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

Dobson, A. J. , He, X., Blanc, E., Bolukbasi, E., Feseha, Y., Yang, M. and Piper, M. D.W. (2018) Tissue-specific transcriptome profiling of Drosophila reveals roles for GATA transcription factors in longevity by dietary restriction. npj Aging and Mechanisms of Disease, 4, 5. (doi: 10.1038/s41514-018-0024-4) (PMID:29675265) (PMCID:PMC5904217)

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.

• Item Type: Articles
• Additional Information: This study was funded by grants to MP from the Biotechnology and Biological Sciences Research Council (BBI011544/1), the Royal Society (UF100158 and RG110303) and the Australian Research Council (FT150100237).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dobson, Dr Adam
• Authors: Dobson, A. J., He, X., Blanc, E., Bolukbasi, E., Feseha, Y., Yang, M., and Piper, M. D.W.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: npj Aging and Mechanisms of Disease
• Publisher: Nature Publishing Group
• ISSN: 2056-3973
• ISSN (Online): 2056-3973
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in npj Aging and Mechanisms of Disease 4: 5
• Publisher Policy: Reproduced under a Creative Commons License