A natural substance derived from pomegranates can reverse key aspects of immune aging, scientists at the Georg-Speyer-Haus and University Hospital Frankfurt have successfully demonstrated. In a phase I clinical trial published in Nature Aging, the team led by Prof. Florian Greten and Dr. Dominic Denk showed that Urolithin A safely rejuvenates the immune systems of middle-aged adults, paving the way for new applications in infectious disease, aging, and cancer therapy.
As we age, our immune system begins to decline. This process, known as immune aging, leaves us more vulnerable to infections, less responsive to vaccines, and at greater risk for diseases like cancer. A key feature of this decline is the loss of “naïve” T cells – i.e. adaptable immune cells ready to fight new threats. The new work provides a promising strategy to counter this. The randomized, double-blind, placebo-controlled trial involved 50 healthy, middle-aged adults who received a daily dose of Urolithin A or a placebo for four weeks. The substance works by triggering “mitophagy,” a biological pathway that recycles and renews mitochondria, the “powerhouses” within cells. Participants who received Urolithin A showed a significant increase in their naive T cells, effectively replenishing their pool of “young” immune cells. The treatment also enhanced other key immune populations, improving their ability to clear bacteria and better preparing them to respond to new challenges.
The researchers built on their previous work, where they showed that Urolithin A could reprogram T cells and improve immune response against colorectal cancer in preclinical models.
“Three years ago, we discovered that Urolithin A could powerfully expand a special population of long-lived, anti-tumor T cells in our laboratory models,” explains Dr. med. Dominic Denk, MHBA, Principal Investigator of the study and physician-scientist at the Department of Medicine I, University Medicine Frankfurt. “Our goal was always to translate our findings from the lab into the clinic. This study is that critical first step and shows that Urolithin A can safely enhance immune function in humans. We are particularly excited about its potential in cancer treatment.”
“This successful clinical translation is a testament to our strategy at the Frankfurt Cancer Institute, to combine our findings with clinical expertise to accelerate the development of novel therapies that can truly make a difference,” says Prof. Dr. Florian Greten, Director of the Georg-Speyer-Haus and spokesperson for the LOEWE Center Frankfurt Cancer Institute. “A robust immune system has broad implications. By rejuvenating immune cells, we could make life-saving cancer treatments effective for more patients. We have already initiated a follow-up study in patients undergoing immunotherapy and are very eager to see whether our results will also have a positive effect here as well.”
