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.
Highlights
The nematode worm C. elegans had already been established as a useful model organism for studies of aging since it has a relatively short life span and can propagate populations of synchronized individuals
Some signaling pathways defined by each genetic factors which affect lifespan have been discovered, such as insulin/IGF-1-like signaling (IIS) pathway by a FOXO-family transcription factor DAF-16 [4]
Based on the Gene Set Enrichment Analysis (GSEA) approach, we have identified several significantly related genetic pathways during aging in C. elegans
Summary
The nematode worm C. elegans had already been established as a useful model organism for studies of aging since it has a relatively short life span and can propagate populations of synchronized individuals. Aging in C. elegans has been proposed to be caused by hyperfunction, that is, overactivity during adulthood of processes biosynthetic that contribute to development and reproduction. Such hyperfunction can lead to hypertrophy-associated pathologies, which cause the age increase in death [1]. Several mutated genes have been identified to extend lifespan by large-scale RNAi longevity screens in C. elegans [2]. Microarray technology has been widely used in the genome wide study of gene expression changes associated with aging in C. elegans and may provide some insights into potential mechanisms [5]. A lot of genes with specific changes www.impactaging.com
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