New Compound Could Help Aging Muscles Repair Themselves

A new sulfur-based compound might help aging muscles stay strong. It works by boosting a key signal that helps muscles repair themselves.

Researchers found that aging muscles don't necessarily lose their repair signals. Instead, these signals can get chemically damaged and stop working. This new compound seems to protect one important repair protein and helps it bind better to muscle stem cells.

This discovery could lead to new ways to treat muscle loss. This includes muscle loss from aging, not being active, or long periods of bed rest. However, these findings are still early. They come mostly from lab tests and studies in mice, not human trials.

Skeletal muscle is very affected by aging. It can slowly lose strength and flexibility as scar tissue and fat build up between its fibers. Fast-twitch fibers, which create quick, powerful movements, are often hit the hardest.

How Muscle Repair Signals Get Damaged

Professor Ryuichi Tatsumi and his team at Kyushu University looked into why muscles decline with age. Their study, published in Scientific Reports, focused on a protein called hepatocyte growth factor, or HGF.

HGF is important for muscle repair. It starts the repair process by activating satellite cells. These are stem cells found next to muscle fibers.

HGF is usually stored in the material around muscle fibers. Exercise or injury releases it. Then, HGF connects with c-met receptors on dormant satellite cells. This makes the cells wake up, multiply, mature, and help repair or grow muscle fibers.

This repair system becomes less effective with age. Tatsumi's team previously found that HGF can undergo nitration. This is a chemical change caused by reactive molecules in the body. During nitration, nitro groups attach to two spots on the HGF protein, Y198 and Y250.

These spots are crucial because they help HGF bind to c-met. Nitration can change this area, making the connection weaker or preventing it. The HGF protein might still be there, but it can't send its repair signal properly.

This damage seems to build up especially in fast-twitch muscle fibers. This might explain why these powerful fibers are lost more often as we age. HGF also helps control cells that cause scarring and fat buildup. So, a damaged HGF could contribute to several problems in aging muscles.

A Compound That Boosts Repair

Professor Tatsumi explained that HGF isn't missing as we age. Instead, it gets chemically changed after it's made. This led the team to wonder if a strong antioxidant could protect HGF. It might do this by preventing nitration or by making up for the lost function.

The researchers tested two sulfur-based antioxidants: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS). Both are trisulfides, which have three sulfur atoms linked together. Their unique chemistry allows them to take part in redox reactions, making them interesting for drug research.

Initial tests showed some success. Both compounds reduced nitration at Y198 and Y250. However, neither fully brought back HGF's ability to bind to c-met. The team then increased the amount of trisulfide compared to HGF.

At the higher ratio, LASSS did something unexpected. HGF mixed with LASSS bound to c-met more than twice as strongly as untreated HGF. It also became more resistant to the loss of function caused by nitration, especially at Y198. GSSSG did not show the same improvement.

Tatsumi noted this was beyond their expectations. He said they knew trisulfides had many biological roles, but they didn't expect simply mixing HGF with LASSS to have such a strong effect.

This suggests that LASSS does more than just fight reactive molecules. It might directly interact with HGF and cause a small change in its structure. This creates an improved "Super HGF" that binds to c-met more strongly and resists nitration.

A New Approach to Muscle Decline

The team then checked if this protective effect would happen in living muscle. They used mice that had their tails suspended, which mimics muscle loss from not moving.

Mice treated with LASSS beforehand had much less HGF nitration than untreated mice. GSSSG again did not offer the same protection. This supports the idea that the effect depends on the specific interaction between LASSS and HGF, not just its antioxidant power.

This research points to a new way to tackle muscle decline. Instead of replacing a missing growth factor, a future treatment could protect an existing repair signal from age-related damage. It could also improve its ability to activate muscle stem cells.

Since similar forms of HGF exist in humans and other mammals, the researchers believe this mechanism could eventually help people. It could also help pets like cats and dogs. This could preserve their movement, independence, and quality of life as they age or during long periods of inactivity.

Deep Dive & References

Enhanced HGF with increased receptor affinity and nitration-dysfunction resistance through interaction with lipoic acid trisulfide - Scientific Reports, 2026