title: Target of rapamycin signalling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration.
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. 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.
authors.affiliation: Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Sahar
authors.initials: S
authors.lastname: Emran
authors.forename: Mingyao
authors.initials: M
authors.lastname: Yang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: He
authors.forename: Jelle
authors.initials: J
authors.lastname: Zandveld
authors.forename: Matthew D W
authors.initials: MD
authors.lastname: Piper
mesh_terms: D000601:Amino Acids, Essential / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000601:Amino Acids, Essential; D029721:Drosophila Proteins; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases