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
[1]   Regulation of C-elegans longevity by specific gustatory and olfactory neurons [J].
Alcedo, J ;
Kenyon, C .
NEURON, 2004, 41 (01) :45-55
[2]   Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha [J].
Alessi, DR ;
James, SR ;
Downes, CP ;
Holmes, AB ;
Gaffney, PRJ ;
Reese, CB ;
Cohen, P .
CURRENT BIOLOGY, 1997, 7 (04) :261-269
[3]   Regulation of lifespan by sensory perception in Caenorhabditis elegans [J].
Apfeld, J ;
Kenyon, C .
NATURE, 1999, 402 (6763) :804-809
[4]   FoxOs in tumor suppression and stem cell maintenance [J].
Arden, Karen C. .
CELL, 2007, 128 (02) :235-237
[5]   A search for the origins of animals and fungi: Comparing and combining molecular data [J].
Baldauf, SL .
AMERICAN NATURALIST, 1999, 154 :S178-S188
[6]   No extension of lifespan by ablation of germ line in Drosophila [J].
Barnes, AI ;
Boone, JM ;
Jacobson, J ;
Partridge, L ;
Chapman, T .
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2006, 273 (1589) :939-947
[7]   C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span [J].
Berdichevsky, Ala ;
Viswanathan, Mohan ;
Horvitz, H. Robert ;
Guarente, Leonard .
CELL, 2006, 125 (06) :1165-1177
[8]   Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1 [J].
Biggs, WH ;
Meisenhelder, J ;
Hunter, T ;
Cavenee, WK ;
Arden, KC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (13) :7421-7426
[9]   Extended longevity in mice lacking the insulin receptor in adipose tissue [J].
Blüher, M ;
Kahn, BB ;
Kahn, CR .
SCIENCE, 2003, 299 (5606) :572-574
[10]   Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction [J].
Bonkowski, Michael S. ;
Rocha, Juliana S. ;
Masternak, Michal M. ;
Al Regaiey, Khalid A. ;
Bartke, Andrzej .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (20) :7901-7905