Aging skeletal muscle often weakens early, limiting repair after injury and contributing to stiffness, fat infiltration, and loss of fast-twitch fibers needed for quick, powerful movement. Researchers are now zeroing in on a molecular “go” signal that may be impaired during aging—hepatocyte growth factor (HGF).
In healthy muscle, HGF sits dormant within the supportive niche around muscle fibers. When tissue is damaged or mechanically stimulated, HGF is released and binds to c-Met receptors on satellite cells, the resident stem cells that restart proliferation and differentiation to rebuild muscle.
But aging appears to sabotage this repair pathway through a specific chemical modification: nitration. In prior work, scientists showed that nitro groups are added to two HGF sites (Y198 and Y250), disabling HGF’s ability to dock with c-Met—like a key that no longer fits its lock—thereby undermining regeneration.
Seeking a way to preserve HGF function rather than merely boost its levels, the team hypothesized that strong antioxidant chemistry might protect HGF from nitration or counteract the loss that nitration causes. They tested two sulfur-based trisulfide compounds known for redox activity: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS).
Laboratory results showed both compounds could suppress HGF nitration at Y198 and Y250. Yet c-Met binding was not fully restored, prompting the researchers to adjust the molar ratio of HGF to trisulfide from 1:4000 to 1:8000.
At the higher ratio, HGF’s c-Met binding affinity rose by more than two-fold, and nitration-related dysfunction—especially at Y198—became more resistant. The standout effect came from LASSS alone; GSSSG did not reproduce the same enhancement.
The researchers suggest LASSS may do more than scavenge reactive molecules: it may directly interact with HGF, inducing a subtle structural shift that yields an “enhanced” super-functional form capable of stronger receptor engagement and greater nitration tolerance.
To probe whether this translates in living tissue, the team used a mouse model of muscle atrophy induced by tail suspension. Mice pretreated with LASSS showed markedly reduced HGF nitration compared with untreated controls, confirming LASSS’s protective activity beyond cell experiments.
Further aging studies are needed to confirm effectiveness and safety in vivo, but the findings point toward a viral-science-ready concept: a single targeted chemistry change that keeps muscle repair signals working longer.
Subject of Research:
Not applicable
Article Title:
Enhanced HGF with increased receptor affinity and nitration-dysfunction resistance through interaction with lipoic acid trisulfide
News Publication Date:
24-Jul-2026
Web References:
http://dx.doi.org/10.1038/s41598-026-60835-w
References:
10.1038/s41598-026-60835-w
Image Credits:
Kyushu University
Keywords:
aging muscle, HGF, c-Met, satellite cells, nitration, trisulfide, lipoic acid trisulfide, LASSS, muscle atrophy, regenerative medicine
