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)

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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 > Institute of Molecular Cell and Systems Biology
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

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