Urolithin A: The Game-Changing Nutrient for Healthy Aging

When a team of scientists from EPFL, the Swiss Federal Institute of Technology in Lausanne, set out to thoroughly study the health benefits of pomegranates, they discovered something truly remarkable – the power of a postbiotic nutrient, Urolithin A (UA) to promote cellular health and longevity.

For the past 15 years, Urolithin A has been one of the most well-researched longevity molecules. Over 300 studies, 11 of which are clinical trials, show impressive benefits in UA’s ability to target some of the key biological hallmarks of aging.

These same scientists and doctors developed the first and only clinically tested Urolithin A formulation (more on that below!)

 

What is Urolithin A

Urolithin A is a postbiotic compound, meaning that we rely on our gut microbiome to create it. It is synthesized from polyphenols called ellagitannins, commonly found in pomegranates, berries, and some nuts.

UA promotes health in a unique way – by triggering an essential cellular recycling process called mitophagy. By rejuvenating the energy generators inside the cells (the mitochondria), it provides a host of positive downstream effects.

 

Urolithin A targets mitophagy

The key to understanding the ability of Urolithin A to optimize health is by understating its mechanism of action – mitophagy.

As we know, healthy mitochondria are vital to providing a constant supply of life-supporting energy in the form of ATP.  The decline in mitochondrial function over time has been identified as a hallmark of aging and has been implicated in a number of age-related chronic conditions, including declining skeletal muscle health, metabolic diseases, neurodegenerative disease and declining immune function.^1,2

Due to the critical nature of mitochondrial health, our bodies have developed a mitochondrial quality control method called mitophagy. This is the process by which old, damaged mitochondria are degraded and recycled into healthier ones that can produce energy more effectively.³

Interestingly, as we age, levels of mitophagy slow down, which is another biological hallmark of the aging process.¹

Urolithin A works by upregulating this important process.

 

The science behind Urolithin A

Early trials with Urolithin A conducted in worms and rodents demonstrated dramatic increases in lifespan and muscle performance. These positive results acted as the springboard to move into clinical trials studying UA’s role in improving human health.⁴

As muscle decline is a key characteristic of aging and is closely tied to mitochondrial function, muscle health has been a primary target for investigating UA’s benefits.

To date, three randomized, double-blind, placebo-controlled demonstrated marked improvements in cellular energy production, muscle strength, and endurance for individuals taking a highly pure, clinically tested UA formulation.

 

Unique Urolithin A formulation induces mitochondrial gene expression similar to aerobic exercise

This RCT compared UA supplementation (500 and 1000 mg) with placebo in sedentary elderly individuals. After four weeks, the two supplementation groups showed significant improvements in mitochondrial gene expression. The observed mitochondrial gene activity after taking UA is similar to that normally seen in healthy, active adults.⁴

Heatmap represents the genes that are the most significantly changed by the treatment within the GO_MITOCHONDRION genset

Andreux et al. (2019). The mitophagy activator Urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism; 1:595-603

 

Urolithin A  reduced muscle fatigue and improved endurance in older adults

This RCT compared 1000 mg of UA to a placebo in healthy elderly individuals (65 and older). After two months, the treatment group experienced significant improvements in leg (17%) and hand (16%) endurance and significant reductions in the inflammatory marker C-reactive protein.⁵

Liu et al. (2020) Effect of Urolithin A Supplementation on Muscle Endurance

and Mitochondrial Health in Older Adults. A Randomized Clinical Trial. JAMA Network Open; 5(1).

 

Urolithin A statistically improved muscle strength and endurance in middle-aged adults

Middle-aged adults (ages 45-65 years) were supplemented with either 500 mg or 1000 mg of UA or a placebo for four months in this RCT. The researchers observed clinically meaningful improvements with supplementation in measures of aerobic endurance and physical performance, as well as a 12% increase in muscle strength. Improvements in CRP levels were also observed.⁶

Singh 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, 3, 100633.

What’s particularly exciting about the results of all three of these studies is that no diet or exercise intervention occurred as part of the study design. This can offer a great benefit to people who are either unable or unwilling to include physical activity as part of their health journey.

 

Sources of Urolithin A

Urolithin A is a postbiotic compound, meaning that we must rely on our gut microbiome to make it. The dietary precursors for UA are ellagitannins, a class of polyphenols found in pomegranates, and some berries and nuts.

Unfortunately, most people do not have the right microbiome balance to produce UA. A recent study demonstrated that only 40% of individuals could produce detectable amounts after drinking pomegranate juice. And even for those individuals who could produce UA, they could not do so in quantities that studies have shown to be effective doses.⁷

Mitopure, a highly pure, clinically tested UA formulation, provides six times more Urolithin A than diet alone can.

 

What’s next for Urolithin A

Topical application of UA supports cellular energy in skin cells, helping to combat both intrinsic (internal) and extrinsic (external) aging factors. Several clinical trials have demonstrated healthy, more youthful-looking skin after only 2 weeks of use.

 

Upcoming trials

Urolithin A’s benefits go far beyond muscle & skin health. And due to the solid evidence in both pre-clinical and clinical trials, the interest in studying Urolithin A is exploding.

World-renowned researchers across the globe are investigating the potential benefits of  Urolithin A in the following settings:

• Elite athletes
• Immune health
• Brain health
• Skin health
• Chronic inflammation and inflammaging
• Arthritis
• Metabolic disorders

There is still much to learn about Urolithin A and its impact on health and longevity, but what we know already shows promise for this unique molecule. To learn more about the unique, clinically tested Urolithin A formulation Mitopure, head on over to Timelinenutrition.com.

 

 

About Timeline

Timeline is a Swiss longevity brand created by the MDs and PhDs who have pioneered the research on Mitopure (Urolithin A) for over a decade. As scientists, we know that physical decline from aging can’t be stopped. However, through its groundbreaking science, Timeline is committed to developing products designed to help reduce the impact of time on health. For more information, please visit timelinenutrition.com.

 

References:

1. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. Published online January 3, 2023. doi:10.1016/j.cell.2022.11.001
2. Haas RH. Mitochondrial Dysfunction in Aging and Diseases of Aging. Biology. 2019;8(2):48. doi:10.3390/biology8020048
3. Killackey SA, Philpott DJ, Girardin SE. Mitophagy pathways in health and disease. J Cell Biol. 2020;219(11):e202004029. doi:10.1083/jcb.202004029
4. Ryu D, Mouchiroud L, Andreux PA, et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med. 2016;22(8):879-888. doi:10.1038/nm.4132
5. Liu S, D’Amico D, Shankland E, et al. Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2022;5(1):e2144279. doi:10.1001/jamanetworkopen.2021.44279
6. Singh A, D’Amico D, Andreux PA, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep Med. 2022;3(5). doi:10.1016/j.xcrm.2022.100633
7. Singh A, D’Amico D, Andreux PA, et al. Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population. Eur J Clin Nutr. 2022;76(2):297-308. doi:10.1038/s41430-021-00950-1