The effects of graded levels of calorie restriction: VII. Topological rearrangement of hypothalamic aging networks.
Connectivity in a gene-gene network declines with age, typically within gene clusters. We explored the effect of short-term (3 months) graded calorie restriction (CR) (up to 40 %) on network structure of aging-associated genes in the murine hypothalamus by using conditional mutual information. The networks showed a topological rearrangement when exposed to graded CR with a higher relative within cluster connectivity at 40CR. We observed changes in gene centrality concordant with changes in CR level, with Ppargc1a, and Ppt1 having increased centrality and Etfdh, Traf3 and Abcc1 decreased centrality as CR increased. This change in gene centrality in a graded manner with CR, occurred in the absence of parallel changes in gene expression levels. This study emphasizes the importance of augmenting traditional differential gene expression analyses to better understand structural changes in the transcriptome. Overall our results suggested that CR induced changes in centrality of biological relevant genes that play an important role in preventing the age-associated loss of network integrity irrespective of their gene expression levels.
Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK.|Centre for Genome Enabled Biology and Medicine, University of Aberdeen, Aberdeen, Scotland, AB24 3RL, UK.
Davina
D
Derous
Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK.
Sharon E
SE
Mitchell
Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK.
Cara L
CL
Green
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, 100101, China.
Yingchun
Y
Wang
Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Jing Dong J
JD
Han
Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Luonan
L
Chen
Department of Pathology and Department of Biology, University of Washington, Seattle, WA 98195, USA.
Daniel E L
DE
Promislow
Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK.
David
D
Lusseau
Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK.|State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, 100101, China.
John R
JR
Speakman
Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK.|Centre for Genome Enabled Biology and Medicine, University of Aberdeen, Aberdeen, Scotland, AB24 3RL, UK.
Alex
A
Douglas
D000375:Aging / Q000235:genetics*; D000818:Animals; D031204:Caloric Restriction; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D051379:Mice; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics; D013869:Thiolester Hydrolases / Q000235:genetics; D059467:Transcriptome
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase
aging; calorie restriction; conditional mutual information; network biology; transcriptomics