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Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
Published on: November 27, 2019
Comparative analysis of microarray data identifies common responses to caloric restriction among mouse tissues
1Department of Pathology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48103, United States. wswindel@med.umich.edu
Abstract:
Caloric restriction has been extensively investigated as an intervention that both extends lifespan and delays age-related disease in mammals. In mice, much interest has centered on evaluating gene expression changes induced by caloric restriction (CR) in particular tissue types, but the overall systemic effect of CR among multiple tissues has been examined less extensively. This study presents a comparative analysis of microarray datasets that have collectively examined the effects of CR in 10 different tissue types (liver, heart, muscle, hypothalamus, hippocampus, white adipose tissue, colon, kidney, lung and cochlea). Using novel methods for comparative analysis of microarray data, detailed comparisons of the effects of CR among tissues are provided, and 28 genes for which expression response to CR is most shared among tissues are identified. These genes characterize common responses to CR, which consist of both activation and inhibition of stress-response pathways. With respect to liver tissue, transcriptional effects of CR exhibited surprisingly little overlap with those of aging, and a variable degree of overlap with the potential CR-mimetic drug resveratrol. These analyses shed light on the systemic transcriptional activity associated with CR diets, and also illustrate new approaches for comparative analysis of microarray datasets in the context of aging biology.
Insights
Caloric restriction (CR) impacts gene expression across multiple tissues, revealing common stress-response pathways. This study identifies 28 shared genes, offering insights into CR
Area of Science:
- Genomics and Aging Biology
- Transcriptional Regulation
Background:
- Caloric restriction (CR) is known to extend lifespan and delay age-related diseases in mammals.
- Previous studies focused on CR's effects on gene expression in specific tissues, but systemic effects remain less explored.
Purpose of the Study:
- To comparatively analyze the systemic effects of CR on gene expression across 10 different tissue types.
- To identify genes commonly affected by CR across multiple tissues and characterize shared transcriptional responses.
Main Methods:
- Comparative analysis of existing microarray datasets from 10 distinct tissue types (liver, heart, muscle, hypothalamus, hippocampus, white adipose tissue, colon, kidney, lung, cochlea).
- Application of novel methods for cross-tissue data comparison.
- Identification of genes with conserved expression responses to CR.
Main Results:
- Identified 28 genes exhibiting the most shared expression response to CR across the analyzed tissues.
- These shared genes indicate common CR-induced responses involving both activation and inhibition of stress-response pathways.
- Transcriptional effects of CR in liver showed minimal overlap with aging and variable overlap with resveratrol.
Conclusions:
- CR induces systemic transcriptional changes involving conserved stress-response pathways.
- The study highlights novel approaches for comparative microarray analysis in aging research.
- CR's transcriptional impact in the liver is distinct from aging processes.

