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

Sahar Emran1, Mingyao Yang1,2, Xiaoli He1, Jelle Zandveld3, and Matthew D. W. Piper1
1 Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom.
2 Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.
3 Laboratory of Genetics, Wageningen University and Research Centre, 6708 PB, Wageningen, The Netherlands.
Key words:
Drosophila melanogaster, rapamycin, target of rapamycin signalling, phenotyping, lifespan, stress response, essential amino acids
3/13/14; Accepted: 5/14/14; Published: 5/19/14


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. InDrosophila 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.