatically prove improved muscle regeneration. Additional experiments will be needed to determine whether this molecular enhancement translates into better muscle healing.