Researchers at Kyushu University have identified a compound that may help protect the repair signals muscles need to stay strong as people age. The finding offers a new way of looking at age-related muscle loss, which is common but not necessarily inevitable.
Muscle mass can decline about 8% per decade after age 30 if not actively supported. Many people accept this as a normal part of aging. However, a growing body of research suggests the problem is not simply that muscles waste away. Instead, muscles lose their ability to repair themselves. The internal signal that tells muscles to start repairing becomes chemically damaged over time.
At the center of the muscle repair system is a protein called hepatocyte growth factor, or HGF. This protein acts as a wake-up call for the body’s built-in repair crew. In healthy muscle, HGF sits in the supportive tissue surrounding muscle fibers. When muscle is injured or stressed, HGF is released and travels to stem cells embedded in the muscle tissue. Once it attaches to those stem cells, it activates them, prompting them to multiply and repair damaged fibers.
According to the study, the issue with aging muscle is not that HGF disappears. Instead, HGF undergoes a chemical change called nitration. This process alters the part of the protein responsible for attaching to muscle stem cells. The researchers compare HGF to a key that fits a specific lock. Nitration causes corrosion to build up on the teeth of that key. The key is still there, but it no longer fits. When this process stalls, muscle fibers begin to weaken, scar tissue and fat accumulate, and fast-twitch fibers slow down.
Testing sulfur-based compounds
The Kyushu University team searched for a compound that could prevent this chemical damage or compensate for it. They focused on two sulfur-based molecules known for their antioxidant properties: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS). Both belong to a class of compounds called trisulfides, which have drawn interest for their potential therapeutic applications.
In early experiments, both compounds reduced the chemical damage to HGF. Restoring the protein’s ability to bind to muscle stem cells proved more difficult, until the researchers adjusted the ratio of HGF to trisulfide. At a higher concentration, something unexpected happened with LASSS. Rather than simply protecting HGF from damage, LASSS appeared to enhance it. When combined with a larger amount of LASSS, HGF’s ability to bind to muscle stem cells increased more than two-fold compared with untreated HGF. It also became more resistant to chemical damage. GSSSG showed no such effect.
The researchers believe LASSS may interact directly with HGF and induce a subtle structural change, effectively creating a more powerful and resilient form of the protein. The team described it as a “Super HGF,” because it was not just a partial restoration of function but a full upgrade.
Testing in living tissue
To see whether the effect held up outside of a controlled lab setting, the team tested LASSS in a mouse model of muscle atrophy. Mice pretreated with LASSS showed significantly less chemical damage to HGF compared with untreated animals. GSSSG again showed no protective effect. Studies like this are often first conducted in mice because they share over 95% of their genes with humans and are easier to observe. Further studies need to be conducted in aging animals and eventually humans to confirm if LASSS is safe and effective over time. The mouse model provides encouraging evidence that LASSS’s effects are not limited to test tubes.
Muscle loss with age affects a significant portion of older adults and is closely linked to reduced independence, increased fall risk, and lower quality of life. Most current approaches focus on resistance training and protein intake. Research like this points to a molecular layer of the problem that these lifestyle interventions alone may not fully address. If LASSS or similar compounds can be developed into safe, effective therapies, they could offer a new tool for preserving muscle repair capacity during aging, prolonged bed rest, or other conditions that accelerate muscle decline. The researchers also note that HGF’s role in muscle repair is likely conserved across species, meaning the findings could eventually benefit companion animals like cats and dogs.
This research is new, and while this compound will not be available at pharmacies any time soon, the mechanism it highlights is important for understanding age-related muscle loss. The assumption has been that muscles wear out over time. It may actually be a matter of a repair signal being chemically blocked so it can no longer do its job. The discovery that a compound can not only protect that signal but amplify it opens a new world of ways to preserve muscle strength and function later in life.
