Cytochrome b5 reductase overexpression increases lifespan and oxidative stress resistance in fruit fly

Tuesday, October 09, 2012 — Poster Session I
1:00 p.m. – 3:00 p.m	Natcher Conference Center, Building 45	NIA	AGING-9

* FARE Award Winner

Authors

• Y Sun
• X Sun
• T Alberico
• A Wang
• R de Cabo
• S Zou

Abstract

Free radicals, mainly reactive oxygen species (ROS), have been proposed as one of the major causes of aging. Cytochrome b5 reductase (Cytb5R) has been shown to play an important role in the free radical defense system in both plasma membrane and mitochondria. Here we investigate the function of Cytb5R in modulating lifespan in the fruit fly, Drosophila melanogaster. Using the Gal4-UAS system, we overexpressed Cytb5R in flies and found that Cytb5R overexpression flies has a significant longer lifespan of female but not male fed a standard sugar-yeast-based diet (10% sugar, 10% yeast). Interestingly, overexpression of Cytb5R further increased mean lifespan of both male and female flies fed a calorie restriction diet (2.5% sugar, 2.5% yeast). Moreover, Cytb5R overexpression increased flies’ resistance to paraquat-induced oxidative stress. Our mechanistic studies indicated that Cytb5R overexpression increased the expression of stress response genes, including genes in Jun kinase (JNK) signaling, Nrf2 pathway and dSir2. In summary, our findings suggest that Cytb5R interacts with JNK, Nrf2 and/or sirtuin pathways to promote longevity. Thus, Cytb5R could be a novel target for prolongevity interventions.

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