BMP4, SGSH, and SLC11A2 are Predicted to Be Biomarkers of Aging Associated with Programmed Cell Death.

Abstract

Most neurodegenerative diseases are exacerbated by aging, with symptoms often worsening over time. Programmed cell death (PCD) is a controlled cell suicide mechanism that is essential for the stability, growth, and homeostasis of organisms. Understanding the effects of aging at the level of systems biology could lead to new therapeutic approaches for a broad spectrum of neurodegenerative diseases. In the absence of comprehensive functional studies on the relationship between PCD and aging of the prefrontal cortex, this study provides prefrontal brain biomarkers of aging associated with PCD that could open the way for improved therapeutic techniques for age-related neurodegenerative diseases. To this end, publicly available transcriptome data were subjected to bioinformatic analyses such as differential gene expression, functional enrichment, and the weighted gene coexpression network analysis (WGCNA). The diagnostic utility of the biomarkers was tested using a logistic regression-based prediction model. Three genes, namely BMP4, SGSH, and SLC11A2, were found to be aging biomarkers associated with PCD. Finally, a multifactorial regulatory network with interacting proteins, transcription factors (TFs), competing endogenous RNAs (ceRNAs), and microRNAs (miRNAs) was constructed around these biomarkers. The elements of this multifactorial regulatory network were mainly enriched in BMP signaling. Further exploration of these three biomarkers and their regulatory elements would enable the development of 3PM (predictive, preventive, and personalized) medicine for the treatment of age-related neurodegenerative diseases.