New Compound May Boost Aging Muscle Repair by Enhancing Key Protein

Researchers have identified a novel compound that shows significant promise in protecting and enhancing the signaling pathways crucial for muscle repair, particularly in aging individuals. The breakthrough, led by Professor Ryuichi Tatsumi at Kyushu University's Faculty of Agriculture, centers on a molecule that could potentially combat age-related muscle degeneration. These findings were officially published on July 24, 2026, in the journal Scientific Reports.

The core of this research lies in understanding how the body initiates muscle repair. Skeletal muscle regeneration relies heavily on a protein known as hepatocyte growth factor (HGF). Normally, HGF is kept inactive within the extracellular matrix surrounding muscle fibers. Upon injury or mechanical stress, HGF is released and then binds to specific receptors called c-met on satellite cells—the stem cells responsible for muscle maintenance and repair. This interaction activates the satellite cells, prompting them to multiply, differentiate, and contribute to rebuilding damaged muscle tissue.

However, the aging process can compromise this intricate repair system. Previous studies by Tatsumi's team revealed that HGF can undergo a process called nitration, where a nitro group attaches to specific sites (Y198 and Y250) on the protein. These sites are critical for HGF's binding to the c-met receptor. Once nitrated, HGF loses its effectiveness, akin to a 'rusted key that no longer fits its lock.' This impaired function is believed to be a significant factor in the muscle wasting and reduced regenerative capacity observed in older adults.

"HGF is not necessarily missing as we age," Professor Tatsumi explained. "Rather, it can be chemically altered after it is made. That led us to wonder whether a compound with strong antioxidant capacity might protect HGF, either by preventing nitration or by compensating for the functional loss it causes." This inquiry led the researchers to investigate sulfur-based antioxidants.

Testing Sulfur-Based Compounds and a Surprising Discovery

The scientists focused their attention on two compounds with potent antioxidant properties: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS). Both belong to the trisulfide class, characterized by a sequence of three sulfur atoms, and have garnered significant interest in pharmaceutical research due to their unique sulfur chemistry and involvement in redox reactions.

Initial laboratory experiments demonstrated that both GSSSG and LASSS could reduce the nitration levels at the Y198 and Y250 sites on HGF. However, neither compound was able to fully restore the protein's capacity to bind to its c-met receptor. The research team then adjusted the experimental conditions, increasing the molar ratio of HGF to trisulfide from 1:4000 to 1:8000.

This adjustment yielded a remarkable and unexpected outcome. When HGF was incubated with LASSS at the higher concentration, its ability to bind to the c-met receptor more than doubled compared to untreated HGF. Crucially, the protein also exhibited increased resistance to the functional degradation caused by nitration, especially at the Y198 site. This enhanced effect was exclusively observed with LASSS; GSSSG did not produce similar improvements.

"This exceeded our expectations," commented Tatsumi. "We knew trisulfides had diverse biological functions, but we never expected that simply mixing HGF with LASSS would produce such a striking effect." He elaborated that the findings suggest LASSS may do more than just neutralize reactive molecules; it might directly interact with HGF, inducing a subtle structural modification. This could create a more potent form of HGF, which he termed 'Super HGF,' capable of binding more effectively to c-met and withstanding chemical damage.

To validate these findings in a living system, the researchers conducted experiments using mice models. Mice subjected to tail suspension, a procedure known to induce muscle atrophy, were treated with LASSS prior to the experiment. The results showed significantly lower levels of HGF nitration in the LASSS-treated group compared to the control group. The protective effect of GSSSG, however, remained negligible.

These outcomes indicate that the benefits of LASSS extend beyond isolated protein interactions and hold potential for practical application. While further studies, particularly involving aging animal models, are necessary to confirm safety and efficacy in vivo, the discovery offers a potential strategy for preserving muscle health. This could be beneficial for individuals experiencing prolonged inactivity due to illness, bed rest, or the natural aging process. The researchers posit that the effects of LASSS on HGF may be conserved across species, potentially benefiting both humans and companion animals.