Creatine improves health and survival of mice

被引:73
作者
Bender, A.
Beckers, J.
Schneider, I.
Hoelter, S. M.
Haack, T.
Ruthsatz, T.
Vogt-Weisenhorn, D. M.
Becker, L.
Genius, J.
Rujescu, D.
Irmler, M.
Mijalski, T.
Mader, M.
Quintanilla-Martinez, L.
Fuchs, H.
Gailus-Durner, V.
de Angelis, M. Hrabe
Wurst, W.
Schmid, J.
Klopstock, T.
机构
[1] Univ Munich, Dept Neurol, Klinikum Grosshadern, D-81377 Munich, Germany
[2] GSF Natl Rs Ctr Environm & Hlth, German Mouse Clin, D-85764 Neuherberg, Germany
[3] GSF Natl Rs Ctr Environm & Hlth, Inst Expt Genet, D-85764 Neuherberg, Germany
[4] GSF Natl Rs Ctr Environm & Hlth, Inst Dev Genet, D-85764 Neuherberg, Germany
[5] GSF Natl Rs Ctr Environm & Hlth, Dept Comparat Med, D-85764 Neuherberg, Germany
[6] Univ Munich, Dept Psychiat, D-80336 Munich, Germany
[7] GSF Natl Res Centerfor Environm & Hlth GmbH, Inst Stem Cell Res, D-85764 Neuherberg, Germany
[8] GSF Natl Res Centerfor Environm & Hlth GmbH, Inst Pathol, D-85764 Neuherberg, Germany
关键词
creatine; aging; oxidative stress; mitochondria; lipofuscin; life span;
D O I
10.1016/j.neurobiolaging.2007.03.001
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
The supplementation of creatine (Cr) has a marked neuroprotective effect in mouse models of neurodegenerative diseases. This has been assigned to the known bioenergetic, anti-apoptotic, anti-excitotoxic, and anti-oxidant properties of Cr. As aging and neurodegeneration share pathophysiological pathways, we investigated the effect of oral Cr supplementation on aging in 162 aged C57B1/6J mice. Outcome variables included "healthy" life span, neurobehavioral phenotyping, as well as morphology, biochemistry, and expression profiling from brain. The median healthy life span of Cr-fed mice was 9% higher than in control mice, and they performed significantly better in neurobehavioral tests. In brains of Cr-treated mice, there was a trend towards a reduction of reactive oxygen species and significantly lower accumulation of the "aging pigment" lipofuscin. Expression profiling showed an upregulation of genes implicated in neuronal growth, neuroprotection, and learning. These data show that Cr improves health and longevity in mice. Cr may be a promising food supplement to promote healthy human aging. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:1404 / 1411
页数:8
相关论文
共 41 条
[1]   Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease [J].
Andreassen, OA ;
Dedeoglu, A ;
Ferrante, RJ ;
Jenkins, BG ;
Ferrante, KL ;
Thomas, M ;
Friedlich, A ;
Browne, SE ;
Schilling, G ;
Borchelt, DR ;
Hersch, SM ;
Ross, CA ;
Beal, MF .
NEUROBIOLOGY OF DISEASE, 2001, 8 (03) :479-491
[2]   Mitochondria take center stage in aging and neurodegeneration [J].
Beal, MF .
ANNALS OF NEUROLOGY, 2005, 58 (04) :495-505
[3]   High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease [J].
Bender, A ;
Krishnan, KJ ;
Morris, CM ;
Taylor, GA ;
Reeve, AK ;
Perry, RH ;
Jaros, E ;
Hersheson, JS ;
Betts, J ;
Klopstock, T ;
Taylor, RW ;
Turnbull, DM .
NATURE GENETICS, 2006, 38 (05) :515-517
[4]  
Bender A, 2005, J NEUROL, V252, P36, DOI 10.1007/s00415-005-0595-4
[5]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[6]  
Bertaina-Anglade V., 2006, Journal of Pharmacological and Toxicological Methods, V54, P99, DOI 10.1016/j.vascn.2006.04.001
[7]   A comparison of normalization methods for high density oligonucleotide array data based on variance and bias [J].
Bolstad, BM ;
Irizarry, RA ;
Åstrand, M ;
Speed, TP .
BIOINFORMATICS, 2003, 19 (02) :185-193
[8]  
BURGER JM, 2004, SCI AGING KNOWLEDGE, pPE30, DOI DOI 10.1126/SAGEKE.2004.28.PE30
[9]   Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice [J].
Duan, WZ ;
Guo, ZH ;
Mattson, MP .
JOURNAL OF NEUROCHEMISTRY, 2001, 76 (02) :619-626
[10]   Age-associated changes in protein oxidation and proteasome activities in rat brain: Modulation by antioxidants [J].
El Mohsen, MMA ;
Iravani, MM ;
Spencer, JPE ;
Rose, S ;
Fahim, AT ;
Motawi, TMK ;
Ismail, NAF ;
Jenner, P .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 336 (02) :386-391