2014
DOI: 10.18632/aging.100665
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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 TO… Show more

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Cited by 48 publications
(66 citation statements)
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References 49 publications
(66 reference statements)
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“…An excess in amino acids might increase potentially toxic nitrogen waste products [10] or over-stimulate nutrient-sensing pathways that regulate lifespan (such as the TOR pathway [11][12][13]). The gut microbiota, which is important for ant nutrition [31] and sensitive to dietary macronutrients [32], might also play an important role in the physiological response to the diet.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…An excess in amino acids might increase potentially toxic nitrogen waste products [10] or over-stimulate nutrient-sensing pathways that regulate lifespan (such as the TOR pathway [11][12][13]). The gut microbiota, which is important for ant nutrition [31] and sensitive to dietary macronutrients [32], might also play an important role in the physiological response to the diet.…”
Section: Discussionmentioning
confidence: 99%
“…One hypothesis relates to protein digestion, which is energetically costly [8,9] and produces potentially toxic nitrogen waste products [10]. Another possibility is that absorbed amino acids stimulate signalling pathways that regulate lifespan, such as the canonical target of rapamycin (TOR) pathway [11][12][13]. A trade-off between longevity and reproduction complicates attempts to understand the effect of high-protein diets on lifespan; while decreasing longevity, high-protein diets improve the reproductive output of individuals [5,7,14,15].…”
Section: Introductionmentioning
confidence: 99%
“…43 The life extending effect of CR can be explained by inhibition of mTOR. [44][45][46][47][48][49] Fasting only minimally downregulated p-S6 in old mice, compared with young animals. 42 As we showed here, fasting levels of p-S6 were higher in old mice compared with middle-aged animals.…”
Section: Implications For Health-and Life-extensionmentioning
confidence: 92%
“…Similarly, Lee and colleagues found that under conditions where methionine reduction extends lifespan of wildtype flies, restriction of methionine no longer extends lifespan in InR DN mutants or in flies that overexpress the TOR antagonist tuberous sclerosis complex 2 (TSC2) [16]. Moreover, a recent study by Emran and colleagues has reported that TOR signaling, but apparently not IIS, is required for the effects of EAA on fecundity and lifespan [40]. These findings are also interesting given the observation that methionine-deficient mice exhibit lowered levels of serum IGF-1 and insulin [13].…”
Section: Amino Acids Affect Lifespan and Reproduction Via Nutrient Sementioning
confidence: 99%