Research Paper|Volume 6, Issue 5|pp 390—398

Target of rapamycin signalling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration

Sahar Emran¹, Mingyao Yang^1,², Xiaoli He¹, Jelle Zandveld³, Matthew D. W. Piper¹

¹Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom
²Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China
³Laboratory of Genetics, Wageningen University and Research Centre, 6708 PB, Wageningen, The Netherlands

Received: March 13, 2014Accepted: May 14, 2014Published: May 19, 2014

Copyright: © 2014 Emran et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Dietary restriction (DR), defined as a moderate reduction in food intake short of malnutrition, has been shown to extend healthy lifespan in a diverse range of organisms, from yeast to primates. Reduced signalling through the insulin/IGF-like (IIS) and Target of Rapamycin (TOR) signalling pathways also extend lifespan. In Drosophila melanogaster the lifespan benefits of DR can be reproduced by modulating only the essential amino acids in yeast based food. Here, we show that pharmacological downregulation of TOR signalling, but not reduced IIS, modulates the lifespan response to DR by amino acid alteration. Of the physiological responses flies exhibit upon DR, only increased body fat and decreased heat stress resistance phenotypes correlated with longevity via reduced TOR signalling. These data indicate that lowered dietary amino acids promote longevity via TOR, not by enhanced resistance to molecular damage, but through modified physiological conditions that favour fat accumulation.