Forkhead transcription factors and ageing

被引:74
作者
Partridge, L. [1 ]
Bruening, J. C. [2 ]
机构
[1] Inst Healthy Aging, London WC1E 6BT, England
[2] Univ Cologne, Inst Genet, Dept Mouse Genet & Metab, D-5000 Cologne, Germany
基金
英国惠康基金;
关键词
forkhead transcription factor; FOXO; signaling; ageing; lifespan; ageing-related disease;
D O I
10.1038/onc.2008.28
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
Mutations in single genes and environmental interventions can extend healthy lifespan in laboratory model organisms. Some of the mechanisms involved show evolutionary conservation, opening the way to using simpler invertebrates to understand human ageing. Forkhead transcription factors have been found to play a key role in lifespan extension by alterations in the insulin/IGF pathway and by dietary restriction. Interventions that extend lifespan have also been found to delay or ameliorate the impact of ageing-related pathology and disease, including cancer. Understanding the mode of action of forkheads in this context will illuminate the mechanisms by which ageing acts as a risk factor for ageing-related disease, and could lead to the development of a broad-spectrum, preventative medicine for the diseases of ageing.
引用
收藏
页码:2351 / 2363
页数:13
相关论文
共 135 条
[21]   Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase [J].
Cheung, WL ;
Ajiro, K ;
Samejima, K ;
Kloc, M ;
Cheung, P ;
Mizzen, CA ;
Beeser, A ;
Etkin, LD ;
Chernoff, J ;
Earnshaw, WC ;
Allis, CD .
CELL, 2003, 113 (04) :507-517
[22]   Using FlyAtlas to identify better Drosophila melanogaster models of human disease [J].
Chintapalli, Venkateswara R. ;
Wang, Jing ;
Dow, Julian A. T. .
NATURE GENETICS, 2007, 39 (06) :715-720
[23]   Dietary restriction in long-lived dwarf flies [J].
Clancy, DJ ;
Gems, D ;
Hafen, E ;
Leevers, SJ ;
Partridge, L .
SCIENCE, 2002, 296 (5566) :319-319
[24]   Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein [J].
Clancy, DJ ;
Gems, D ;
Harshman, LG ;
Oldham, S ;
Stocker, H ;
Hafen, E ;
Leevers, SJ ;
Partridge, L .
SCIENCE, 2001, 292 (5514) :104-106
[25]   Opposing activities protect against age-onset proteotoxicity [J].
Cohen, Ehud ;
Bieschke, Jan ;
Perciavalle, Rhonda M. ;
Kelly, Jeffery W. ;
Dillin, Andrew .
SCIENCE, 2006, 313 (5793) :1604-1610
[26]  
DAVIS RJ, 1994, CANCER RES, V54, P2869
[27]   Timing requirements for insulin/IGF-1 signaling in C-elegans [J].
Dillin, A ;
Crawford, DK ;
Kenyon, C .
SCIENCE, 2002, 298 (5594) :830-834
[28]  
DORMAN JB, 1995, GENETICS, V141, P1399
[29]   WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION [J].
ELDEIRY, WS ;
TOKINO, T ;
VELCULESCU, VE ;
LEVY, DB ;
PARSONS, R ;
TRENT, JM ;
LIN, D ;
MERCER, WE ;
KINZLER, KW ;
VOGELSTEIN, B .
CELL, 1993, 75 (04) :817-825
[30]   FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK [J].
Essers, MAG ;
Weijzen, S ;
de Vries-Smits, AMM ;
Saarloos, I ;
de Ruiter, ND ;
Bos, JL ;
Burgering, BMT .
EMBO JOURNAL, 2004, 23 (24) :4802-4812