Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 33, Pages 13355-13360Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0706121104
Keywords
Drosophila melanogaster; lifespan extension; p53
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Funding
- NIA NIH HHS [AG25277, RF1 AG024353, AG16667, AG24353, R37 AG016667, R01 AG016667, R01 AG025277, R01 AG024353] Funding Source: Medline
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in Drosophila melanogaster, p53 (Dmp53) is an important mediator of longevity. Expression of dominant-negative (DIN) 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-extencling 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 pepticle 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.
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