A meta-analysis of caloric restriction gene expression profiles to infer common signatures and regulatory mechanisms
Caloric restriction, a reduction in calorie intake without malnutrition, retards age-related degeneration and extends lifespan in several organisms. CR induces multiple changes, yet its underlying mechanisms remain poorly understood. In this work, we first performed a meta-analysis of microarray CR...
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| Published in | Molecular bioSystems Vol. 8; no. 4; pp. 1339 - 1349 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
01.04.2012
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Caloric restriction, a reduction in calorie intake without malnutrition, retards age-related degeneration and extends lifespan in several organisms. CR induces multiple changes, yet its underlying mechanisms remain poorly understood. In this work, we first performed a meta-analysis of microarray CR studies in mammals and identified genes and processes robustly altered due to CR. Our results reveal a complex array of CR-induced changes and we re-identified several genes and processes previously associated with CR, such as growth hormone signalling, lipid metabolism and immune response. Moreover, our results highlight novel associations with CR, such as retinol metabolism and copper ion detoxification, as well as hint of a strong effect of CR on circadian rhythms that in turn may contribute to metabolic changes. Analyses of our signatures by integrating co-expression data, information on genetic mutants, and transcription factor binding site analysis revealed candidate regulators of transcriptional modules in CR. Our results hint at a transcriptional module involved in sterol metabolism regulated by Srebf1. A putative regulatory role of Ppara was also identified. Overall, our conserved molecular signatures of CR provide a comprehensive picture of CR-induced changes and help understand its regulatory mechanisms. |
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| AbstractList | Caloric restriction, a reduction in calorie intake without malnutrition, retards age-related degeneration and extends lifespan in several organisms. CR induces multiple changes, yet its underlying mechanisms remain poorly understood. In this work, we first performed a meta-analysis of microarray CR studies in mammals and identified genes and processes robustly altered due to CR. Our results reveal a complex array of CR-induced changes and we re-identified several genes and processes previously associated with CR, such as growth hormone signalling, lipid metabolism and immune response. Moreover, our results highlight novel associations with CR, such as retinol metabolism and copper ion detoxification, as well as hint of a strong effect of CR on circadian rhythms that in turn may contribute to metabolic changes. Analyses of our signatures by integrating co-expression data, information on genetic mutants, and transcription factor binding site analysis revealed candidate regulators of transcriptional modules in CR. Our results hint at a transcriptional module involved in sterol metabolism regulated by Srebf1. A putative regulatory role of Ppara was also identified. Overall, our conserved molecular signatures of CR provide a comprehensive picture of CR-induced changes and help understand its regulatory mechanisms. |
| Author | Clarke, Susan A Wuttke, Daniel de Magalhães, João Pedro van Dam, Sipko Plank, Michael |
| Author_xml | – sequence: 1 givenname: Michael surname: Plank fullname: Plank, Michael organization: Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK – sequence: 2 givenname: Daniel surname: Wuttke fullname: Wuttke, Daniel – sequence: 3 givenname: Sipko surname: van Dam fullname: van Dam, Sipko – sequence: 4 givenname: Susan A surname: Clarke fullname: Clarke, Susan A – sequence: 5 givenname: João Pedro surname: de Magalhães fullname: de Magalhães, João Pedro |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22327899$$D View this record in MEDLINE/PubMed |
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| Snippet | Caloric restriction, a reduction in calorie intake without malnutrition, retards age-related degeneration and extends lifespan in several organisms. CR induces... |
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| SubjectTerms | Animals Caloric Restriction - methods Databases, Genetic Gene Expression Profiling - methods Gene Expression Regulation Lipid Metabolism - genetics Mammals Oligonucleotide Array Sequence Analysis - methods Signal Transduction Transcription Factors - genetics Transcription Factors - metabolism Transcription, Genetic |
| Title | A meta-analysis of caloric restriction gene expression profiles to infer common signatures and regulatory mechanisms |
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