Reviewing the Development of Urolithin A as an Age-Slowing Intervention

Of the supplement compounds that have been shown to in some way improve mitochondrial function, urolithin A is probably the least well understood when it comes to how exactly it works. This is interesting, as a range of academic and industry groups are presently working on it or derivatives of it. A reasonable view of this class of approach to mitochondrial dysfunction in aging, which also includes MitoQ and vitamin B3 derivatives like nicotinamide riboside, is that the interventions likely produce much of their effect by improving the operation of the mitochondrial quality control processes of mitophagy. They may achieve this quite indirectly, as mitophagy is complex and appears strongly affected by changes in mitochondrial dynamics and function. Impaired mitophagy leading to damaged mitochondria and impaired mitochondrial function is a feature of aging. The primary objection to a focus on supplements to improve mitochondrial function is that, so far, exercise produces better results.

Urolithin A (UA) is a gut metabolite derived from ellagic acid. This systematic review assesses the potential geroprotective effect of UA in humans. In five studies including 250 healthy individuals, UA (10-1000 mg/day) for a duration ranging from 28 days to 4 months, showed a dose-dependent anti-inflammatory effect and upregulated some mitochondrial genes, markers of autophagy, and fatty acid oxidation. It did not affect mitochondrial maximal adenosine triphosphate production, biogenesis, dynamics, or gut microbiota composition. UA increased muscle strength and endurance, however, had no effect on anthropometrics, cardiovascular outcomes, and physical function.

There is very limited evidence on the effect of UA in human aging. UA showed some improvement in mitochondrial activity and autophagy. It decreased inflammatory markers and increased muscle strength and endurance. Taken together, current evidence does not support the beneficial effects of UA on physical function in healthy individuals. However, this conclusion should be considered in light of several limitations: small sample sizes, short intervention durations, and a wide participant age range (45-85 years), which includes both middle-aged and older individuals who may not be ideal candidates for geroprotection.

Link: https://doi.org/10.1016/j.arr.2024.102406

Comments

Have some UA arriving next week. Will be interested to determine if any effects are noticeable in comparison with the effect of my pomegranate supplementation which was…. moot.

Posted by: William at August 1st, 2024 6:06 AM

my subjective observation is that GHKCu, later combined with urolithin, improved my poor performance (due to damaged lungs) while 25 years of exercise couldn't.

Posted by: SilverSeeker at August 1st, 2024 11:14 AM

@William
A couple of years ago UA used to cost an arm and leg.

Posted by: Cuberat at August 1st, 2024 11:22 PM

@Cuberat

yes, it still seems a bit too dear for my wallet but Mitopure was having a sale so I thought I would try it out. It's now been a couple of weeks but I haven't been able to notice any specific changes in energy levels and can't test my mitophagy markers at home. That being said I have been on the road and not able to attend to my usual gym routine. I am now at home again and perhaps more will be revealed when I hit the gym this weekend.

Posted by: William at August 29th, 2024 7:28 AM
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