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The gut microbiome controls gut health, communicating with colon cells, aiding the digestion of food, eradicating pathogens, and liaising with the brain. But thanks to scientific advancement, this wonderful ecosystem is more integral to the processes inside our bodies than we may have first thought.
First discovered more than four decades ago, urolithin A, a gut- microbiome derived compound, has become a focal point for understanding how aging can be slowed down. Despite knowing about it for over 40 years, it’s only recently that its impact on aging and disease progression has been investigated.
Here, we’ll briefly explore what urolithin A is before delving deep into its benefits on bone, muscle, and brain health.
Urolithin A is a natural compound produced by your gut bacteria. It is known as a postbioticbecause it is a product of prebiotic and probiotic digestion. Postbiotics have been linked to numerous health benefits. They do not contain any live microbes but may be superior to probiotics because they carry less risk of side effects and are just as effective as probiotics for health[i].
Urolithin A is a postbiotic produced after eating abundant dietary polyphenols called ellagitannins and ellagic acid, found in foods like pomegranate, nuts, and berries. The conversion of these polyphenols into urolithin A can only happen with the right bacteria in situ and declines with age. However, once urolithin A is absorbed it goes on to have huge benefits for your cells and mitochondria, the powerhouses of cells responsible for powering the biochemical reactions needed to produce energy.
One of the areas of human health where urolithin A has been identified as being useful is bone health, specifically the prevention of osteoarthritis and potentially osteoporosis.
The World Health Organisation (WHO) estimates that approximately 528 million people worldwide are living with osteoarthritis. Almost three-quarters (73%) are over 55 and 60% are women, suggesting it’s an age-related condition that prefers women, perhaps because of a decline in hormones during menopause[ii].
Osteoarthritis is driven by the destruction of joint tissue and the increased chondrocyte-mediated extracellular matrix degradation in the cartilage. Chondrocytes are the only cells present in cartilage and compared to healthy cartilage, osteoarthritic chondrocytes have a lower mitochondrial respiratory capacity.
That’s because joint cells are unable to generate new mitochondria and diseased joints accumulate dysfunctional mitochondria that they struggle to remove. Usually, the dysfunctional mitochondria would be eradicated through a process called mitophagy, but in osteoarthritis, and several other age-related conditions, it is impaired, aiding the progression of disease.
Mitophagy is the degradation of mitochondria. It is an autophagic mechanism, in other words, a cellular self-destruct button, that removes unnecessary or dysfunctional cellular components.
Mitophagy is thought to protect the body from diseases caused by mitochondrial dysfunction, such as osteoarthritis. However, when this process becomes impaired, it can leave room for age-related conditions to develop, so finding ways to suppress this deficit is key to improving outcomes.
A study by D’Amico and colleagues (2022) found that urolithin A increased mitophagy flux and activated a specific pathway involved in mitophagy called PINK1-Parkin, in both healthy and osteoarthritis cells. Therefore, suggesting that this activation improved mitochondrial respiration, leading to efficient cellular function.
That’s not all. The researchers also noticed that urolithin A reduced the pain associated with osteoarthritis, adding to its benefits for improving joint mobility. It was suggested that the pain benefits from urolithin A could be a direct result of the reduced structural damage in the joint tissues or the reduction in inflammation. However, more research is needed to draw a direct conclusion[iii].
Overall, the study shows promise for urolithin A to improve joint function and mobility through the activation of a distinct mitophagy pathway.
Did you know?3’-Siallylactose, a specific type of human milk oligosaccharide (HMO) has been identified as having a potential beneficial effect on the prevention and management of osteoarthritis. You can get yours in our SuperHMO Prebiotic Mix.
More recent research has also come to light about the effect of urolithin A on osteoporosis, a debilitating condition that results in depleted bone density, increasing the risk of fractures and falls, particularly in the elderly and postmenopausal women.
Zhou et al., (2024) studied the effect of urolithin A on osteoclast differentiation, a process in which osteoporosis increases. They also looked at the effect of urolithin A on bone loss in ovariectomy-induced osteoporotic mice. The results showed that urolithin A reduced the development of osteoclasts and bone loss in mice, suggesting urolithin A could be promising for the treatment and prevention of osteoporosis[iv].
Aside from its promise in bone health, urolithin A may also improve muscular health and performance, promoting the synthesis of muscle protein and growth, and slowing down the loss of muscle mass and strength[v].
Your muscles begin a downward decline from around the age of 40, and apart from exercise, there are no effective interventions to stop or reverse it. However, a study published in 2022 found that daily supplementation with urolithin A improved muscle strength by 12% in just 4 months.
The researchers found that hamstring and knee flexion muscle strength was improved with daily doses of 500 mg and 1000 mg of urolithin A. The 1000 mg group also showed improvements in power and aerobic endurance, so could walk further in a given amount of time. They also noted that there was a significant improvement in healthy mitochondrial biomarkers and lower inflammation[vi].
A small study published in 2022 also explored the effect of urolithin A supplementation on muscle performance and mitochondria in older adults. In the trial, 66 adults were given a 1000 mg daily supplement of urolithin A or a placebo for 4 months.
The researchers found that muscle endurance significantly improved in the urolithin A group and that inflammatory biomarkers such as C-reactive protein were reduced. Therefore, this suggests that urolithin A could be important in mitigating age-related muscle degeneration.
The potential physical benefits of urolithin A are clear, the gut-derived metabolite could support the health of our bones and muscles, particularly as we age, and they are most vulnerable to decline and damage.
There is growing evidence to suggest that urolithin A can effectively target the neurodegeneration associated with Alzheimer’s disease, holding promise for future interventions. Like other age-related conditions, impaired mitophagy is implicated in the development of Alzheimer’s disease but a study by Hou et al., (2024) demonstrated that urolithin A induced mitophagy in mouse models[vii]. Thus, could be beneficial for future Alzheimer’s disease interventions.
Parkinson’s disease prevalence has doubled in the last 25 years, affecting over 8.5 million people worldwide. The debilitating disease affects the brain causing issues with movement, balance, sleep, and mental health. There is no cure for Parkinson’s disease but there are medicines which can manage the symptoms[viii].
There have been several studies investigating the effect of urolithin A on the progression of Parkinson’s disease. In 2020, Kujawska and Co. examined the effect of pomegranate juice, rich in ellagitannins, in protecting mice with parkinsonism. They found that the pomegranate juice provided neuroprotection in the mice and showed that urolithin A was transported to the brain[ix].
Liu et al., (2022) found that urolithin A could regulate mitochondrial dysfunction in mice, suggesting its potential in managing Parkinson’s disease[x]. While Qiu et al., (2022) also found that urolithin A promotes mitophagy and reduces motor deficits and dopaminergic neurodegeneration in Parkinson-model mice.
Gong and colleagues (2022) investigated the potential impact of urolithin A on traumatic brain injury patients. For the first time, the researchers demonstrated that urolithin A, administered in 2.5 mg/kg doses, had neuroprotective effects in traumatic brain injuries. They found it does this by crossing the blood-brain barrier and reducing brain swelling, nerve cell death, and mitigating neurobehavioral deficits. It’s thought that Urolithin A’s ability to activate autophagy in the nerve cells and inhibit certain signalling pathways in the brain involved in neuroinflammation could be integral to its benefits.
Urolithin A is a gut-microbiome-derived compound produced when gut bacteria break down polyphenols. However, it has recently been hailed for its potential anti-aging benefits.
In this article, we briefly touched upon some of the recent discoveries and evidence that suggest urolithin A could have a positive impact on bone, muscle, and brain health. In many cases, these benefits are yielded through urolithin A’s ability to induce mitophagy, a process which clears out damaged and dysfunctional mitochondria, and one which has been implicated in the progression of several-age-associated conditions.
If nothing else, this research shows that urolithin A could hold great promise to help mitigate the effects of aging.
Written by: Leanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome.
[i] Vinderola G, Sanders ME, Salminen S. The Concept of Postbiotics. Foods. 2022 Apr 8;11(8):1077. doi: 10.3390/foods11081077. PMID: 35454664; PMCID: PMC9027423.
[ii] Osteoarthritis [Internet]. World Health Organization; [cited 2024 May 17]. Available from: https://www.who.int/news-room/fact-sheets/detail/osteoarthritis
[iii] D'Amico D, Olmer M, Fouassier AM, Valdés P, Andreux PA, Rinsch C, Lotz M. Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis. Aging Cell. 2022 Aug;21(8):e13662. doi: 10.1111/acel.13662. Epub 2022 Jul 1. PMID: 35778837; PMCID: PMC9381911.
[iv] Zhou W, Zhou W, Zhou Z, Bi Y, Zhou Z, Chen S, et al. Urolithin a attenuates osteoclast differentiation and compensates for ovariectomy-induced bone loss in mice by inhibiting PI3K/AKT/mtor signaling pathway. Phytomedicine Plus. 2024 Feb;4(1):100495. doi:10.1016/j.phyplu.2023.100495
[v] Zhao H, Song G, Zhu H, Qian H, Pan X, Song X, Xie Y, Liu C. Pharmacological Effects of Urolithin A and Its Role in Muscle Health and Performance: Current Knowledge and Prospects. Nutrients. 2023 Oct 19;15(20):4441. doi: 10.3390/nu15204441. PMID: 37892516; PMCID: PMC10609777.
[vi] Singh, A., et al. (2022) Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Reports Medicine. doi.org/10.1016/j.xcrm.2022.100633.
[vii] Hou Y, Chu X, Park J, Zhu Q, Hussain M, Li Z, et al. Urolithin a improves alzheimer’s disease cognition and restores mitophagy and lysosomal functions. Alzheimer’s & Dementia. 2024 May 16; doi:10.1002/alz.13847
[viii] Parkinson disease [Internet]. World Health Organization; [cited 2024 May 17]. Available from: https://www.who.int/news-room/fact-sheets/detail/parkinson-disease
[ix] Kujawska M, Jourdes M, Kurpik M, Szulc M, Szaefer H, Chmielarz P, et al. Neuroprotective effects of pomegranate juice against parkinson’s disease and presence of ellagitannins-derived metabolite—urolithin a—in the brain. International Journal of Molecular Sciences. 2019 Dec 27;21(1):202. doi:10.3390/ijms21010202
[x] Liu J, Jiang J, Qiu J, Wang L, Zhuo J, Wang B, et al. Urolithin a protects dopaminergic neurons in experimental models of parkinson’s disease by promoting mitochondrial biogenesis through the SIRT1/PGC-1α Signaling pathway. Food & Function. 2022;13(1):375–85. doi:10.1039/d1fo02534a
Aging is inevitable, but why do some people age better than others? The answer lies in a mix of genetic, environmental, and lifestyle factors. Another key player is the gut microbiome, which might hold the key to longevity and health. Using a review by Ghosh et al. (2022), we explore the role of the gut microbiome in healthy aging, chronic disease development, and strategies to help you age healthily.
