Aging will damage hematopoietic and immune functions, making the elderly susceptible to infectious diseases or tumors.
If the phenotype of aging hematopoietic stem cells can be reversed and restored to a “younger state,” it is expected to enhance their hematopoietic ability. It can improve the body’s immunity and prevent the occurrence of diseases.
Urolithin A Can Reverse The Aging Phenotype Of Hematopoietic Stem Cells
In August 2023, a research team composed of researchers from the University of Lausanne and Ecole Polytechnique Fédérale de Lausanne, led by Nicola Vannini, published an important research result in the famous journal “Nature Aging” .
They found that supplementing urolithin A through food can reverse the aging phenotype of aging hematopoietic stem cells and restore their hematopoietic function. In turn, it improves the immunity of aging mice against viral infection.
It should be noted that ellagic acid and ellagitannins contained in pomegranates, nuts, and some berries will produce urolithin A after metabolizing intestinal microorganisms.
Existing research has found that aging damage to the function of hematopoietic stem cells is related to mitochondria. In addition, as long as the function of mitochondria of hematopoietic stem cells can be improved, the function of hematopoietic stem cells can be restored.
Coincidentally, in the past few years, researchers at the Ecole Polytechnique Fédérale de Lausanne have found in a large number of studies that urolithin A can extend the lifespan of model animals or enhance the muscle function of model animals by improving mitochondrial function [2-4].
It prompted Vannini’s team to wonder whether urolithin A powder could reverse the aging phenotype of hematopoietic stem cells. Rejuvenate aging hematopoietic stem cells, thereby improving the immune system’s ability.
They first extracted senescent hematopoietic stem cells from aging mice (over 18 months old) and treated them with urolithin A at a concentration of 20 μM for 3 days. Then, they transplanted into myeloablative recipient mice. Judging from the research results, urolithin A treatment can restore the hematopoietic function of aging hematopoietic stem cells to the level of young mice aged 8-12 weeks.
In addition, studies on primary and secondary lymphoid tissues and a 20-week follow-up analysis further confirmed that brief urolithin A exposure can allow aging hematopoietic stem cells to regain long-lasting hematopoietic function.
Although the above in vitro experimental results have initially confirmed the effect of urolithin A. However, the clinical application of in vitro treatment is very difficult. Therefore, Vannini’s team conducted another study on oral supplementation of urolithin A.
They prepared a food rich in urolithin A for aging mice to ensure their daily intake was controlled at a level of 50mg/kg. After feeding at this level for 4 months, the blood cell composition of the mice in the urolithin A and the control groups was measured every month.
Test results showed that foods rich in urolithin A reversed the aging-related characteristics of the hematopoietic system. Subsequent transplantation experiments showed that dietary supplementation of urolithin A enhanced the function of hematopoietic stem and progenitor cells. And restored the number of common lymphoid progenitor cells in aging mice. What is particularly worth mentioning is that after supplementing urolithin A, the hematopoietic reconstruction ability of aging hematopoietic stem cells is equivalent to that of young mice. And restored lymphocyte production.
Does Urolithin A Powder Improve Immunity?
So, can the restoration of hematopoiesis improve the immunity of aging mice?
The results of viral infection experiments showed that the proliferation and effector capacity of aging CD8-positive T cells in mice supplemented with urolithin A were enhanced. Such mice are also better able to control the virus. Moreover, urolithin A-driven improvement in immune function in aging mice is due to its direct regulation of the functions of hematopoietic stem cells and T cells.
Is The Efficacy Of Urolithin A Powder Related To Mitochondria?
At the end of the study, Vannini’s team explored whether the mechanism by which urolithin A restores hematopoiesis and improves immunity is related to mitochondria.
Judging from the experimental results, urolithin A indeed promotes mitochondrial autophagy and regeneration. Simply put, urolithin A promotes mitochondrial recycling in aging hematopoietic stem cells. By removing old ones and regenerating new ones, the function of mitochondria is ensured, thereby improving the vitality of hematopoietic stem cells and restoring them to their “younger state.”
Can Eating Pomegranates Achieve The Researched Effects Of Urolithin A?
The answer is probably no.
First, the dose of urolithin A used in the study was relatively high (50mg/kg). You will definitely not be able to achieve this by eating pomegranates.
Secondly, although pomegranate contains the precursors of urolithin A (ellagic acid and ellagitannins), there is also a big variable of intestinal bacteria in the human body. The reason is that ellagic acid and the like can not only be metabolized by intestinal bacteria into urolithin A but also into urolithin B, urolithin C, urolithin D, and isourolithin A . The latter may not only be of no benefit but may increase the risk of cardiovascular disease .
Overall, the research by Vannini’s team shows that supplementing urolithin A powder improves immunity by improving the health of mitochondria and restoring the vitality of aging hematopoietic stem cells.
Vannini believes that their discovery has at least two practical implications.
First, urolithin A supplementation may significantly impact older adults because it strengthens their hematopoietic and immune systems, thereby reducing the risk of hematopoietic failure, enhancing immune surveillance, and improving their response to vaccination.
Second, patients undergoing chemotherapy may also benefit from urolithin A supplementation because chemotherapy can induce aging characteristics of the patient’s immune system, which may increase their susceptibility to pathogens and reduce their response to vaccination.
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- Girotra M, Chiang YH, Charmoy M, et al. Induction of mitochondrial recycling reverts age-associated decline of the hematopoietic and immune systems. Nat Aging. 2023;3(9):1057-1066. doi:10.1038/s43587-023-00473-3
- Ryu D, Mouchiroud L, Andreux PA, et al. Urolithin A induces mitophagy, prolongs lifespan in C. elegans, and increases muscle function in rodents. Nat Med. 2016;22(8):879-888. doi:10.1038/nm.4132
- Andreux PA, Blanco-Bose W, Ryu D, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab. 2019;1(6):595-603. doi:10.1038/s42255-019-0073-4
- Luan P, D’Amico D, Andreux PA, et al. Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy. Sci Transl Med. 2021;13(588):eabb0319. doi:10.1126/scitranslmed.abb0319
- Tomás-Barberán FA, González-Sarrías A, García-Villalba R, et al. Urolithins, the rescue of “old” metabolites to understand a “new” concept: Metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status. Mol Nutr Food Res. 2017;61(1). doi:10.1002/mnfr.201500901
- Selma MV, González-Sarrías A, Salas-Salvadó J, et al. The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: Comparison between norm weight, overweight-obesity, and metabolic syndrome. Clin Nutr. 2018;37(3):897-905. doi:10.1016/j.clnu.2017.03.012