Slack, Cathy, Alic, Nazif, Foley, Andrea, Cabecinha, Melissa, Hoddinott, Matthew P. and Partridge, Linda (2015). The Ras-Erk-ETS-signaling pathway is a drug target for longevity. Cell, 162 (1), pp. 72-83.
Abstract
Summary 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
Publication DOI: | https://doi.org/10.1016/j.cell.2015.06.023 |
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Divisions: | College of Health & Life Sciences College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research |
Additional Information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Uncontrolled Keywords: | General Biochemistry,Genetics and Molecular Biology,General Medicine |
Publication ISSN: | 1097-4172 |
Last Modified: | 04 Dec 2024 08:10 |
Date Deposited: | 16 Mar 2017 12:15 |
Full Text Link: | |
Related URLs: |
http://www.scop ... tnerID=8YFLogxK
(Scopus URL) |
PURE Output Type: | Article |
Published Date: | 2015-07-02 |
Published Online Date: | 2015-06-25 |
Accepted Date: | 2015-05-21 |
Submitted Date: | 2014-10-30 |
Authors: |
Slack, Cathy
(
0000-0002-7949-4079)
Alic, Nazif Foley, Andrea Cabecinha, Melissa Hoddinott, Matthew P. Partridge, Linda |