Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: Comparison of the long-term effects of calorie restriction without malnutrition on global gene expression profiles of rat and human skeletal muscle [Rat]      
dateReleased:
08-01-2013
description:
With the population of older and overweight individuals on the rise in the Western world, there is an ever greater need to slow the aging processes and reduce the burden of age-associated chronic disease that would significantly improve the quality of human life and reduce economic costs. Caloric restriction (CR), is the most robust and reproducible intervention known to delay aging and to improve healthspan and lifespan across species (1); however, whether this intervention can extend lifespan in humans is still unknown. Here we report that rats and humans exhibit similar responses to long-term CR at both the physiological and molecular levels. CR induced broad phenotypic similarities in both species such as reduced body weight, reduced fat mass and increased the ratio of muscle to fat. Likewise, CR evoked similar species-independent responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with improved health and survival: IGF-1/insulin signaling, mitochondrial biogenesis and inflammation. To our knowledge, these are the first results to demonstrate that long-term CR induces a similar transcriptional profile in two very divergent species, suggesting that such similarities may also translate to lifespan-extending effects in humans as is known to occur in rodents. These findings provide insight into the shared molecular mechanisms elicited by CR and highlight promising pathways for therapeutic targets to combat age-related diseases and promote longevity in humans. Male Fisher 344 rats (n=54) were randomly assigned to two groups at 2 months of age. One group was kept ad libitum (AL) fed throughout their lifespan while the calorie restriction (CR) group was progressively brought down to a 40% CR. All animals were fed a NIH-31 standard chow (Harlan Teklad, Indianapolis, IN, USA). Rats were singly housed in an environmentally controlled vivarium with unlimited access to water and a controlled photoperiod (12 hr. light;12 hr. dark). Body weights and food intake were recorded biweekly. All rats were maintained between 68-72°F according to animal protocols and NIH guidelines. Total RNA was extracted from the vastus lateralis skeletal muscle using Trizol Reagent (Invitrogen, Carlsbad, CA) following the manufacturer’s instructions, n=5 from each group. Total RNA samples were biotin labeled and hybridized to RatRef-12 v1 Gene Expression beadchips (Illumina, San Diego, CA) following Illumina protocols. Arrays were washed and scanned using an Illumina BeadArray 500GX reader. Microarray florescent signals were extracted using the Illumina GenomeStudio Gene Expression software(v1.6.0) and any spots at or below the background were filtered using an Illumina detection p-value of 0.02 and above. The natural log of all remaining scores were used to find the avg and std of each array and the z-score normalization was calculated . Correlation analysis, sample clustering analysis and principal component analysis include all of probes are performed to identify/exclude any possible outliners. The resulting dataset was next analyzed with DIANE 6.0, a spreadsheet based microarray analysis program. Gene set enrichment analysis use gene expression values or gene expression change values for all of the genes in the microarray. Parametric analysis of gene set enrichment (PAGE) was used [pubmed 20682848] for gene set analysis. Gene Sets include the MSIG database [Link], Gene Ontology Database [Link], GAD human disease and mouse phenotype gene sets [pubmed: 20092628] were used to explore functional level changes.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-38062
refinement:
raw
alternateIdentifiers:
38062
keywords:
functional genomics
dateModified:
08-12-2013
availability:
available
types:
gene expression
name:
Rattus norvegicus
ID:
A-GEOD-10239
name:
Illumina Rat Ref-12 v1
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-38062/E-GEOD-38062.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-38062/E-GEOD-38062.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38062
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

Feedback?

If you are having problems using our tools, or if you would just like to send us some feedback, please post your questions on GitHub.