Can Urolithin A supplementation reverse the effects of aging on muscles? Results from a randomized clinical study

Just as other bodily functions, the aging process influences muscle functionality. This influence manifests in the reduced capacity to perform physical activities and decreased muscle endurance. This decline in function is driven by reduced mitochondrial efficiency in utilizing adenosine triphosphate (ATP) to produce energy, leading to decreased muscle performance.

Cells usually eliminate aged and dysfunctional mitochondria by a selective autophagy process called mitophagy. With age, the cell’s capacity to eliminate the said mitochondria declines. This leads to the increased number of mitochondria with compromised functional capacity and quality. Restoration of the functional capacity of mitophagy has been explored as a potential pathway to improve mitochondrial function and limit the effects of the aging process. One of the natural compounds that have been found to influence mitophagy is Urolithin A (UA). UA is a natural food metabolite produced by the gut microbiome when metabolizing ellagitannins - natural compounds present in fruits like strawberries, pomegranates, and nuts.

To explore the potential of long-term supplementation of UA on mitochondrial function and muscle performance in older adults, Liu et al. initiated a randomized clinical study that extended for 4 months and assessed the efficacy of UA in comparison to placebo. To assess the efficacy, the researchers used a 6-minute walk distance as a primary endpoint to determine the efficacy of UA. Results of the study revealed that UA supplementation improved the mean 6-minute walk distance by about 15% (60.8 meters increase) from baseline compared to nearly 10% (42.5 meters increase) with placebo. Although the numbers were numerically in favor of UA, the results were not  statistically significant; however, both results were above the clinically relevant improvement cutoff of 30 meters. The secondary endpoint revealed a statistically significant increase in resistance to fatigue in the group supplemented with UA compared to placebo. The latter endpoint was measured using a custom-built exercise apparatus that calculated the number of contractions until fatigue. Biomarker analysis revealed that UA supplementation reduced levels of acylcarnitines, ceramides, and C-reactive protein. The highlighted biomarkers are implicated in mitochondrial health and inflammation. The authors concluded that UA supplementation was effective and that long-term supplementation may counteract the age-associated decline in function.

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