Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster

被引：793

作者：

Bjedov, Ivana ^{[1
]}

Toivonen, Janne M. ^{[1
]}

Kerr, Fiona ^{[1
]}

Slack, Cathy ^{[1
]}

Jacobson, Jake ^{[1
,2
]}

Foley, Andrea ^{[1
]}

Partridge, Linda ^{[1
,2
]}

机构：

[1] UCL, Dept Genet Evolut & Environm, Inst Healthy Ageing, London WC1E 6BT, England

[2] Max Planck Inst Biol Aging, D-50931 Cologne, Germany

来源：

CELL METABOLISM | 2010年 / 11卷 / 01期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

S6; KINASE; DIETARY RESTRICTION; AUTOPHAGY GENES; INSULIN-RESISTANCE; STRESS RESISTANCE; CELL-SURVIVAL; TOR; GROWTH; PROTEIN; YEAST;

D O I：

10.1016/j.cmet.2009.11.010

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The target of rapamycin (TOR) pathway is a major nutrient-sensing pathway that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. The central component of this pathway, TOR kinase, is the target of the inhibitory drug rapamycin, a highly specific and well-described drug approved for human use. We show here that feeding rapamycin to adult Drosophila produces the life span extension seen in some TOR mutants. Increase in life span by rapamycin was associated with increased resistance to both starvation and paraquat. Analysis of the underlying mechanisms revealed that rapamycin increased longevity specifically through the TORC1 branch of the TOR pathway, through alterations to both autophagy and translation. Rapamycin could increase life span of weak insulin/lgf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms.

引用

页码：35 / 46

页数：12

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