Urolithin A: Secret Weapon to Delay Aging and Revitalize Immunity

 

Urolithin A (UA), a postbiotic metabolite of ellagic acid and ellagitannins, has been widely recognized for its health benefits. Some common food sources of UA are pomegranates, strawberries, and walnuts. Studies have shown that UA can improve metabolic fitness in humans, and prolong the lifespan of worms by sustaining mitophagy and mitochondrial function. New research continues to unveil the potential health benefits of this natural anti-aging ingredient.

 

 

Recently, a research team led by the University of Lausanne published a new UA study in Nature Aging.[1] They found that UA can revert age-associated decline of hematopoietic, restoring blood reconstitution capability, and revitalizing immune systems. This study once again highlights the crucial role of mitochondrial homeostasis in the function of UA. Hematopoietic stem cells (HSCs) are essential to body health generating blood and immune cells throughout the entire life of an organism.[2] However, as we age, the number and functionality of HSCs gradually decline, leading to immune system aging and the onset of related diseases.[3] Previous studies have identified the link between the aging-related decline of HSCs and mitochondrial dysfunction.[4] Improving mitochondrial function in HSCs could restore their vitality. These connections prompted the team to question: Whether Urolithin A could take on this important task? In the study, HSCs of aged mice are extracted and treated with 20μM of UA for three days. After treatment, the cells are transplanted into recipient mice with depleted bone marrow. The results highlight that UA restored the blood reconstitution capability of old HSCs to the level of young cells. Additionally, consistent results were observed in mice fed with a UA-enriched diet (50 mg/kg/day) for 4 months.

 

Figure 1. UA in vitro treatment reverses age-associated defects in HSCs.

 

Notably, supplementing with UA also enhanced the proliferation of CD8+ T cells in aging mice and improved their response to viral infections. Further investigation into the mechanism revealed that UA promoted the circulation and renewal of mitochondria in old HSCs, restoring to "younger" and subsequently rejuvenating blood reconstitution capability and boosting immune function.

 

Figure 2. UA supplementation improves the CD8+ T cell response to viral infection in old mice, and induces mitochondrial recycling, and restores mitochondrial fitness.

 

Restoring UA levels in the body With aging, the elderly face increasing challenges of weakened immunity and increased susceptibility to infections. The health benefits of UA on restoring the immune system and overall cellular health making it vital for delaying aging and improving the quality of life for the elderly. However, solely relying on consuming food rich in ellagic acid and ellagitannins might not achieve the anti-aging effects of UA. Firstly, the dosage of UA used in studies is much higher than the amount found in fruits. This means that simply consuming fruits may not meet the effective dosage level. Secondly, other studies have shown that less than 40% of individuals can metabolize ellagic acid and ellagitannins into sufficient UA for use.[5] This implies that not everyone can obtain enough UA even from a diet that is rich in ellagic acid and ellagitannins. Additionally, compounds produced during the metabolism process, such as Urolithin B, Urolithin C, and Urolithin D, may increase the risk of cardiovascular diseases.[6]

 

Therefore, directly supplementing UA may be the optimal approach to achieve the anti-aging effects. UA supplements are now gaining popularity among consumers.

 

 

References:

1. Induction of mitochondrial recycling reverts age-associated decline of the hematopoietic and immune systems. DOI: 10.1038/s43587-023-00473-3

2. The aging of hematopoietic stem cells. DOI: 10.1038/nm0996-1011

3. Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. DOI: 10.1073/pnas.1116110108

4. Autophagy maintains the metabolism and function of young and old stem cells. DOI: 10.1038/nature21388

5. Impact of the Natural Compound Urolithin A on Health, Disease, and Aging. DOI: 10.1016/j.molmed.2021.04.009 6. The gut microbiota urolithin metabotypes revisited: The human metabolism of ellagic acid is mainly determined by aging. DOI: 10.1039/c8fo00956b

6. The gut microbiota urolithin metabotypes revisited: The human metabolism of ellagic acid is mainly determined by aging. DOI: 10.1039/c8fo00956b