Ras inhibition by trametinib treatment in Drosophila attenuates gut pathology in females and extends lifespan in both sexes

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][1]). 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][2]; [Selman et al. 2009][3]). 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][4]). 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][5]). 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. [1]: #ref-13 [2]: #ref-5 [3]: #ref-18 [4]: #ref-19 [5]: #ref-14