Document Type

Technical Report

Date of this Version

8-2016

Publication Source

Frontiers of Aging Neuroscience

Volume

8

Issue

208

DOI

10.3389/fnagi.2016.00208

Abstract

Aging is a major risk factor for many neurodegenerative disorders. A key feature of aging biology that may underlie these diseases is cellular senescence. Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles. Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing. Senescence was induced in human fetal astrocytes by transient oxidative stress. Brain-expressed genes, including those involved in neuronal development and differentiation, were downregulated in senescent astrocytes. Remarkably, several genes indicative of astrocytic responses to injury were also downregulated, including glial fibrillary acidic protein and genes involved in the processing and presentation of antigens by major histocompatiblity complex class II proteins, while pro-inflammatory genes were upregulated. Overall, our findings suggest that senescence-related changes in the function of astrocytes may impact the pathogenesis of age-related brain disorders.

Copyright/Permission Statement

Originally published in Frontiers in Aging Neuroscience, an Open Access journal published under a Creative Commons Attribution (CC BY) license.

Keywords

astrocyte senescence, astrocyte function, brain aging, RNA sequencing, brain oxidative stress

 

Date Posted:10 July 2017

This document has been peer reviewed.