Urolithin A may counteract age-related immune decline and inflammaging

Pomegranate
Urolithin A is a compound generated by gut microflora from ellagitannins found in food like pomegranate. (Getty Images/Boris Vasilenko)

Daily supplementation with urolithin A may help maintain immune function with age and protect against inflammaging, says data from a new randomized, double-blind, placebo-controlled trial.

Four weeks of supplementation with Mitopure, the high purity urolithin A from life sciences company Timeline, was associated with higher numbers of naive CD8+ T cells (fresh, responsive immune cells that decline with age), compared to placebo.

In addition, participants in the urolithin A (UA) group displayed augmented mitochondrial biogenesis in these CD8+ cells, reported scientists from Goethe University Frankfurt, Amazentis (parent company of Timeline), GBG Forschungs GmbH, Aix Marseille University and the Buck Institute for Research on Aging.

“Our data provide strong evidence that altering mitochondrial dynamics via the orally available and well-tolerated mitophagy inducer UA elicits systemic immune remodeling and potentially reduces the immune aging phenotype,” they wrote in Nature Aging.

“We therefore provide an intervention-based approach to limiting immune aging that may have potential to benefit chronic conditions characterized by immune dysfunction.”

Urolithin A

Urolithin A is a compound generated by gut microflora from ellagitannins found in food such as pomegranate. The compounds are hydrolyzed in the stomach into ellagic acid, which is subsequently converted by the gut microflora into urolithin A. However, not everyone has the right microflora to be able to make the metabolite.

Life sciences company Timeline (Amazentis) has developed a method to deliver finely calibrated doses of urolithin A. Preliminary data published in Nature Medicine indicated that urolithin A may improve mitochondrial function by stimulating mitophagy, a process by which damaged mitochondria are recycled to permit a renewal with healthy mitochondria. These potent beneficial effects have been demonstrated in several different organisms, including in human clinical trials.

Most of the data to date has focused on the ingredient’s benefits for muscle health, with clinical trials in a range of population and age groups. Results of a randomized clinical trial with 88 healthy people published in Cell Reports Medicine (2022) showed that urolithin A supplementation boosted exercise endurance and physical performance.

The new MitoImmune study extends the ingredient’s list of benefits to include protecting against age-related immune decline.

Study details

Fifty middle-aged adults were randomly assigned to receive 1,000 mg per day of urolithin A or placebo for four weeks.

Results showed that Mitopure was associated with improvements in the number of naive CD8+ T cells and reductions in inflammatory markers, including IL-6, TNF and IL-1β.

Additional analysis also showed that mitochondrial biogenesis increased in these CD8+ cells, while numbers of NK (natural killer) cells increased. NK cells are a type of immune-related white blood cell.

“As we age, our immune system naturally becomes less effective,” said Professor Florian Greten, MD, principal investigator and Director of the Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus and Goethe University Frankfurt. “What’s remarkable here is that urolithin A shows the potential to rejuvenate immune function by improving mitochondrial health, a completely new approach with real implications for healthy aging and quality of life.”

Collaborator Dr. Eric Verdin, MD, president and CEO of the Buck Institute of Aging, added: “It’s rare to see a supplement show measurable effects on immune aging in such a short time. By targeting the foundational cellular changes in immune cells instead of a temporary seasonal boost with Vitamin C for example, urolithin A offers a unique way to help rejuvenate immune function, something that no other supplement has demonstrated at this level.”

Next steps

The company also announced the launch of its 25th clinical trial, which will examine the effects of urolithin A on brain health. The Impact of a Novel Brain Longevity Supplement Containing the Postbiotic Urolithin A (Mitopure) on Cognitive Function and Related Health Outcomes (CLARITY) study is aiming to enroll 650 participants and is estimated to be completed by March 2026.

“Timeline is building the most clinically researched longevity consumer company in the world,” said Chris Rinsch, PhD, co-founder and president of Timeline. “We’re pushing the boundaries of healthspan science to enable people to stay stronger, sharper and more resilient as they age.”


Source: Nature Aging, 2025. doi: 10.1038/s43587-025-00996-x. “Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial”. Authors: D. Denk, et al.