Bauer, J.H., Chang, C., Morris, S.N.S., Hozier, S., Andersen, S., Waitzman, J.S., Helfand, S.L. (2007). Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling.  Proc. Natl. Acad. Sci. U.S.A. 104(33): 13355--13360.

FBrf0201223

Research paper

In Drosophila melanogaster, p53 (Dmp53) is an important mediator of longevity. Expression of dominant-negative (DN) forms of Dmp53 in adult neurons, but not in muscle or fat body cells, extends lifespan. The lifespan of calorie-restricted flies is not further extended by simultaneously expressing DN-Dmp53 in the nervous system, indicating that a decrease in Dmp53 activity may be a part of the CR lifespan-extending pathway in flies. In this report, we show that selective expression of DN-Dmp53 in only the 14 insulin-producing cells (IPCs) in the brain extends lifespan to the same extent as expression in all neurons and this lifespan extension is not additive with CR. DN-Dmp53-dependent lifespan extension is accompanied by reduction of Drosophila insulin-like peptide 2 (dILP2) mRNA levels and reduced insulin signaling (IIS) in the fat body, which suggests that Dmp53 may affect lifespan by modulating insulin signaling in the fly.

PMC1948898 (PMC) (EuropePMC)