A surprising discovery could help aging muscles repair themselves
Scientists have discovered a compound that transforms a natural muscle-repair protein into a more powerful version dubbed "Super HGF," more than doubling its ability to bind to a key receptor while protecting it from age-related chemical damage. The breakthrough, supported by early mouse experiments, could eventually help combat muscle loss and preserve strength as people age.
Key points
- Scientists at Kyushu University found a sulfur compound, LASSS, that more than doubled HGF's binding to its receptor c-met.
- HGF loses function when nitrated at sites Y198 and Y250, which may contribute to age-related muscle wasting.
- In mice, LASSS reduced HGF nitration, but studies in aging animals are still needed.
Scientists at Kyushu University's Faculty of Agriculture in Japan have identified a compound that strengthened a key muscle repair signal in laboratory experiments, the university-led team reported in Scientific Reports. The work was led by Professor Ryuichi Tatsumi.
The compound, lipoic acid trisulfide (LASSS), more than doubled the ability of hepatocyte growth factor (HGF) to bind to c-met, a receptor on satellite cells that help repair muscle. The researchers describe the result as an enhanced "Super HGF" form.
How aging disrupts muscle repair
HGF normally activates dormant satellite cells so they can multiply and restore damaged muscle fibers. The researchers' earlier work showed that nitration, a chemical modification at sites Y198 and Y250, reduces HGF's ability to connect with c-met.
Tatsumi said HGF is not necessarily missing with age but can be chemically altered after it is made. The team tested two antioxidant trisulfides, GSSSG and LASSS, to see whether either could protect the protein.
We knew trisulfides had diverse biological functions, but we never expected that simply mixing HGF with LASSS would produce such a striking effect.
— Ryuichi Tatsumi
Mouse results and next steps
At a higher molar ratio, LASSS made HGF bind c-met more than twice as strongly as untreated HGF and made it more resistant to nitration at Y198. GSSSG did not produce the same binding improvement.
In mice subjected to tail suspension, a method for studying muscle atrophy, animals given LASSS showed significantly less HGF nitration than untreated mice. The experiments showed protection against nitration, not restored muscle mass or strength, and the researchers say studies in aging animals are still needed.
