Japanese Scientists Discover Molecule That Could Help Protect Muscle Repair System Against Aging

Muscle strength and the body’s ability to repair damaged tissue can begin declining earlier than many people realise. As aging progresses, muscles may accumulate fat and scar tissue while losing specialised fibres responsible for fast, powerful movements. These changes can gradually affect mobility, make everyday physical activities more challenging and reduce independence.

Now, researchers in Japan have identified a promising molecule that could help preserve the body’s natural muscle regeneration process. Laboratory experiments suggest that the compound can strengthen an important biological signal involved in muscle repair, improving its ability to bind to a key cellular receptor by more than twofold.

The research was led by Professor Ryuichi Tatsumi from the Faculty of Agriculture at Kyushu University. Published in the journal Scientific Reports, the findings point towards a potential new strategy for addressing the cellular changes that make aging muscles less effective at repairing themselves.

How Aging Affects The Body’s Natural Muscle Repair Mechanism

Skeletal muscles, which connect to bones, play an essential role in everyday movements such as walking, lifting objects and maintaining posture. Despite experiencing regular wear and tear, these muscles have an inherent ability to regenerate and repair damaged tissue.

This regenerative process relies heavily on specialised stem cells called satellite cells. Located alongside muscle fibres, these cells typically remain dormant until an injury or other physical stimulus signals the need for repair.

Once activated, satellite cells multiply and develop into muscle cells, helping rebuild damaged muscle tissue.

One of the key proteins responsible for initiating this process is hepatocyte growth factor (HGF). Although its name suggests a primary association with the liver, HGF also performs important functions in skeletal muscle regeneration by activating satellite cells.

Under normal circumstances, HGF remains stored in the supportive material surrounding muscle fibres. When muscles experience damage or mechanical stimulation, including movement and stretching, the protein is released.

It then attaches to a receptor known as c-met, which is present on the surface of satellite cells. This interaction activates the dormant stem cells, prompting them to multiply, mature and contribute to muscle repair.

However, researchers have found that this signalling mechanism can become less effective as the body ages, potentially limiting its ability to regenerate muscle tissue.

Chemical Changes Could Be Interfering With Muscle Regeneration

Previous research conducted by Tatsumi’s team identified a chemical process called nitration that can interfere with HGF’s normal functioning.

Nitration occurs when a chemical group known as a nitro group attaches to specific locations on a protein. This modification can alter the protein’s structure and affect how effectively it performs its biological function.

The researchers identified two particularly important locations on HGF, known as Y198 and Y250. Both are situated within the region responsible for binding with the c-met receptor.

When nitration occurs at these locations, HGF becomes less effective at connecting with c-met. This weakens the molecular communication required to activate satellite cells and initiate muscle regeneration.

The discovery offers a possible explanation for why aging muscles gradually lose some of their ability to recover from damage. Even when the body continues producing HGF, chemical modifications may prevent the protein from delivering its regenerative signal effectively.

Over time, this disruption could contribute to age-related muscle wasting and a decline in the body’s natural tissue-repair capabilities.

“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.”

The researchers are investigating whether an antioxidant compound could help preserve HGF’s activity and restore its ability to activate the cellular mechanisms responsible for muscle repair. Their findings could eventually contribute to new approaches for maintaining muscle health, strength and physical independence with age.