Researchers in Japan have identified a potent antioxidant compound that could help preserve muscle strength as people age, by protecting and even enhancing a key protein involved in muscle repair. The work offers an intriguing new direction for tackling age-related muscle loss, known as sarcopenia.
The research, published in Scientific Reports, focuses on hepatocyte growth factor, or HGF, a protein that activates muscle stem cells needed for regeneration after injury or disuse. Scientists at Kyushu University found that a compound called lipoic acid trisulfide, or LASSS, could protect HGF from damaging chemical changes and, at higher concentrations, even enhance its ability to interact with muscle stem cells.
As we grow older, many biological systems become less efficient, including the body’s ability to repair damaged muscle fibers. Previous studies from Kyushu University showed that HGF is not necessarily reduced in older muscles, but it can be chemically damaged. Over time, HGF undergoes nitration, a modification that weakens its ability to signal muscle stem cells, undermining the body’s capacity to maintain healthy muscle tissue.
How nitration disrupts muscle repair
Nitration occurs when reactive nitrogen molecules attach to certain amino acids in proteins, changing their structure and function. In the case of HGF, this process interferes with its binding to a receptor called c-met on muscle stem cells, a step that is vital for muscle regeneration.
The new research set out to determine whether strong antioxidants could shield HGF from nitration or reverse its damaging effects. The team focused on sulfur-rich molecules called trisulfides, known for their ability to neutralize reactive species inside the body.
Two compounds were tested: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS). Both carry three linked sulfur atoms, which makes them highly reactive antioxidants able to intercept harmful molecules before they modify crucial proteins like HGF.
A surprising “super HGF” effect
In lab experiments, both GSSSG and LASSS successfully reduced nitration at two vulnerable sites on the HGF protein. However, simply limiting nitration was not enough to fully restore HGF’s interaction with muscle stem cells at first, suggesting the effect was only partial.
When researchers increased the concentration of these compounds, LASSS produced a striking result. Not only did it block nitration damage more effectively, it also doubled HGF’s ability to bind to its c-met receptor, boosting the key signal required for muscle repair.
The team believes LASSS is doing more than just acting as a shield against reactive molecules. They suggest the compound may interact directly with HGF, subtly altering its structure to form what they describe as an enhanced “super HGF” that is both more resilient to nitration and better at activating muscle stem cells.
Early tests in muscle atrophy models
To see whether these promising lab findings would hold up in living tissue, the scientists turned to mouse models of muscle atrophy caused by disuse. These models mimic conditions such as immobilization, extended bed rest or microgravity exposure, which are known to trigger muscle wasting.
In these experiments, LASSS reduced nitration of HGF in the muscles of affected mice, suggesting it can preserve the protein’s function under stress. While the study did not yet evaluate long-term outcomes like sustained strength or mobility, it supports the idea that LASSS can protect the HGF repair pathway in vivo.
The next phase will involve testing LASSS in older animals and over longer timeframes to determine whether it can meaningfully slow or reverse age-related muscle decline. Safety, optimal dosing and delivery methods would also need to be clarified before any human trials could be considered.
Implications for aging and frailty
Sarcopenia, the gradual loss of muscle mass and strength, can begin as early as the 30s and accelerates after about age 60. It contributes to frailty, mobility problems and a higher risk of falls, fractures and loss of independence in later life, making it a major public health concern.
Current strategies to combat sarcopenia focus on exercise, adequate protein intake and managing chronic conditions, with relatively few targeted drug options. A therapy that protects or enhances HGF activity could potentially complement lifestyle measures and help maintain muscle function in older adults.
The researchers also see possible applications beyond normal aging. Conditions such as prolonged hospitalization, chronic illness, cancer treatments or neurological disorders can all cause muscle wasting, and an HGF-supporting compound like LASSS might one day be explored as an adjunct in those settings.
Experts caution that the findings are still at an early, preclinical stage, and many experimental therapies fail to translate from mouse models to humans. Nonetheless, the study highlights HGF nitration as a promising target and positions trisulfide antioxidants as a novel class of candidates for future muscle-preserving interventions.
Further independent research will be needed to confirm these results, test safety and understand precisely how LASSS modifies HGF. If those hurdles can be overcome, the discovery could add a new tool to the emerging toolkit aimed at extending not just lifespan, but healthy, active years in older age.
