Researchers have discovered a sulfur-based compound, LASSS, that significantly boosts the muscle repair process in aging individuals, potentially combating muscle loss.
New Delhi, India Jul 24, 2026 ALN: 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. This deterioration is not only a cosmetic concern but also poses significant risks, as muscle strength is closely linked to overall physical , mobility, and the ability to perform daily activities.
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. This research is particularly relevant as the global population ages, and the prevalence of age-related muscle loss, known as sarcopenia, increases. Sarcopenia is associated with a range of negative outcomes, including falls, fractures, and decreased quality of life.
The research focuses on hepatocyte growth factor, or HGF, a protein that helps initiate the repair of skeletal muscle. Under normal physiological conditions, HGF remains inactive within the structural network surrounding muscle fibers. This inactivation is crucial for maintaining muscle homeostasis; however, when muscle tissue is injured or exposed to mechanical stimulation, HGF is released from its inactive state. It then attaches to c-met receptors on satellite cells, the stem cells responsible for maintaining and repairing skeletal muscle.
This signaling process brings the satellite cells out of their dormant state, allowing them to multiply, mature, and help rebuild damaged muscle fibers. This mechanism is vital for muscle recovery following injury or stress. However, aging can disrupt this repair system, leading to inefficient muscle regeneration and contributing to the overall decline in muscle mass and function.
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 specific locations on the protein, Y198 and Y250. These sites are located in the same region HGF uses to connect with c-met, which is crucial for its functionality. 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, highlighting the importance of maintaining the integrity of HGF as we age.
"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." This insight underscores the potential for pharmacological interventions that could target the biochemical pathways involved in muscle repair.
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, which are critical for maintaining cellular and function.
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. This finding suggests that while both compounds can mitigate some of the damage caused by nitration, they may not completely reverse the functional impairments associated with aging and muscle repair.
In a pivotal moment of the research, the team increased the molar ratio of HGF to trisulfide, moving from 1:4000 to 1:8000. This adjustment was made to assess whether higher concentrations of the compounds could yield better results in terms of HGF functionality.
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 the Y198 site. This significant enhancement in binding affinity indicates that LASSS may play a crucial role in not only protecting HGF but also augmenting its signaling capacity.
This improvement was seen only with LASSS; GSSSG did not produce the same effect. The specificity of LASSS in enhancing HGF functionality raises intriguing questions about the molecular mechanisms at play. "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." This finding opens new avenues for research into how specific compounds can modulate protein function and potentially lead to therapeutic strategies for age-related muscle decline.
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, a model that simulates the effects of prolonged inactivity. 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 but also translate to more complex biological systems.
However, additional studies involving aging animals will be required to determine whether LASSS is safe and effective in vivo. Understanding the long-term effects and potential side effects of LASSS treatment will be critical before considering any clinical applications in humans. It is essential to establish a comprehensive safety profile, as well as to explore the optimal dosing strategies that would maximize therapeutic benefits while minimizing risks.
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. As the global population ages, the implications of this research could be profound. Strategies that effectively preserve muscle mass and function could lead to improved outcomes for older adults, reducing the burden of age-related diseases and enhancing overall quality of life.
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 lifespan as they grow older. As research progresses, the hope is to translate these findings into practical interventions that could be implemented in clinical settings, ultimately benefiting a wide range of patients suffering from muscle degeneration.
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