The Fountain of Youth Molecule from Pomegranate Discovered

    Superfoods are unfortunately a bit of a misnomer, as they won’t actually give you any superpowers; but over the years they have been touted as providing extreme nutritional and health benefits. For instance, pomegranates have been marketed as supplying consumers with superior antioxidant levels and antiaging properties. Yet up until now, scientific proof has been weak at best. However, new research from scientists at the Swiss Federal Institute of Technology in Lausanne (EPFL) and company Amazentis has led to the discovery of a molecule in pomegranates—transformed by microbes in the gut—that enables muscle cells to protect themselves against one of the principal causes of aging.

    The investigators have described their findings from their study, which was performed on nematodes and rodents, as nothing short of amazing. Moreover, human clinical trials are currently underway using the knowledge they learned from the recently published study.

    As cells age, they struggle increasingly to recycle their mitochondria—the organelle responsible for producing the primary source of power in the cell. As the mitochondria are no longer able to do their job, they begin to accumulate in the cell and they affect the health of many tissues, including muscles, which gradually weaken over the years. Moreover, a buildup of dysfunctional mitochondria is also suspected of playing a role in other diseases of aging, such as Parkinson’s disease.

    In the new study, the Swiss researchers identified a molecule that, by itself, was able to re-establish the cell’s ability to recycle the components of the defective mitochondria—urolithin A (UA).

    “It’s the only known molecule that can relaunch the mitochondrial cleanup process, otherwise known as mitophagy,” explained co-author Patrick Aebischer, M.D., professor and president of EPFL. “It’s a completely natural substance, and its effect is powerful and measurable.”

    The investigators initiated their study by testing their hypothesis out on the model genetic organismCaenorhabditis elegans—a favorite test subject among aging experts because after just 8–10 days it’s already considered elderly. Amazingly, the lifespan of worms exposed to UA increased by more than 45% compared with the control group.

    While the initial results were extremely encouraging, the research team decided to test the molecule on animals that have more in common with humans. In the rodent studies, like with C. elegans, a significant reduction in the number of mitochondria was observed, indicating that a robust cellular recycling process was taking place. Older mice, around 2 years of age, showed 42% better endurance while running than equally old mice in the control group.

    “We identified UA as a first-in-class natural compound that induces mitophagy both in vitro and in vivofollowing oral consumption,” the authors wrote. “In C. elegans, UA prevented the accumulation of dysfunctional mitochondria with age and extended lifespan. These effects translated to rodents, where UA improved exercise capacity in two different mouse models of age-related decline of muscle function, as well as in young rats. Our findings highlight the health benefits of UA and its potential application in strategies to improve mitochondrial and muscle function.”

    The findings from this study were published recently in Nature Medicine in an article entitled “Urolithin A Induces Mitophagy and Prolongs Lifespan in C. elegans and Increases Muscle Function in Rodents.”

    “Species that are evolutionarily quite distant, such as C. elegans and the rat, react to the same substance in the same way,” noted senior study author Johan Auwerx, M.D., Ph.D., professor at EPFL. “That’s a good indication that we’re touching here on an essential mechanism in living organisms.”

    While the results from this study are remarkable, don’t rush out to your supermarket just yet to stock up on pomegranates. It’s worth noting that the fruit itself doesn’t contain the miracle molecule, but rather its precursor. That molecule is converted into UA by the microbes that inhabit the intestine. Because of this, the amount of UA produced can vary widely, depending on the species of animal and the flora present in the gut microbiome. Moreover, some individuals don’t produce any at all, and if you happen to be one of the unfortunate ones, it’s possible that pomegranate juice won’t do you any good.

    For those without the right microbes in their guts, however, the scientists are already working on a solution. The study’s co-authors founded a start-up company, Amazentis, which has developed a method to deliver finely calibrated doses of UA and is currently conducting its first clinical trials, testing the molecule on humans in European hospitals.

    “Precursors to urolithin A are found not only in pomegranates but also in smaller amounts in many nuts and berries,” remarked co-author Chris Rinsch, Ph.D., CEO of Amazentis. “Yet for it to be produced in our intestines, the bacteria must be able to break down what we’re eating. When, via digestion, a substance is produced that is of benefit to us, natural selection favors both the bacteria involved and their host. Our objective is to follow strict clinical validations so that everyone can benefit from the result of these millions of years of evolution.”