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The Ras-Erk-ETS-signaling pathway is a drug target for longevity
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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. doi:10.1016/j.cell.2015.06.023 ISSN 0092-8674.
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Official URL: http://doi.org/10.1016/j.cell.2015.06.023
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.
Item Type: | Journal Article | |||||||||||||||
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Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Ras proteins, Ras proteins -- Inhibitors, Protein kinases, Cellular signal transduction, Longevity, Aging, Cells -- Aging | |||||||||||||||
Journal or Publication Title: | Cell | |||||||||||||||
Publisher: | Cell Press | |||||||||||||||
ISSN: | 0092-8674 | |||||||||||||||
Official Date: | 5 July 2015 | |||||||||||||||
Dates: |
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Volume: | 162 | |||||||||||||||
Number: | 1 | |||||||||||||||
Page Range: | pp. 72-83 | |||||||||||||||
DOI: | 10.1016/j.cell.2015.06.023 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 18 May 2023 | |||||||||||||||
Date of first compliant Open Access: | 18 May 2023 | |||||||||||||||
RIOXX Funder/Project Grant: |
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