1. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents.
- Author
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Ryu D, Mouchiroud L, Andreux PA, Katsyuba E, Moullan N, Nicolet-Dit-Félix AA, Williams EG, Jha P, Lo Sasso G, Huzard D, Aebischer P, Sandi C, Rinsch C, and Auwerx J
- Subjects
- Animals, Caenorhabditis elegans, DNA, Mitochondrial drug effects, DNA, Mitochondrial metabolism, Fertility drug effects, Mice, Microscopy, Confocal, Mitochondria metabolism, Muscle, Skeletal metabolism, Myoblasts metabolism, Oxygen Consumption, Pharynx drug effects, RNA, Messenger metabolism, Rats, Real-Time Polymerase Chain Reaction, Coumarins pharmacology, Longevity drug effects, Mitochondria drug effects, Mitophagy drug effects, Muscle, Skeletal drug effects, Myoblasts drug effects, RNA, Messenger drug effects
- Abstract
The biological effects of urolithins remain poorly characterized, despite wide-spread human exposure via the dietary consumption of their metabolic precursors, the ellagitannins, which are found in the pomegranate fruit, as well as in nuts and berries. We identified urolithin A (UA) as a first-in-class natural compound that induces mitophagy both in vitro and in vivo following oral consumption. In C. elegans, UA prevented the accumulation of dysfunctional mitochondria with age and extended lifespan. Likewise, UA prolonged normal activity during aging in C. elegans, including mobility and pharyngeal pumping, while maintaining mitochondrial respiratory capacity. These effects translated to rodents, where UA improved exercise capacity in two different mouse models of age-related decline of muscle function, as well as in young rats. Our findings highlight the health benefits of urolithin A and its potential application in strategies to improve mitochondrial and muscle function.
- Published
- 2016
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