A longer and healthier life with TOR down-regulation: genetics and drugs

被引：95

作者：

Bjedov, Ivana ^{[1
]}

Partridge, Linda ^{[1
,2
]}

机构：

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

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

来源：

BIOCHEMICAL SOCIETY TRANSACTIONS | 2011年 / 39卷

基金：

英国惠康基金;

关键词：

aging; autophagy; metabolism; stress; target of rapamycin (TOR); translation; DIET-INDUCED OBESITY; MTOR COMPLEX 1; SPAN EXTENSION; TRANSLATIONAL CONTROL; SIGNALING PATHWAY; GROWTH-FACTORS; C-ELEGANS; MECHANISMS; DROSOPHILA; AUTOPHAGY;

D O I：

10.1042/BST0390460

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genetic down-regulation of a major nutrient-sensing pathway, TOR (target of rapamycin) signalling, can improve health and extend lifespan in evolutionarily distant organisms such as yeast and mammals. Recently, it has been demonstrated that treatment with a pharmacological inhibitor of the TOR pathway, rapamycin, can replicate those findings and improve aging in a variety of model organisms. The proposed underlying anti-aging mechanisms are down-regulated translation, increased autophagy, altered metabolism and increased stress resistance.

引用

页码：460 / 465

页数：6

共 50 条

[1] The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C-elegans [J].

Apfeld, J ;

O'Connor, G ;

McDonagh, T ;

DiStefano, PS ;

Curtis, R .

GENES & DEVELOPMENT, 2004, 18 (24) :3004-3009

[2] Genetic links between diet and lifespan: shared mechanisms from yeast to humans [J].

Bishop, Nicholas A. ;

Guarente, Leonard .

NATURE REVIEWS GENETICS, 2007, 8 (11) :835-844

[3] Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster [J].

Bjedov, Ivana ;

Toivonen, Janne M. ;

Kerr, Fiona ;

Slack, Cathy ;

Jacobson, Jake ;

Foley, Andrea ;

Partridge, Linda .

CELL METABOLISM, 2010, 11 (01) :35-46

[4] Stressin' Sestrins take an aging fight [J].

Budanou, Andrei V. ;

Lee, Jun Hee ;

Karin, Michael .

EMBO MOLECULAR MEDICINE, 2010, 2 (10) :388-400

[5] mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells [J].

Chen, Chong ;

Liu, Yu ;

Liu, Yang ;

Zheng, Pan .

SCIENCE SIGNALING, 2009, 2 (98) :ra75

[6] Translational control of the innate immune response through IRF-7 [J].

Colina, Rodney ;

Costa-Mattioli, Mauro ;

Dowling, Ryan J. O. ;

Jaramillo, Maritza ;

Tai, Lee-Hwa ;

Breitbach, Caroline J. ;

Martineau, Yvan ;

Larsson, Ola ;

Rong, Liwei ;

Svitkin, Yuri V. ;

Makrigiannis, Andrew P. ;

Bell, John C. ;

Sonenberg, Nahum .

NATURE, 2008, 452 (7185) :323-U2

[7] Translational responses to growth factors and stress [J].

Cully, Megan ;

Downward, Julian .

BIOCHEMICAL SOCIETY TRANSACTIONS, 2009, 37 :284-288

[8] TOR complex 2: a signaling pathway of its own [J].

Cybulski, Nadine ;

Hall, Michael N. .

TRENDS IN BIOCHEMICAL SCIENCES, 2009, 34 (12) :620-627

[9] Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity [J].

De Martinis, M ;

Franceschi, C ;

Monti, D ;

Ginaldi, L .

FEBS LETTERS, 2005, 579 (10) :2035-2039

[10] Growth stimulation leads to cellular senescence when the cell cycle is blocked [J].

Demidenko, Zoya N. ;

Blagosklonny, Mikhail V. .

CELL CYCLE, 2008, 7 (21) :3355-3361

← 1 2 3 4 5 →