Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of brains from mice fed with or without creatine supplementation to study the molecular mechanism of creatine improving health and life span in mice

ABSTRACT: Here we show that oral creatine (Cr) supplementation leads to increased life span in mice. Treated mice showed improved neurobehavioral performance, decreased accumulation of the aging pigment lipofuscin and upregulation of anti-aging genes in brain. As Cr is virtually free of adverse effects, it may be a promising food supplement for healthy aging in man. Experiment Overall Design: 6 biological replicates for creatine-treated mice, 7 biological replicates for untreated mice.

ORGANISM(S): Mus musculus

SUBMITTER: Martin Irmler

PROVIDER: E-GEOD-5140 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Creatine improves health and survival of mice.

Bender A A Beckers J J Schneider I I Hölter S M SM Haack T T Ruthsatz T T Vogt-Weisenhorn D M DM Becker L L Genius J J Rujescu D D Irmler M M Mijalski T T Mader M M Quintanilla-Martinez L L Fuchs H H Gailus-Durner V V de Angelis M Hrabé MH Wurst W W Schmidt J J Klopstock T T

Neurobiology of aging 20070409 9

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, bioch ...[more]

PMID: 17416441

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Project description:Background: Calorie restriction (CR) is the only intervention known to extend lifespan in a wide range of organisms, including mammals. However, the mechanisms by which it regulates mammalian aging remain largely unknown and the involvement of the TOR and Sirtuin pathways (which regulate aging in lower organisms) remain controversial. Femaleness is a second phenotype generally associated with longevity but the relationship between sex-biased and CR-induced gene expression remains undetermined. Methodology/Principal Findings: We generated microarray gene expression data from livers of male mice fed high calorie or CR diets, and we find that CR significantly changes the expression of over 3,000 genes, many between 10- and 50-fold. We compare our data to the GenAge database of known aging-related genes and to prior microarray expression data of genes expressed differently between male and female mice. CR generally feminizes gene expression and many of the most significantly changed individual genes are involved in aging, hormone signaling, and p53-associated regulation of the cell cycle and apoptosis. Among the genes showing the largest and most statistically significant CR-induced expression differences are Ddit4, a key regulator of the TOR pathway, and Nnmt, a regulator of lifespan linked to the Sirtuin pathway. Using Western analyses, we confirmed post-translational inhibition of the TOR pathway. Conclusions: Our data show that CR induces widespread gene expression changes and acts through highly evolutionarily conserved pathways, from microorganisms to mammals, and that its life-extension effects might arise partly from a shift toward a gene expression profile more typical of the longer-lived female sex. Keywords: Two-class gene expression comparison. Calorie restriction (CR) versus HIGH CALORIE feeding. Design of the experiment is a two-class paired design in which the two classes are HIGH CALORIE and CALORIE RESTRICTION (CR) dietary regimens fed to mice, resulting in 15 HIGH CALORIE microarrays and 8 CR microarrays; 23 total microarrays. Four HIGH CALORIE and 2 CR microarrays were produced using pools of 3 RNA samples for each microarray (6 pools of 3, plus 17 individual samples = 35 individual mouse liver samples, 23 microarrays). Total liver RNA was labeled directly. Reference RNA: Stratagene Universal Mouse Reference RNA.

Dataset Information

Transcription profiling of brains from mice fed with or without creatine supplementation to study the molecular mechanism of creatine improving health and life span in mice

Publications

Creatine improves health and survival of mice.

Similar Datasets

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