‘Exceeded Our Expectations’: One Antioxidant Could Be Key to Keeping Aging Muscles Strong

There are many biological processes that naturally slow down or falter as we age, and a growing number of studies are looking at ways to interrupt that decline – to keep us living healthier for longer.

One of the ways old age affects the body is via changes to hepatocyte growth factor (HGF), a protein that helps activate muscle repair.

A few years ago, researchers from Kyushu University in Japan discovered that HGF undergoes a damaging chemical process called nitration as the years tick by, breaking the key muscle repair signal.

Could there be some way to protect HGF from this age-related alteration? That was the question the team sought to answer next.

In a new study, published in Scientific Reports, they tested two compounds designed to counter the effects of nitration via antioxidants – protective molecules that intercept the sabotaging chemical chain reaction.

“HGF is not necessarily missing as we age,” says biologist Ryuichi Tatsumi, from Kyushu University.

“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.”

Two sulfur-based compounds known for being powerful antioxidants were selected, glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS).

Both are classed as trisulfides, with three consecutively linked sulfur atoms – that’s what makes them highly reactive antioxidants.

In chemical binding studies, both GSSSG and LASSS were shown to effectively suppress nitration at two key vulnerable spots on the protein. However, the HGF links to the stem cells required for muscle repair weren’t sufficiently restored.

When the researchers upped the concentration of the compounds, LASSS stood out: Not only did it block nitration damage, it also made the protein twice as effective at connecting with the cells (via a receptor called c-met) that muscle repair processes rely on.

“This exceeded our expectations,” says 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.”

Next, the researchers used mouse models of muscle atrophy to test LASSS further. The experiments showed that the compound was indeed effective at reducing nitration induced by muscle disuse.

This still needs to be tested and verified in human muscles of course, but the early signs here are promising: a way of chemically reinforcing and supercharging the muscle-building HGF function that wanes in effectiveness with old age.

“The present work encourages additional in vivo research on the potential application of LASSS in extracellular HGF nitration-dysfunction during aging,” write the researchers in their published paper.

“Further exploration could lead to strategies for its use in age-related atrophy and impaired regeneration.”

The researchers are fairly confident that the impacts of LASSS on HGF will apply broadly across humans and other animals, and that there will be a wide range of possible uses too – not just maintaining health in old age, but also managing other situations where muscles can start to waste away, such as extended illnesses.

Sarcopenia is the technical term for age-related muscle loss, which can start from your 30s and tends to accelerate from your 60s. It leads to difficulties common in senior citizens, including problems walking and a higher risk of falls and accidents.

Related: Your Daily Rhythms May Help Slow Biological Aging, Study Suggests

Now we may have one way of helping the body resist that decline.

The next steps will be to run studies over longer periods of time to see how changes develop, and to test the LASSS compound in older mice, which wasn’t done here.

“This knowledge now opens novel ways to improve interventions that could combat age-related muscle atrophy and impaired regeneration with fibrosis and fat infiltration (including sarcopenia and frailty),” write the researchers.

The research has been published in Scientific Reports.