Scientists in Switzerland discover that gut microbiome postbiotic, Urolithin A, may help combat muscle fatigue with aging

As we age, we often feel like we lack energy. But what if it was the other way around? What if it was a lack of energy that made us feel aged? That makes sense from a biochemical point of view. Low energy levels stop our muscles from working as well as they could. And the progressive loss of muscle function is a well-established feature of aging. So, logic suggests that if we can find more energy from somewhere, then we can keep our muscles working better for longer – and so curtail a fundamental feature of aging, even as we rack up the years.

And now scientists at the Swiss Federal Institute of Technology Lausanne (EPFL) and life-science company Amazentis believe they have found a way to do so with a highly pure Urolithin A supplement called Mitopure.

“We have identified a breakthrough molecule that activates an essential cellular renewal pathway,” says Chris Rinsch, cofounder and CEO of Amazentis. “It repairs and renews the energy factories inside our cells, translating to improved muscle strength and endurance.”

Extra energy does not usually come easily, especially later in life. There is no free lunch, and if there were, then eating the extra calories would probably cause more health problems. So, to find extra energy, instead scientists need to make better use of the food and nutrition we already eat. And for that, they need to look inside our cells.

Converting food into energy that muscles can use is the job of cellular mitochondria. Self-contained sacs of biochemical reactions — cells-within-cells – mitochondria generate adenosine triphosphate (ATP), a chemical tissues across the body use to maintain life. Muscle cells, as one would expect, have a high demand for ATP and so carry more mitochondria than most.

Muscles work mitochondria hard, and these cellular power stations wear out quickly. As they do so, their ATP yield drops. Left unaddressed, this ATP shortage would quickly drag down muscle performance, so cells have an ongoing process to identify and replace underperforming mitochondria. Central to this mitochondrial maintenance is the selective programmed destruction of worn-out mitochondria, a process called mitophagy.

A series of recent studies have correlated prominent signs of aging with impaired mitophagy, including loss of muscle function, cognitive decline, and memory loss.

“It’s become clear in recent years that declining levels of mitochondrial health and mitophagy play a central role in aging,” says Johan Auwerx, a medical doctor and cellular biologist at the EPFL, who won the prestigious Marcel Benoist Prize in 2016. “And understanding how we can recharge mitophagy has opened up new possibilities to intervene and support vitality and health as we age.”

Much research on how to boost mitophagy focuses on a chemical called Urolithin A. It’s an unusual molecule – Urolithin A is only produced as a by-product when gut bacteria digest specific ingredients found in pomegranates and a few other foods. Importantly, not everybody has the right combination of gut bacteria to perform this conversion. That means about 60 percent of people can’t make and benefit from naturally-produced Urolithin A, however many pomegranates they eat. And at the moment there is no simple test that can distinguish these people.

Are these Urolithin A non-producers missing out? Experiments in both animals and people suggest they are.

Some of the earliest studies were performed on a tiny nematode worm called Caenorhabditis elegans. More usually found in soil, these millimeter-long worms offer scientists a way to model aging processes in humans. That’s because they share many of the same genes and show the same kinds of age-related decline. And, with a lifespan of only a few weeks, experiments to investigate aging processes finish much more quickly.

Some of these studies have shown impressive results. Feeding worms with Urolithin A can extend their lifespan by about 45 percent. How? By analyzing which genes were expressed in the worms, researchers have traced the likely effect to increased mitophagy. The Urolithin A helped to protect the worms’ mitochondrial function, and this delayed some key processes associated with aging.

Processes such as muscle performance for example: Young worms fed urolithin A showed improved integrity of muscle fibers, while in old worms the molecule made them more active and also increased levels of so-called pharyngeal pumping, which the organisms rely on to feed.

Similar results have been seen in other animals. Urolithin A improves muscle function in mice and is associated with better aerobic performance, such as allowing the animals to run for 40 percent longer on a treadmill. Just like the mice, patterns of gene expression show that the benefits flow from improved mitophagy. “Urolithin A is the only known molecule to activate mitophagy that has been shown to be safe and effective in rigorous placebo-controlled human clinical studies focused on muscle health” Auwerx says.

We have been here before of course. Anti-aging science is littered with promising results from animals that could not be repeated in people. It’s early days, but Urolithin A seems different. Scientists at Amazentis – a life science company that operates from the EPFL innovation campus — have carried out several human clinical studies, and the results signal that urolithin A does offer benefits.

To standardize dosing and to make the results more reliable, the company has synthesized a highly pure Urolithin A supplement called Mitopure. Amazentis has run a number of clinical trials. The most recent randomized, double-blind, placebo-controlled clinical trial – the gold standard of scientific studies – in healthy, older adults, showed that daily consumption of 1000mg Mitopure for two months led to a statistically significant improvement muscle endurance. The study published in the JAMA Network Open showed that after two months the number of muscle contractions until fatigue increased from baseline by ~17% (p=0.05 compared to placebo) for the leg muscle and 26% (p<0.01 compared to placebo) for the hand muscle for the group receiving Mitopure compared to 2% and 3% increase for placebo.

Importantly, because 60 to 70 percent of people lack the necessary gut bacteria to convert raw ingredients in their diet into Urolithin A, supplementation is the only way to help ensure people will get a precise clinically tested dose. Even for those who can naturally produce urolithin A, studies show that natural sources such as pomegranate juice offer an inconsistent and so unreliable source. A separate randomized clinical trial conducted by Amazentis in healthy adults showed that 500mg of the Mitopure supplement delivers six times as much urolithin A compared with a large glass of pomegranate juice. Amazentis was the first company in the world to commercialize a Urolithin A supplement under it’s Timeline Nutrition brand powered by Mitopure.

“These results show that a nutritious diet just isn’t enough. Without the right gut microbiome, people won’t get all the health benefits, and that creates a huge gap in our current approaches. One solution is direct supplementation. It can solve the non-producer problem and help everyone to access these important anti-aging benefits.” says chief medical officer of Amazentis, Anurag Singh MD, PhD.