As we age, it is common to feel a decline in energy, increased fatigue, susceptibility to seasonal illnesses, and slower wound healing. These signs often reflect the aging of the immune system, with reduced immune cell activity and increased inflammation creating a hidden burden on health. Recent research from Florian R. Greten’s team at Goethe University Frankfurt, published in Nature Aging, reveals that daily supplementation with 1000 mg of Urolithin A (UA) for four weeks can shift key immune cells in middle-aged adults (45–70 years) toward a younger, more functional state. This discovery highlights the potential of dietary adjustments or supplementation to “recharge” the immune system and counteract age-related decline.
What is Urolithin A?
Urolithin A (UA) is not directly present in food but is produced by gut microbiota through the metabolism of ellagitannins. Foods such as pomegranates, strawberries, walnuts, and raspberries, which are rich in ellagitannins, can be converted by gut bacteria into UA.
Interestingly, not everyone can efficiently perform this conversion. Research shows that UA production decreases with age, and only about 40% of older adults naturally generate meaningful levels of UA.
This phenomenon tightly links gut health, dietary choices, and aging, explaining why the same dietary patterns can produce different anti-aging effects in different individuals.
Core Anti-Aging Mechanism
UA’s most notable feature is its ability to act as a “mitophagy inducer.” In simple terms, it helps cells remove aging or dysfunctional mitochondria while promoting the generation of new, healthy mitochondria.
As we age, mitophagy efficiency declines, leading to impaired cellular energy factories, which is a hallmark of aging.
The 2025 Nature Aging study elucidates this mechanism: UA activates mitophagy, promoting the expansion of T memory stem cells and providing the immune system with rejuvenated, non-exhausted T cells.
This direct intervention at the cellular energy center offers a novel strategy to combat age-related immune dysfunction.
UA induces metabolic reprogramming in human immune cells
Immune System Rejuvenation
In the recent clinical trial, researchers examined UA’s impact on the human immune system. Fifty healthy adults aged 45–70 participated in a randomized, double-blind, placebo-controlled study.
After four weeks, participants receiving UA showed favorable changes in immune cell composition. Their CD8+ T cells shifted toward a more “naïve” and less exhausted state, with significantly enhanced fatty acid oxidation capacity.
The study also reported increased numbers of NK cells and non-classical monocytes in the peripheral blood of the UA group. Moreover, T-cell-induced tumor necrosis factor secretion and monocyte phagocytosis of bacteria improved.
These changes suggest that the immune system gained stronger anti-infective and anti-tumor capabilities. While the numerical changes were moderate, statistical significance indicates meaningful short-term immune remodeling.
UA alters peripheral immune frequencies and mitochondrial remodeling
Multi-System Benefits
Beyond the immune system, UA also protects muscle health. A 2022 clinical trial published in Cell Reports Medicine demonstrated that UA supplementation significantly improved muscle endurance, increasing the number of muscle contractions to fatigue.
The skin, the body’s largest organ, can also benefit from UA. Studies show that UA protects skin fibroblasts from UVA-induced photoaging by activating the NRF2 pathway and mitophagy to resist photodamage.
In cardiovascular health, UA exhibits anti-inflammatory properties and helps maintain endothelial function, potentially preventing atherosclerosis. Additional research suggests that UA can improve age-related circadian dysfunction, enhancing the amplitude of clock gene oscillations.
Collectively, these studies depict UA as a multi-target anti-aging compound capable of influencing multiple physiological systems.
How to Obtain and Supplement
The most direct way to obtain UA from food is to increase intake of pomegranates, strawberries, raspberries, and walnuts, which are rich in ellagitannins. However, due to individual differences in gut microbiota, UA production from the same foods may vary significantly among people.
For those unable to efficiently convert UA or seeking a more consistent dosage, supplementation may be an option.
References:
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Greten, F. R., et al. (2025). Urolithin A reshapes immune cell composition and metabolism in middle-aged adults. Nature Aging.
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Auwerx, J., et al. (2022). Urolithin A improves muscle strength and mitochondrial function in middle-aged adults. Cell Reports Medicine, 3(5), 100893.
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Zhao, W., et al. (2018). Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human SW620 colorectal cancer cells. Molecular Carcinogenesis, 57(2), 193-200.
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Focus Herb. (2025). Urolithin A protects the cardiovascular system.