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

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.

miR-96, miR-145 and miR-9 expression increases, and IGF-1R and FOXO1 expression decreases in peripheral blood mononuclear cells of aging humans

“…In addition, fractionation followed by cell culturing could increase the number of cells, but we decided not to do so because this could affect the expression of miRNAs and genes. Another reason for studying changes in PBMC was that aging studies involving living humans are commonly carried out on blood cells and using PBMC allowed the comparison of our results with other data, both published [63–65] and yet to be published.…”

An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci

“…The G0S2 protein is well-known for its role in regulating lipid metabolism where it serves as a negative regulator of lipolysis [49,50]. It has been implicated in mechanisms of obesity, diabetes, aging, and cancer, and linked to gene networks involved in apoptosis, cell communication, and cell death [51]. Because of this, future investigations could examine a potential role of G0S2 in the well-established link between PTSD and metabolic disorders [52,53].…”

Investigating Pathogenic and Hepatocarcinogenic Mechanisms from Normal Liver to HCC by Constructing Genetic and Epigenetic Networks via Big Genetic and Epigenetic Data Mining and Genome-Wide NGS Data Identification

“…Therefore, the parameter vectors θ i ,PPIN and θ i ,GRN can then be obtained by solving the following constrained least square parameter estimation problems, respectively [ 52 ]: where the accuracies of the parameter estimations in ( 8 ) and ( 9 ) were given by the following error estimations and , respectively, and and represent the identified parameters. The solutions of the above problems, in which inequality constraints can guarantee the negative effect of miRNA regulation on genes and the positive basal levels of genes/proteins, can be obtained by applying the system identification method in MATLAB optimization toolbox using genome-wide mRNA expression data and DNA methylation profiles based on a reflective Newton method for minimizing a quadratic function [ 53 ].…”