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The Ras-Erk-ETS-Signaling Pathway Is a Drug Target for Longevity.

Slack, C; Alic, N; Foley, A; Cabecinha, M; Hoddinott, MP; Partridge, L; (2015) The Ras-Erk-ETS-Signaling Pathway Is a Drug Target for Longevity. Cell , 162 (1) pp. 72-83. 10.1016/j.cell.2015.06.023. Green open access

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Abstract

Identifying the molecular mechanisms that underlie aging and their pharmacological manipulation are key aims for improving lifelong human health. Here, we identify a critical role for Ras-Erk-ETS signaling in aging in Drosophila. We show that inhibition of Ras is sufficient for lifespan extension downstream of reduced insulin/IGF-1 (IIS) signaling. Moreover, direct reduction of Ras or Erk activity leads to increased lifespan. We identify the E-twenty six (ETS) transcriptional repressor, Anterior open (Aop), as central to lifespan extension caused by reduced IIS or Ras attenuation. Importantly, we demonstrate that adult-onset administration of the drug trametinib, a highly specific inhibitor of Ras-Erk-ETS signaling, can extend lifespan. This discovery of the Ras-Erk-ETS pathway as a pharmacological target for animal aging, together with the high degree of evolutionary conservation of the pathway, suggests that inhibition of Ras-Erk-ETS signaling may provide an effective target for anti-aging interventions in mammals. VIDEO ABSTRACT.

Type: Article
Title: The Ras-Erk-ETS-Signaling Pathway Is a Drug Target for Longevity.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2015.06.023
Publisher version: http://dx.doi.org/10.1016/j.cell.2015.06.023
Additional information: Copyright © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
URI: https://discovery.ucl.ac.uk/id/eprint/1469081
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