Creatine improves health and survival in mice

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 C57Bl/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. © 2007 Elsevier Inc. All rights reserved.

[1]  V. Bertaina-Anglade,et al.  The object recognition task in rats and mice: a simple and rapid model in safety pharmacology to detect amnesic properties of a new chemical entity. , 2006, Journal of pharmacological and toxicological methods.

[2]  N. Nadon.  Of mice and monkeys: National Institute on Aging resources supporting the use of animal models in biogerontology research. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[3]  Robert W. Taylor,et al.  High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease , 2006, Nature Genetics.

[4]  A. Navarro,et al.  Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[5]  J. Spencer,et al.  Age-associated changes in protein oxidation and proteasome activities in rat brain: modulation by antioxidants. , 2005, Biochemical and biophysical research communications.

[6]  M. Beal,et al.  Mitochondria take center stage in aging and neurodegeneration , 2005, Annals of neurology.

[7]  M. Emond,et al.  Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria , 2005, Science.

[8]  Jean YH Yang,et al.  Bioconductor: open software development for computational biology and bioinformatics , 2004, Genome Biology.

[9]  D. Allison,et al.  The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice. , 2004, Free radical biology & medicine.

[10]  R. Thomson,et al.  A systematic review of cognitive decline in the general elderly population , 2003, International journal of geriatric psychiatry.

[11]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

[12]  J. Lawler,et al.  Direct antioxidant properties of creatine. , 2002, Biochemical and biophysical research communications.

[13]  O. Andreassen,et al.  Creatine Increases Survival and Delays Motor Symptoms in a Transgenic Animal Model of Huntington's Disease , 2001, Neurobiology of Disease.

[14]  P G Schultz,et al.  The effects of aging on gene expression in the hypothalamus and cortex of mice. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[15]  C. Li,et al.  Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Mattson,et al.  Brain‐derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice , 2001, Journal of neurochemistry.

[17]  M. Mattson,et al.  Dietary restriction protects hippocampal neurons against the death-promoting action of a presenilin-1 mutation , 1999, Brain Research.

[18]  M. Beal,et al.  Creatine and Cyclocreatine Attenuate MPTP Neurotoxicity , 1998, Experimental Neurology.

[19]  S. Melov,et al.  Multi-organ characterization of mitochondrial genomic rearrangements in ad libitum and caloric restricted mice show striking somatic mitochondrial DNA rearrangements with age. , 1997, Nucleic acids research.

[20]  M. Laakso,et al.  Prevalence of age-associated memory impairment in a randomly selected population from eastern Finland , 1995, Neurology.

[21]  Denham Harman,et al.  The Biologic Clock: The Mitochondria? , 1972, Journal of the American Geriatrics Society.

[22]  S. Irwin,et al.  Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse , 1968, Psychopharmacologia.

[23]  J. Manson,et al.  Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer The Women ’ s Health Study : A Randomized Controlled Trial , 2005 .

[24]  R. Reilmann,et al.  Creatine supplementation lowers brain glutamate levels in Huntington’s disease , 2005, Journal of Neurology.

[25]  Richard Weindruch,et al.  Caloric restriction and aging. , 1996, Scientific American.

[26]  S. Ferris,et al.  A visual recognition memory test for the assessment of cognitive function in aging and dementia. , 1987, Experimental aging research.