Document Type

Journal Article

Department/Unit

Department of Biology

Title

Dynamic regulation of genetic pathways and targets during aging in Caenorhabditis elegans

Language

English

Abstract

Numerous genetic targets and some individual pathways associated with aging have been identified using the worm model. However, less is known about the genetic mechanisms of aging in genome wide, particularly at the level of multiple pathways as well as the regulatory networks during aging. Here, we employed the gene expression datasets of three time points during aging in Caenorhabditis elegans (C. elegans) and performed the approach of gene set enrichment analysis (GSEA) on each dataset between adjacent stages. As a result, multiple genetic pathways and targets were identified as significantly down- or up-regulated. Among them, 5 truly aging-dependent signaling pathways including MAPK signaling pathway, mTOR signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway and ErbB signaling pathway as well as 12 significantly associated genes were identified with dynamic expression pattern during aging. On the other hand, the continued declines in the regulation of several metabolic pathways have been demonstrated to display age-related changes. Furthermore, the reconstructed regulatory networks based on three of aging related Chromatin immunoprecipitation experiments followed by sequencing (ChIP–seq) datasets and the expression matrices of 154 involved genes in above signaling pathways provide new insights into aging at the multiple pathways level. The combination of multiple genetic pathways and targets needs to be taken into consideration in future studies of aging, in which the dynamic regulation would be uncovered.

Keywords

aging, C. elegans, pathways, network

Publication Date

2014

Source Publication Title

Aging

Volume

6

Issue

3

Start Page

215

End Page

230

Publisher

Impact Journals

DOI

10.18632/aging.100648

Link to Publisher's Edition

http://dx.doi.org/10.18632/aging.100648

ISSN (electronic)

19454589

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