PT  - JOURNAL ARTICLE
AU  - Regan, Jennifer C
AU  - Lu, Yu-Xuan
AU  - Bolukbasi, Ekin
AU  - Khericha, Mobina
AU  - Partridge, Linda
TI  - Ras inhibition by trametinib treatment in <em>Drosophila</em> attenuates gut pathology in females and extends lifespan in both sexes
AID  - 10.1101/356295
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 356295
4099  - http://biorxiv.org/content/early/2018/06/26/356295.short
4100  - http://biorxiv.org/content/early/2018/06/26/356295.full
AB  - Females of most species live longer than do males. Furthermore, lifespan-extending interventions in laboratory model organisms are often more effective in females (Regan and Partridge 2013). For instance, genetic and pharmacological suppression of activity of the insulin/insulin-like signalling - target of rapamycin (IIS-TOR) network generally extends female lifespan more than that of males in both Drosophila and mice (Clancy et al. 2001; Selman et al. 2009). We previously showed that attenuation of Ras-dependent IIS signalling by treatment with the FDA-approved MEK inhibitor, trametinib extends lifespan in females (Slack et al. 2015). Here, we demonstrate that trametinib treatment has beneficial effects on female-specific, age-related gut pathologies, similar to those obtained through dietary restriction (Regan et al. 2016). Importantly, we identify Ras inhibition as an effective lifespan-extending manipulation in males as well as females, pointing to parallel mechanisms of lifespan extension by trametinib in both sexes.