Urolithin A is one of a number of supplements under assessment for their ability to improve mitochondrial function in older adults. Mitochondria are the power plants of the cell, producing chemical energy store molecules vital to all cellular processes. Improved mitochondrial function should result in improved tissue function throughout the body, such as in skeletal muscle, a tissue with high energy requirements. You might recall the results published from a small human study earlier this year. Some measures of strength and endurance were improved, but as is the case for other, similar approaches to reducing age-related mitochondrial dysfunction, the gains are not as large as those that can be obtained via structured exercise programs. It is questionable as to whether significant time and funding should be devoted to these approaches.
Mitochondrial function declines with age, and evidence to date suggests that loss of efficacy in mitophagy is an important part of this aspect of degenerative aging. Mitophagy is a complex process of many stages in which damaged and worn mitochondria are identified, transported to a lysosome, and broken down. Defects in any part of this process, such as a reduced expression of critical proteins due to age-related changes in epigenetic regulation, will reduce overall efficiency of mitophagy. When mitophagy falters, dysfunctional mitochondria accumulate to the detriment of the cell. Urolithin A is thought to produce its benefits to mitochondrial function by restoring greater efficiency in mitophagy, though exactly how this is achieved is up for debate.
A new study shows that daily intake of Urolithin A significantly improved muscle strength by 12% after four months. This works by supporting the cells' ability to renew their power plants, the mitochondria, during the aging process. Muscles have a high demand for energy and there are a very large number of mitochondria in muscle cells.
Two measures of skeletal muscle strength were improved in the supplemented groups compared to the placebo group. Muscle strength in the hamstring skeletal muscle was significantly increased in both 500mg (+12%) and 1,000mg groups (+9.8%). Muscle strength during knee flexion was also significantly improved at both 500mg (+10.6%) and 1,000mg doses (+10.5%). The blood tests and biopsies showed a significant improvement in biomarkers of healthy mitochondrial function and reduced inflammation.
Targeting mitophagy to activate the recycling of faulty mitochondria during aging is a strategy to mitigate muscle decline. We present results from a randomized, placebo-controlled trial in middle-aged adults where we administer a postbiotic compound Urolithin A, a known mitophagy activator, at two doses for 4 months (NCT03464500). The data show significant improvements in muscle strength (∼12%) with intake of Urolithin A. We observe clinically meaningful improvements with Urolithin A on aerobic endurance (peak oxygen oxygen consumption [VO2]) and physical performance (6 min walk test) but do not notice a significant improvement on peak power output (primary endpoint).
Levels of plasma acylcarnitines and C-reactive proteins are significantly lower with Urolithin A, indicating higher mitochondrial efficiency and reduced inflammation. We also examine expression of proteins linked to mitophagy and mitochondrial metabolism in skeletal muscle and find a significant increase with Urolithin A administration.