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.
journal_name
Celljournal_title
Cellauthors
Slack C,Alic N,Foley A,Cabecinha M,Hoddinott MP,Partridge Ldoi
10.1016/j.cell.2015.06.023subject
Has Abstractpub_date
2015-07-02 00:00:00pages
72-83issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(15)00707-2journal_volume
162pub_type
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