Urolithin A: Recycling Your Mitochondria for Longer Life
Your gut bacteria should make it from pomegranates — but most people's can't. Urolithin A triggers mitophagy, and clinical trials show real muscle benefits in older adults.
What if one of the most powerful anti-aging molecules came from pomegranates — but your gut bacteria couldn't produce it?
Your Mitochondria Are Dying (and That's the Problem)
Every cell in your body contains hundreds to thousands of mitochondria — the tiny powerhouses that convert food into energy. When you're young, your cells run a tight ship: damaged mitochondria get tagged, dismantled, and recycled through a process called mitophagy (literally "mitochondria eating").
Think of it like a city's waste management system. When a power plant breaks down, you demolish it and build a fresh one. Efficient. Clean. Functional.
But as you age, this recycling system slows down. Damaged mitochondria accumulate. They leak reactive oxygen species, trigger inflammation, and produce less energy. Your cells start running on broken generators — and you feel it as fatigue, muscle weakness, slower recovery, and cognitive decline.
This mitochondrial decline isn't just a symptom of aging. Many researchers now believe it's a driver of aging. Fix the mitochondria, and you might fix a significant piece of the aging puzzle.
Enter urolithin A.
What Is Urolithin A?
Urolithin A (UA) is a natural compound produced when your gut bacteria transform ellagitannins — polyphenols found in pomegranates, walnuts, raspberries, and strawberries. When you eat a pomegranate or a handful of walnuts, your intestinal microbiome breaks down the ellagitannins into ellagic acid, and then further converts that into urolithins.
Here's the catch: most people's gut bacteria can't do this efficiently. Studies show that the conversion depends on having specific bacterial species (Gordonibacter urolithinfaciens and Gordonibacter pamelaeae, among others), and the efficiency varies dramatically between individuals. Some people produce abundant urolithin A after eating pomegranates. Others produce almost none.
This means that no matter how many pomegranates you eat, your body might not be making the compound that actually delivers the benefits. It's like having all the ingredients for a recipe but missing the chef.
That's why researchers developed a way to supplement urolithin A directly — bypassing the gut bacteria lottery entirely.
The Science: From Worms to Humans
The Breakthrough Discovery (2016)
The story begins at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland. In 2016, a team led by Dongryeol Ryu and Johan Auwerx published a landmark paper in Nature Medicine showing that urolithin A activates mitophagy — the cellular recycling program for damaged mitochondria.
The results in C. elegans (a model organism widely used in aging research) were striking:
- UA extended lifespan by over 45%
- It prevented the accumulation of dysfunctional mitochondria with age
- It maintained mobility and pharyngeal pumping (measures of healthspan) during aging
- These effects translated to rodents: older mice given UA showed improved exercise capacity and muscle function
This was the first identification of a natural compound that could specifically activate mitophagy. Not just an antioxidant. Not just an anti-inflammatory. A targeted mitochondrial recycler.
First Human Clinical Trial (2019)
The same research group, now working with the Swiss biotech company Amazentis, conducted the first-in-human clinical trial of urolithin A. Published in Nature Metabolism in 2019, the trial enrolled healthy, sedentary elderly individuals and tested UA at multiple doses.
Key findings:
- UA was safe and well-tolerated at all doses tested (the primary outcome)
- It was bioavailable in plasma — meaning it actually reaches your bloodstream and tissues
- After 4 weeks of supplementation at 500 mg and 1,000 mg, participants showed significant changes in plasma acylcarnitines (biomarkers of mitochondrial fat metabolism)
- Skeletal muscle biopsies revealed upregulation of mitochondrial genes — molecular evidence that mitophagy was being activated in human tissue
This was a critical step: proving that what worked in worms and mice also produced measurable molecular changes in humans.
The ATLAS Trial: Muscle Strength and Performance (2022)
The most compelling human evidence came from the ATLAS trial, a randomized, double-blind, placebo-controlled study published in Cell Reports Medicine in 2022. Led by Anurag Singh and colleagues at Amazentis, it tested urolithin A (marketed as Mitopure) in middle-aged adults for 4 months.
The results:
| Measure | Result |
|---|---|
| 💪 Muscle strength (hand grip + leg) | ~12% improvement |
| 🏃 Aerobic endurance (VO₂ peak) | Clinically meaningful improvement |
| 🚶 Physical performance (6-min walk test) | Improved |
| 🔥 Plasma C-reactive protein | Significantly reduced (less inflammation) |
| ⚡ Plasma acylcarnitines | Reduced (better mitochondrial efficiency) |
| 🧬 Muscle mitophagy proteins | Significantly increased |
A 12% improvement in muscle strength in 4 months is remarkable for any intervention — especially one that doesn't involve exercise. To put that in context, age-related muscle loss (sarcopenia) typically proceeds at 1–2% per year after age 50. This supplement was effectively reversing several years of muscle decline.
The study also confirmed that UA was working through the expected mechanism: muscle biopsies showed increased expression of proteins directly linked to mitophagy and mitochondrial metabolism.
What Makes Urolithin A Special
Several things set urolithin A apart in the crowded supplement landscape:
1. It Has a Clear, Specific Mechanism
Unlike many supplements that claim vague "antioxidant" benefits, UA has a defined molecular target: mitophagy activation. Scientists can measure exactly what it does at the cellular level — it triggers the selective removal of damaged mitochondria and stimulates the production of new, healthy ones.
2. Multiple Human Clinical Trials
This is rare in the supplement world. Most supplements have zero human trials, or a single small study. Urolithin A has been tested across multiple randomized, controlled human trials — from safety and bioavailability studies to functional outcomes like muscle strength and endurance. The evidence base is unusually strong for a nutritional compound.
3. It Addresses a Root Cause of Aging
Mitochondrial dysfunction is considered one of the nine hallmarks of aging (as defined in the landmark López-Otín et al. 2013 paper). By targeting mitophagy, UA doesn't just treat a symptom — it addresses one of the fundamental biological processes that drives aging across multiple organ systems.
4. The Gut Microbiome Gap
The fact that most people can't efficiently produce UA from food makes direct supplementation particularly compelling. You're not just getting "more" of something — you're getting something your body likely wasn't producing at meaningful levels in the first place.
The Commercial Product: Mitopure by Timeline
The primary commercial form of urolithin A is Mitopure, produced by Amazentis (marketed under the brand Timeline). This is the same company that funded and conducted the clinical trials — which is worth noting for transparency.
Mitopure is:
- The proprietary, highly pure form of urolithin A used in the clinical studies
- Available as softgels, powder, and protein powder formats
- Dosed at 500 mg per serving (the clinically tested dose)
- Granted GRAS (Generally Recognized As Safe) status by the US FDA in 2018
The typical recommended dose is 500–1,000 mg daily, based on the clinical trial protocols. The 500 mg dose showed significant effects on molecular biomarkers, while 1,000 mg showed similar safety and potentially enhanced benefits.
Price reality: Mitopure is not cheap — expect roughly $50–70 per month depending on the format. This positions it as a premium supplement, though the clinical backing is stronger than most products in that price range.
Who Might Benefit Most
Based on the available evidence, urolithin A may be particularly relevant for:
- Adults over 40 experiencing early signs of age-related muscle decline
- Sedentary individuals who aren't getting the mitochondrial benefits of regular exercise
- Anyone concerned about mitochondrial health as part of a longevity strategy
- People who don't produce UA naturally from dietary sources (which is most people, though you can't easily test this outside a research setting)
Important Caveats
- The clinical trials have been relatively short-term (4 weeks to 4 months). Long-term effects over years are still unknown.
- Most studies have been funded by Amazentis, the manufacturer. While published in peer-reviewed journals, independent replication would strengthen the evidence.
- UA is not a replacement for exercise. Exercise remains the most powerful intervention for mitochondrial health. UA may complement it, but it's not a substitute.
- The optimal dose for long-term use is still being studied. Current evidence supports 500–1,000 mg daily.
- If you have a medical condition or take medications, consult your doctor before starting any new supplement.
The Bottom Line
Urolithin A is one of the most scientifically credible longevity supplements to emerge in recent years. It has a clearly defined mechanism (mitophagy activation), multiple human clinical trials showing real functional improvements, and addresses one of the fundamental hallmarks of aging.
The fact that most people can't efficiently produce it from food makes supplementation a logical strategy — though the relatively high cost and industry-funded research are fair considerations.
If you're building a longevity supplement stack and want something that targets mitochondrial health specifically, urolithin A belongs on your shortlist. Just don't expect it to replace the basics: sleep, exercise, nutrition, and stress management remain the foundation.
Sources
Ryu D, Mouchiroud L, Andreux PA, et al. "Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents." Nature Medicine. 2016;22(8):879-888. DOI: 10.1038/nm.4132. PMID: 27400265.
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." Nature Metabolism. 2019;1(6):595-603. DOI: 10.1038/s42255-019-0073-4. PMID: 32694802.
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 Reports Medicine. 2022;3(5):100633. DOI: 10.1016/j.xcrm.2022.100633. PMID: 35584623.
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 Network Open. 2022;5(1):e2144279. DOI: 10.1001/jamanetworkopen.2021.44279. PMID: 35050355.
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. "The Hallmarks of Aging." Cell. 2013;153(6):1194-1217. DOI: 10.1016/j.cell.2013.05.039. PMID: 23746838.