Authors: Bauer JH; Chang C; Morris SN; Hozier S; Andersen S; Waitzman JS; Helfand SL
Abstract: 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.
Keywords: Animals; Base Sequence; Brain/*metabolism; DNA Primers; Drosophila Proteins/*genetics; Drosophila melanogaster; Energy Intake; *Genes, Dominant; Insulin/*metabolism; Life Expectancy; Signal Transduction/*genetics; Tumor Suppressor Protein p53/*genetics
Journal: Proceedings of the National Academy of Sciences of the United States of America Volume: 104 Issue: 33 Pages: 13355-60 Date: Aug. 10, 2007 PMID: 17686972 |
Bauer JH, Chang C, Morris SN, Hozier S, Andersen S, Waitzman JS, Helfand SL (2007) Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling. Proceedings of the National Academy of Sciences of the United States of America 104: 13355-60.
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