Skeletal muscle often begins to deteriorate relatively early in the aging process. Over time, this can cause loss of strength, increased scarring, fat buildup within muscle tissue, and a decline in fast twitch fibers, which support rapid and powerful movements.
Researchers led by Professor Ryuichi Tatsumi of Kyushu University’s Faculty of Agriculture 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 the repair of skeletal muscle. 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 attaches to c met receptors on satellite cells, the stem cells responsible for maintaining and repairing skeletal muscle. This signal brings the cells out of their inactive state, allowing them to multiply, mature, and help rebuild damaged muscle fibers.
Aging can disrupt this repair system. Previous research from the team found 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 HGF uses to connect with c met.
After nitration occurs, HGF can no longer attach effectively to the receptor. The researchers compare the damaged protein to a rusted key that no longer fits its lock. This loss of function may be one of the underlying causes of muscle wasting and reduced regeneration in older adults.
“HGF is not necessarily missing as we age,” explains Tatsumi. “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.”
Testing Sulfur Based Antioxidants
The scientists investigated two compounds with strong antioxidant properties: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS). Both are trisulfides, a class of molecules containing three sulfur atoms connected in sequence.
These compounds have attracted growing interest in pharmaceutical research because of 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 on HGF. However, neither compound fully restored the protein’s ability to bind to its receptor.
The researchers then increased the molar ratio of HGF to trisulfide, moving from 1:4000 to 1:8000.
LASSS Creates a Stronger HGF Signal
The higher concentration produced an unexpected result. When HGF was mixed with LASSS, its ability to bind to c met rose to more than twice that of untreated HGF. The protein also became more resistant to the loss of function caused by nitration, particularly at Y198.
This improvement was seen only with LASSS. GSSSG did not produce the same effect.
“This exceeded our expectations,” comments Tatsumi. “We knew trisulfides had diverse biological functions, but we never expected that simply mixing HGF with LASSS would produce such a striking effect.
“What this tells us is that LASSS does more than simply neutralize reactive molecules. It may interact directly with HGF and induce a subtle structural change, creating an enhanced ‘Super HGF’ form that binds c-met more strongly and resists nitration.”
The findings suggest that LASSS may directly alter the structure of HGF in a beneficial way. Rather than acting only as an antioxidant, the compound may 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 levels of nitration 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 involving isolated proteins.
However, additional studies involving aging animals will be required to determine whether LASSS is safe and effective in vivo.
A Possible Strategy for Preserving Muscle
The discovery could support the development of new approaches for maintaining muscle repair during aging, extended bed rest, and other conditions that involve long periods of inactivity.
The researchers believe the effects of LASSS on HGF may apply across multiple species, including humans and companion animals such as cats and dogs. In the future, the approach could potentially help people maintain strength, independence, quality of life, and a longer healthy lifespan as they grow older.
