Research Paper|Volume 8, Issue 5|pp 917—931

The effects of graded levels of calorie restriction: VII. Topological rearrangement of hypothalamic aging networks

Davina Derous^1,², Sharon E Mitchell¹, Cara L Green¹, Yingchun Wang³, Jing Dong J Han⁴, Luonan Chen⁵, Daniel E.L Promislow⁶, David Lusseau¹, John R Speakman^1,³, Alex Douglas^1,²

¹Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK
²Centre for Genome Enabled Biology and Medicine, University of Aberdeen, Aberdeen, Scotland, AB24 3RL, UK
³State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, 100101, China
⁴Chinese 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
⁵Key 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
⁶Department of Pathology and Department of Biology, University of Washington, Seattle, WA 98195, USA

Received: March 2, 2016Accepted: March 31, 2016Published: April 23, 2016

https://doi.org/10.18632/aging.100944

Copyright: © 2016 Derous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.