Skeletal muscle often begins to deteriorate relatively early in the aging process. Over time, this can cause muscle weakness, increased scarring, accumulation of fat within muscle tissue, and a decrease in fast-twitch muscle fibers that support quick, powerful movements.
Researchers led by Professor Ryuichi Tatsumi of Kyushu University’s Faculty of Agriculture have identified a molecule that can protect and enhance key signals involved in muscle repair. The results will be announced on July 24, 2026. scientific report.
How the body activates muscle repair
The study focuses on hepatocyte growth factor (HGF), a protein that helps initiate skeletal muscle repair. Under normal conditions, HGF remains inactive within the structural network surrounding muscle fibers.
HGF is released when muscle tissue is injured or exposed to mechanical stimulation. It then binds to cmet receptors on satellite cells, the stem cells responsible for maintaining and repairing skeletal muscle. This signal releases cells from an inactive state, allowing them to proliferate and mature, and helps rebuild damaged muscle fibers.
Aging can disrupt this repair system. The team’s previous research found that HGF can undergo a chemical modification known as nitration. During this process, nitro groups are added to two positions on the protein, Y198 and Y250. These sites are located in the same area that HGF uses to connect with cmet.
When nitration occurs, HGF is no longer able to bind effectively to the receptor. Researchers liken the damaged protein to a rusty key that no longer fits. This loss of function may be one of the underlying causes of muscle weakness and reduced regeneration in older adults.
“HGF is not necessarily lost with age,” Professor Tatsumi explains. “Rather, HGF can be chemically altered after its formation, which led us to think that compounds with strong antioxidant capacity might protect HGF by preventing nitration or by compensating for the loss of function that HGF causes.”
Testing sulfur-based antioxidants
Scientists studied two compounds with powerful antioxidant properties: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS). Both are trisulfides, a type of molecule with three sulfur atoms bonded in series.
These compounds are of increasing interest in pharmaceutical research due to their unique sulfur chemistry and ability to participate in redox reactions.
Initial experiments showed that both GSSSG and LASSS reduced nitration at the Y198 and Y250 sites on 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 from 1:4000 to 1:8000.
LASSS produces a stronger HGF signal
Increasing the concentration yielded unexpected results. When HGF was mixed with LASSS, its binding capacity to cmet increased more than twice that of untreated HGF. The protein also had improved resistance to loss of function by nitration, particularly at Y198.
This improvement was only seen with LASSS. GSSSG did not have the same effect.
“This exceeded our expectations,” comments Tatsumi. “We knew that trisulfides have diverse biological functions, but we never expected that simply mixing HGF and LASSS would have such a pronounced effect.
“This suggests that LASSS does more than simply neutralize reactive molecules. It may interact directly with HGF and induce subtle conformational changes, creating an enhanced ‘super-HGF’ form that binds c-met more tightly and resists nitration.”
This finding suggests that LASSS may directly alter the structure of HGF in a beneficial manner. Rather than acting solely as an antioxidant, this compound may produce a more active form of the protein that binds more tightly to receptors while resisting chemical damage.
Promising results in mouse models
To determine whether this protective effect also occurs in living tissue, the researchers tested LASSS in mice that had developed muscle atrophy due to tail suspension.
Mice treated with LASSS before treatment had significantly lower nitration levels than untreated mice. Again, GSSSG provided no measurable protection. These results demonstrate that the beneficial effects of LASSS are not limited to laboratory experiments involving isolated proteins.
However, additional studies in older animals are needed to determine whether LASSS is safe and effective in vivo.
Possible strategies for preserving muscle
The findings could help develop new approaches to maintain muscle repair during aging, prolonged bed rest, and other conditions involving long periods of inactivity.
Researchers believe that the effects of LASSS 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 their physical strength, independence, and quality of life as they age, and extend their healthy lives.
