Gut-Derived Urolithin A Rejuvenates Aging T Cells — A Potential Path to a Longer Healthspan

Researchers report that urolithin A (UA), a metabolite produced when gut bacteria break down ellagitannins found in foods such as pomegranates, walnuts, almonds and certain berries, can reverse key features of immune aging by acting on mitochondria inside T cells. Early human supplementation studies cited by the authors show improved T-cell function, increased mitochondrial quality control and reduced markers of inflammation—changes that could help lower age-related susceptibility to infections and cancer.

Where UA comes from
Ellagitannins are polyphenols present in several fruits, nuts and seeds. Intestinal microbes convert ellagitannins into metabolites called urolithins, of which urolithin A is the most studied. Individual responses depend on a person’s microbiome: not everyone converts ellagitannins to UA at the same rate or in the same amount.

What the new study found

A team led by Dominic Denk, a physician and cancer immunologist affiliated with University Hospital Frankfurt and the Georg-Speyer-Haus Institute for Tumor Biology and Experimental Therapy, published results in the journal Nature Aging showing that UA restores mitochondrial health in T cells. In trials referenced by the authors, UA supplementation increased numbers of functional cytotoxic T lymphocytes (CTLs) and enhanced mitophagy—the process that removes damaged mitochondria—while lowering oxidative stress and inflammatory signaling.

"Immune aging describes the global remodeling of the immune system that is characterized by reduced thymic output," Denk and colleagues write. "These changes cumulate in a chronic low-grade inflammatory state termed inflammaging that is characterized by increased concentrations of pro-inflammatory mediators favoring the development of heart disease and cancer."

Mechanism and significance

As we age, the thymus produces fewer new T cells and the balance of T-cell types shifts: memory T cells become more common while cytotoxic T cells—important for killing infected or malignant cells—decline. UA appears to prompt mitochondrial remodeling in CTLs, encouraging production of fresh, functional mitochondria and enhancing mitophagy to clear damaged ones. Restoring mitochondrial quality helps revive CTL energy and signaling capacity, which supports improved immune surveillance.

Because immunosenescence contributes to higher rates of infection and cancer in older adults, interventions that restore T-cell function could extend healthspan—the period of life spent free from chronic disease—and improve responses to infections and immunotherapies. However, the authors emphasize that further mechanistic studies are needed to understand how enhanced mitophagy affects responses to different challenges and other immune cell types.

Practical takeaways

• Eating ellagitannin-rich foods (pomegranate, certain berries, walnuts, almonds) may support gut-derived UA production in some people, but levels vary based on individual microbiomes.
• Early human studies of UA supplementation show promising immune effects, but larger clinical trials are required to confirm benefits, optimal dosing and long-term safety.
• UA is not a proven cure for cancer or aging; it is a promising candidate for therapies aimed at improving immune mitochondrial health and reducing inflammaging.

In sum, urolithin A—generated by gut microbes from compounds in common foods—has emerged as a biologically plausible way to rejuvenate aspects of the aging immune system. The discovery strengthens interest in microbiome-dependent metabolites as targets for therapies that could protect older adults from infection and age-related diseases, while cautioning that more research is needed before broad clinical use.