Abstract
Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer’s Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer’s Disease.
Highlights
Aging is a natural biological process for all the species. It is associated with degenerative loss of tissue or cellular functions in the brain [1, 2], which increases the risk for neurological diseases, such as Parkinson’s Disease (PD), Alzheimer’s Disease (AD) and many other conditions [3]
We observed 1243 DNA methylation sites and 2743 genes to be shared by at least three regions at a cutoff of |r| > 0.3. These genes were defined as aging related genes and they were used for analysis step
The results from two data sets were compared and the overlapping results were showed in S1 Fig. In the frontal cortex (FCTX) region, we found 1297 DNA methylation sites, about > 50% of aging related sites in GSE15745, to be observed in GSE30272 (p < 2.2e − 16)
Summary
Aging is a natural biological process for all the species. It is associated with degenerative loss of tissue or cellular functions in the brain [1, 2], which increases the risk for neurological diseases, such as Parkinson’s Disease (PD), Alzheimer’s Disease (AD) and many other conditions [3]. Aging is viewed as a complex biological process [5]. In GenAge database [10], 298 genes have been collected from published works for their relationship with aging. Even with such knowledge, the PLOS ONE | DOI:10.1371/journal.pone.0150624. The PLOS ONE | DOI:10.1371/journal.pone.0150624 March 3, 2016
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