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bioRxiv · 10.1101/356295

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

Regan, J. C.·Lu, Y.-X.·Bolukbasi, E.·Khericha, M.·Partridge, L.
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Abstract

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.

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Regan, J. C., Lu, Y.-X., Bolukbasi, E., Khericha, M., Partridge, L.. 2018-06-26. Ras inhibition by trametinib treatment in Drosophila attenuates gut pathology in females and extends lifespan in both sexes. https://doi.org/10.1101/356295

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