Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Investigating the specific core genetic-and-epigenetic networks of cellular mechanisms involved in human aging in peripheral blood mononuclear cells

Cheng-Wei Li, Wen-Hsin Wang and Bor-Sen Chen _

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Oncotarget. 2016; 7:8556-8579. https://doi.org/10.18632/oncotarget.7388

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Abstract

Cheng-Wei Li1, Wen-Hsin Wang1 and Bor-Sen Chen1

1 Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, Taiwan

Correspondence to:

Bor-Sen Chen, email:

Keywords: human aging, genetic-and-epigenetic network, anti-ageing drugs, microRNAs, DNA methylation, Gerotarget

Received: December 31, 2015 Accepted: February 03, 2016 Published: February 14, 2016

Abstract

Aging is an inevitable part of life for humans, and slowing down the aging process has become a main focus of human endeavor. Here, we applied a systems biology approach to construct protein-protein interaction networks, gene regulatory networks, and epigenetic networks, i.e. genetic and epigenetic networks (GENs), of elderly individuals and young controls. We then compared these GENs to extract aging mechanisms using microarray data in peripheral blood mononuclear cells, microRNA (miRNA) data, and database mining.

The core GENs of elderly individuals and young controls were obtained by applying principal network projection to GENs based on Principal Component Analysis. By comparing the core networks, we identified that to overcome the accumulated mutation of genes in the aging process the transcription factor JUN can be activated by stress signals, including the MAPK signaling, T-cell receptor signaling, and neurotrophin signaling pathways through DNA methylation of BTG3, G0S2, and AP2B1 and the regulations of mir-223 let-7d, and mir-130a. We also address the aging mechanisms in old men and women. Furthermore, we proposed that drugs designed to target these DNA methylated genes or miRNAs may delay aging. A multiple drug combination comprising phenylalanine, cholesterol, and palbociclib was finally designed for delaying the aging process.


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