Tissue-specific transcriptome profiling of Drosophila reveals roles for GATA transcription factors in longevity by dietary restriction

Adam J. Dobson, Xiaoli He, Eric Blanc, Ekin Bolukbasi, Yodit Feseha, Mingyao Yang, Matthew D.W. Piper

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Abstract

Dietary restriction (DR) extends animal lifespan, but imposes fitness costs. This phenomenon depends on dietary essential amino acids (EAAs) and TOR signalling, which exert systemic effects. However, the roles of specific tissues and cell-autonomous transcriptional regulators in diverse aspects of the DR phenotype are unknown. Manipulating relevant transcription factors (TFs) specifically in lifespan-limiting tissues may separate the lifespan benefits of DR from the early-life fitness costs. Here, we systematically analyse transcription across organs of Drosophila subjected to DR or low TOR and predict regulatory TFs. We predict and validate roles for the evolutionarily conserved GATA family of TFs, and identify conservation of this signal in mice. Importantly, restricting knockdown of the GATA TF srp to specific fly tissues recapitulated the benefits but not the costs of DR. Together, our data indicate that the GATA TFs mediate effects of dietary amino acids on lifespan, and that by manipulating them in specific tissues it is possible to reap the fitness benefits of EAAs, decoupled from a cost to longevity. 

Original languageEnglish
Article number5
Number of pages8
Journalnpj Aging and Mechanisms of Disease
Volume4
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Keywords

  • Drosophila
  • ageing
  • transcription
  • GATA
  • fecundity
  • lifespan
  • diet
  • amino acids

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