Skeletal muscle often begins to deteriorate relatively early in the aging process. Over time, this can cause loss of strength, increased scarring, accumulation of fat within muscle tissue, and a decrease in fast-twitch fibers, which support fast, powerful movements.
Researchers led by Professor Ryuichi Tatsumi of the Faculty of Agriculture at Kyushu University have identified a molecule that could protect and enhance an important signal involved in muscle repair. The results were published on July 24, 2026, in Scientific Reports.
How the body activates muscle repair
The research focuses on hepatocyte growth factor, or HGF, a protein that helps initiate skeletal muscle repair. Under normal conditions, HGF remains inactive within the structural network surrounding muscle fibers.
When muscle tissue is injured or exposed to mechanical stimulation, HGF is released. It then binds to c met receptors on satellite cells, the stem cells responsible for maintaining and repairing skeletal muscle. This signal brings cells out of their dormant state, allowing them to multiply, mature, and help rebuild damaged muscle fibers.
Aging can alter this repair system. Previous investigations The team discovered that HGF can undergo a chemical modification known as nitration. During this process, a nitro group is added to two locations on the protein, Y198 and Y250. These sites are located in the same region that HGF uses to connect to c met.
After nitration occurs, HGF can no longer bind effectively to the receptor. The researchers compare the damaged protein to a rusty key that no longer fits its lock. This loss of function may be one of the underlying causes of muscle atrophy and reduced regeneration in older adults.
“HGF doesn’t necessarily go away as we age,” explains Tatsumi. “Rather, it can be chemically altered after it is made. That led us to wonder whether a compound with a strong antioxidant capacity could protect HGF, either by preventing nitration or compensating for the functional loss it causes.”
Sulfur-based antioxidant test
The scientists investigated two compounds with strong antioxidant properties: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS). Both are trisulfides, a class of molecules that contain three sulfur atoms connected in sequence.
These compounds have attracted increasing interest in pharmaceutical research due to their distinctive sulfur chemistry and their ability to participate in redox reactions.
Early experiments showed that both GSSSG and LASSS reduced nitration at the Y198 and Y250 sites in HGF. However, neither compound completely restored the protein’s ability to bind to its receptor.
The researchers then increased the molar ratio of HGF to trisulfide, going from 1:4000 to 1:8000.
LASSS creates a stronger HGF signal
The increased concentration produced an unexpected result. When HGF was mixed with LASSS, its ability to bind ac met increased to more than double that of untreated HGF. The protein also became more resistant to loss of function caused by nitration, particularly at Y198.
This improvement was observed only with LASSS. GSSSG did not produce the same effect.
“This exceeded our expectations,” says Tatsumi. “We knew that trisulfides had various biological functions, but we never expected that simply mixing HGF with LASSS would produce such a surprising effect.
“What this tells us is that LASSS does more than simply neutralize reactive molecules. It can interact directly with HGF and induce a subtle structural change, creating an improved form of ‘Super HGF’ that binds c-met more strongly and resists nitration.”
The findings suggest that LASSS may directly alter the structure of HGF in a beneficial manner. Instead of acting only as an antioxidant, the compound can create a more active form of the protein that connects more strongly with its receptor while resisting chemical damage.
Promising results in a mouse model
To determine whether the protective effect could also occur in living tissue, the team tested LASSS in mice with muscle atrophy caused by tail suspension.
Mice treated with LASSS before the procedure had significantly lower nitration levels than untreated mice. Once again, GSSSG did not provide measurable protection. These results indicate that the beneficial effects of LASSS are not limited to laboratory experiments with isolated proteins.
However, additional studies with aged animals will be needed to determine whether LASSS is safe and effective in vivo.
A possible strategy to preserve muscle
The discovery could support the development of new approaches to maintain muscle repair during aging, prolonged bed rest and other conditions that involve long periods of inactivity.
Researchers believe LASSS’s effects on HGF may apply to multiple species, including humans and companion animals such as cats and dogs. In the future, this approach could help people maintain strength, independence, quality of life, and a longer healthy life as they age.