Drosophila foxo acts in males to cause sexual-dimorphism in tissue-specific p53 life span effects

Exp Gerontol. 2010 Feb;45(2):97-105. doi: 10.1016/j.exger.2009.10.009. Epub 2009 Oct 17.

Abstract

Sex-specific selective pressures are hypothesized to lead to sexually antagonistic gene functions that contribute to phenotypes such as aging and cancer. However, relatively little is known about the identity of such genes and possible mechanisms. Here we report that nervous system-specific over-expression of wild-type p53 in Drosophila caused decreased life span in males and increased life span in females. In contrast, tissue-general over-expression produced the opposite pattern: increased life span in males and decreased life span in females. In a foxo null background, p53 life span effects in males were reversed, becoming similar to the effects in females. In contrast, a Sir2 null background tended to reduce the magnitude of p53 effects. The data demonstrate that wild-type p53 over-expression can regulate life span independent of foxo, and suggest that foxo acts in males to produce sexually antagonistic life span effects of p53.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology*
  • Animals
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / physiology
  • Female
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Life Expectancy
  • Male
  • Mutation
  • Phosphorylation / physiology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sex Characteristics*
  • Sex Differentiation / genetics
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Drosophila Proteins
  • FOXO protein, Drosophila
  • Forkhead Transcription Factors
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-akt
  • Sirt2 protein, Drosophila
  • Sirtuins
  • Histone Deacetylases