The Ras-Erk-ETS-signaling pathway is a drug target for longevity

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
Divisions: Life & Health Sciences
Additional Information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords: Biochemistry, Genetics and Molecular Biology(all),Medicine(all)
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Related URLs: http://www.scopus.com/inward/record.url?scp=84934434966&partnerID=8YFLogxK (Scopus URL)
Published Date: 2015-07-02
Authors: Slack, Cathy ( 0000-0002-7949-4079)
Alic, Nazif
Foley, Andrea
Cabecinha, Melissa
Hoddinott, Matthew P.
Partridge, Linda

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