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Writer's pictureKen Ecott

Compound with anti-aging effects passes human trial


Pomegranates slow down the ageing process by prompting cells to recycle and rebuild themselves, a study shows.

Are pomegranates really the super-food that will counteract ageing? Scientists have discovered that a molecule in pomegranates, transformed by microbes in the gut, enables muscle cells to protect themselves against one of the major causes of aging.

Since ageing is a key driver of many diseases, targeting that process could be a handy catch-all for treating a range of diseases and improving quality of life for pretty much everybody. Researchers at EPFL have now reported a new step towards that goal, with human clinical trials of a fruit-derived compound showing promise in slowing mitochondrial aging in elderly patients, with no side effects found.

A compound called urolithin A (UA) was the focus of the study, after previous experiments with it showed promise in extending the lifespans of worms and mice. The compound appears to fight ageing by improving the function of mitochondria – the energy-producing part of a cell – in a way similar to the benefits of exercise. While it's not found naturally in any known food, biomolecules in fruits like pomegranates and raspberries do break down into UA in the human gut.

However, humans can only benefit from the anti-ageing chemical if they possess the right sort of bacteria in their gut. The microbes are needed to convert the fruit's raw ingredient into urolithin A.

For this study, the team synthesised the UA compound, and administered it in various dose sizes to a group of 60 elderly test subjects. These people all lived fairly sedentary lifestyles but were in good health at the time of the experiment. The test was run to determine the safety of the compound, as well as how well it may work.

In the first round of tests, the researchers gave some participants a single oral dose of UA, between 250 and 2,000 mg. No side effects were spotted when this test group was compared to a control group. Next up, the team tested the safety and effectiveness of the compound over a 28-day period. The subjects were split into four groups, each receiving a different daily oral dose of UA: 250 mg, 500 mg, 1,000 mg, and a control group which received a placebo.

Again, none of the subjects were seen to exhibit any side effects after prolonged use. The researchers checked for biomarkers of UA in plasma samples taken from the patients, and found them to be present at all doses.

Importantly, the team found that at doses of 500 and 1,000 mg, the gene expression of mitochondria in skeletal muscle cells was affected, stimulating biogenesis in the same way exercise does.

"These latest findings, which build on previous pre-clinical trials, really crystallise how UA could be a game-changer for human health," says Johan Auwerx, an author of the study.

Over time, mitochondria become worn out and damaged, mitophagy becomes less efficient and cells end up cluttered with old, poorly functioning mitochondria. This harms the health of many organs and tissues and weakens muscles.

The build-up of dysfunctional mitochondria is associated with many conditions of ageing, such as Parkinson's disease.

The hope is that treatment with UA could slow down or even reverse the loss of skeletal muscle mass that naturally occurs with age, as well as the weakening of other tissues.

This latest study is one of many recent anti-ageing studies to focus on mitochondria. Scientists have found ways to increase lifespan in fruit flies by clearing out damaged mitochondria, and investigated the positive effect fasting appears to have on these little power plants.

An EPFL spin-off named Amazentis is planning to bring UA products to market as quickly as possible, but further work will no doubt need to be done first.

The new research was published in the journal Nature Metabolism.

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