Neuronal expression of p53 dominant-negative proteins in adult Drosophila melanogaster extends life span

Johannes H. Bauer, Peter C. Poon, Heather Glatt-Deeley, John M. Abrams, Stephen L. Helfand

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

Hyperactivation of p53 leads to a reduction in tumor formation and an unexpected shortening of life span in two different model systems [1, 2]. The decreased life span occurs with signs of accelerated aging, such as osteoporosis, reduction in body weight, atrophy of organs, decreased stress resistance, and depletion of hematopoietic stem cells. These observations suggest a role for p53 in the determination of life span and the speculation that decreasing p53 activity may result in positive effects on some aging phenotypes [3, 4]. In this report, we show that expression of dominant-negative versions of Drosophila melanogaster p53 in adult neurons extends life span and increases genotoxic stress resistance in the fly. Consistent with this, a naturally occurring allele with decreased p53 activity has been associated with extended survival in humans [5]. Expression of the dominant-negative Drosophila melanogaster p53 constructs does not further increase the extended life span of flies that are calorie restricted, suggesting that a decrease in p53 activity may mediate a component of the calorie-restriction life span-extending pathway in flies.

Original languageEnglish (US)
Pages (from-to)2063-2068
Number of pages6
JournalCurrent Biology
Volume15
Issue number22
DOIs
StatePublished - Nov 22 2005

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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