Ursolic acid ameliorates aging-metabolic phenotype through promoting of skeletal muscle rejuvenation

Ursolic acid (UA) is a lipophilic compound, which highly found in apple peels. UA has some certain features, of the most important is its anabolic effects on skeletal muscles, which in turn plays a prominent role in the aging process, encouraged us to evaluate skeletal muscle rejuvenation. This study seeks to address the two following questions: primarily, we wonder to know if UA increases anti-aging biomarkers (SIRT1 and PGC-1α) in the isolated satellite cells, to pave the way for satellite cells proliferation. The results revealed that UA elevated the expression of SIRT1 (∼35 folds) and PGC-1α (∼175 folds) genes. The other question that needs to be asked, however, is to understand whether it is possible to generalize the in vitro findings to in vivo. For this, a study was designed to investigate the effects of UA on the cellular energy status in the animal models (C57BL/6 mice). We found that UA decreased cellular energy charges such as ATP (∼3 times) and ADP (∼18 times). With respect to the role of UA in energy expenditure and as an anti-aging biomarker, one might wonder to elucidate skeletal muscle rejuvenation as well as satellite cells proliferation and neomyogenesis. The results illustrated that UA boosted neomyogenesis through enhancing the number of satellite cells. In addition, rejuvenation effects of UA on the skeletal muscle promptly encouraged us to reexamine the performance of skeletal muscles. The results indicated that UA through increasing myoglobin expression (∼2 folds) accompanied with transforming of glycolytic to fast oxidative status chiefly and slow-twitch muscle fibers. To the best of our knowledge, it seems that UA might be considered as a potential candidate for treatment of pathological conditions associated with muscular atrophy and dysfunction, including skeletal muscle atrophy, amyotrophic lateral sclerosis (ALS), sarcopenia and metabolic diseases of the muscles.