Scientists at Germany’s Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, have unveiled promising findings regarding a natural compound known as urolithin A (UA). This metabolite, produced in the gut through the consumption of foods like pomegranates and walnuts, has demonstrated the ability to rejuvenate the immune system in middle-aged individuals, potentially offering protection against cell damage, inflammation, and chronic diseases, including cancer.
The research, published on March 15, 2024, in the journal Nature Aging, follows a significant breakthrough in 2022, when the research team first identified UA’s capacity to activate a biological pathway that rejuvenates mitochondria—the power generators of cells—in T cells.
Dr. Dominic Denk, a physician-scientist at University Medicine Frankfurt, expressed the goal of translating laboratory findings into clinical applications. “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,” he stated. “Our goal was always to translate our findings from the lab into the clinic.”
As people age, they undergo a process known as immunosenescence, which leads to a gradual decline in both the innate and adaptive immune systems. This deterioration increases inflammation and susceptibility to infections and age-related diseases. A notable aspect of this decline is the loss of naive T cells—crucial for fighting pathogens—while memory T cells increase, diminishing the body’s ability to respond effectively to new infections.
To investigate UA’s effects on immune health, the researchers conducted a randomized, double-blind, controlled trial involving 50 healthy adults aged between 45 and 70 years. Participants received either UA supplements or a placebo for 28 days, with immune-related health markers assessed before and after the treatment period.
The results indicated significant improvements in immune function among those taking UA. Specifically, there was an increase in the number of well-functioning CD8+ T cells, known for their role in combating pathogens. These cells exhibited higher levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a protein essential for mitochondrial biogenesis, which is the process by which cells create new mitochondria.
Additionally, participants who received UA supplements displayed reduced oxidative stress and changes in several inflammatory markers, highlighting UA’s ability to trigger mitophagy—a process that recycles and renews cellular energy sources. This led to a notable increase in young, naive T cells, enhancing the immune system’s capacity to eliminate harmful bacteria.
The effectiveness of UA is closely tied to the gut microbiota, with certain microbial groups believed to play a role in metabolizing ellagitannins from foods like pomegranates. The growing body of research surrounding UA has expanded its potential applications, with studies exploring its use in treating conditions such as depression, enhancing muscle endurance and strength, and even addressing obesity by promoting the conversion of white fat to brown fat.
“This study is that critical first step and shows that urolithin A can safely enhance immune function in humans,” said Dr. Denk. He added that while the focus has been on UA’s potential in cancer treatment, the benefits may extend well beyond oncology, particularly in alleviating cellular dysfunction associated with aging.
Dr. Florian Greten, Director of Georg-Speyer-Haus, emphasized the broader implications of a robust immune system. “By rejuvenating immune cells, we could make life-saving cancer treatments effective for more patients,” he remarked. The team has already initiated a follow-up study involving patients undergoing immunotherapy, hoping to see similarly positive results.
The implications of this research extend beyond individual health, pointing toward new avenues for enhancing immune function in aging populations. As the global population continues to age, understanding and harnessing the power of natural compounds like urolithin A may play a crucial role in improving health outcomes and quality of life.
