Improving Muscle Health in Older Adults with Urolithin A

This scientific summary is based on the scientific research article titled "Urolithin A, a Gut Microbiome Derived Metabolite Improves Mitochondrial and Cellular Health: Results from a Randomized, Placebo-controlled, Double-blind Clinical Trial (FS09-06-19)" by Anurag Singh et al., explores the potential benefits of Urolithin A (UA) for muscle health in older adults. As people age, mitochondrial function in skeletal muscles declines, contributing to muscle weakness and decreased physical capacity. Urolithin A, a metabolite produced by gut bacteria from ellagitannins found in foods like pomegranates, nuts, and berries, has shown promise in inducing mitophagy—a process that removes damaged mitochondria and promotes the formation of new, healthy ones. This study investigates UA's safety, bioavailability, and impact on mitochondrial biomarkers in elderly individuals, offering a novel nutritional intervention for age-related muscle decline.

As people age, their muscles often weaken. This can make it harder to do everyday things like walking, climbing stairs, or carrying groceries.

Keeping muscles strong is important for older adults to stay healthy and active. Scientists have been looking for ways to help, and one promising solution is Urolithin A (UA).

When mitochondria get old or damaged , they also stop producing energy. This is bad for muscle cells because muscles need a lot of energy to stay strong and function properly. As a result, when mitochondria aren't working well, our muscles weaken, making it harder to do physical activities.

Other factors, such as less physical activity, changes in hormone levels, and not eating enough protein, also weaken muscles with age. However, improving mitochondrial health is a key part of keeping muscles strong as we age.

Urolithin A helps our muscles stay strong by improving mitochondrial health. When UA is made in our bodies, a process called mitophagy starts. Mitophagy is like a cleaning service for our cells . It removes old and damaged mitochondria, making space for new, healthy ones. This is important because having healthier mitochondria means our cells can produce more energy.

Scientists first discovered this process in animals. They found that animals given UA had better mitochondrial health and improved muscle function. These findings were exciting, but scientists wanted to know if the same would be true for humans.

Recent studies, including the clinical study discussed here, have shown that UA also works in humans. The study found that taking UA improved the activity of genes related to mitochondrial function and lowered levels of certain substances in the blood, which indicated poor mitochondrial health. This means that UA helps keep mitochondria in good condition, which can help muscles stay strong and healthy as we age.

To see if UA helps humans, scientists conducted a study with older adults. The study had two parts:

• Part A: This part involved 24 healthy older adults who took a single dose of UA (either 250 mg, 500 mg, 1000 mg, or 2000 mg) or a placebo.
• Part B: This part involved 36 healthy older adults who took one of three doses of UA (250 mg, 500 mg, or 1000 mg) or a placebo every day for 28 days.

Participants took UA on an empty stomach. The scientists monitored their blood and muscle samples to see what happened. According to the research paper, "UA was administered orally, in fasting condition. Subjects were monitored for adverse events and safety parameters. Plasma and muscle biopsies were collected to investigate the effects of UA on the skeletal muscle transcriptome and on the metabolomics profile."

The study found some exciting results:

• Safety: UA was safe to use, with no serious side effects. The research states, "In both phases, there were no serious adverse events (SAE) recorded. No clinically significant changes were reported in a battery of safety tests."
• Bioavailability: UA was found in the blood and muscles, which means the body can use it effectively. The paper noted, "UA was bioavailable in human plasma and in the skeletal muscle."
• Mitochondrial Health: After taking UA, the participants had more activity in their mitochondrial genes, which means their cells were getting better at making energy. The study reported that "UA administration significantly up-regulated mitochondrial gene expression in the skeletal muscle."
• Lower Acylcarnitines: UA also helped lower certain substances in the blood called acylcarnitines. High levels of these can mean that mitochondria aren't working well. The research highlighted, "UA treatment... [led to] a dose-dependent decrease of acylcarnitines levels."

These results show that UA can help improve muscle health in older adults. By boosting mitochondrial function, UA might help people stay strong and active as they age. This could lead to better overall health and a higher quality of life.

The study concludes, "These results demonstrate a successful translation of the effects of UA on muscle mitochondria in elderly, and open the door to a new nutritional solution for managing age-related muscle decline."

Here's how older adults can get benefits from UA:

• Foods Rich in Ellagitannins: Eating pomegranates, nuts, and berries can help your body make UA.
• Future Supplements: Scientists are working on making UA supplements that people can take easily.
• Healthy Lifestyle: Eating a balanced diet and staying active are key to keeping muscles strong.

Urolithin A helps clean out old mitochondria and makes way for new, healthy ones, giving muscles more energy. This study shows that UA is safe and effective, opening new possibilities for better muscle health as we age.