Deprenyl (Selegiline) inhibits monoamine oxidase B (MAO-B), an endogenous enzyme that breaks down dopamine. As a result, an excess of dopamine is present in patients taking this drug, which helps treat the symptoms of Parkingson’s disease. Interestingly, published studies indicate that deprenyl increases lifespan in rats, though the mechanism is unknown. In order to determine the mechanism by which deprenyl extends lifespan, our lab has turned to the tractable model organism C. elegans. Deprenyl has recently been shown to prevent dopamine metabolism in C. elegans, and our lab has demonstrated that 0.10 mM deprenyl has a wide range of effects on N2 animals. It delays development and the onset of reproduction, but does not inhibit reproduction or the number of viable offspring. Deprenyl has been shown to increase the median lifespan of N2 worms by 15% and maximum lifespan by 13%. In the lab, it has been seen that deprenyl does not inhibit pharyngeal pumping and reduces age-induced paralysis in the animals. Deprenyl also protects the worms against heat stress. To deduce the mechanism by which deprenyl has these effects, C. elegans deficient in dopamine (cat-2) and the lifespan-regulating transcription factor DAF-16 were treated with deprenyl, and their phenotypes were scored. Deprenyl slows the development of cat-2 worms, but does not consistently affect developmental rate of daf-16 worms. Deprenyl protects cat-2 worms against heat stress and requires DAF-16 for its protective effect, increases youthful movement in cat-2 worms and requires DAF-16 for its protective effect, and protects daf-16 mutants from oxidative stress, but did not protect cat-2 worms. Interestingly, at the effective doses, deprenyl did not induce nuclear localization of GFP-tagged DAF-16 (DAF-16::GFP).

Deducing the mechanism by which deprenyl increases lifespan in C. elegans

255th National Meeting (2018)

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