Format

Send to

Choose Destination
Front Aging Neurosci. 2016 Aug 31;8:208. doi: 10.3389/fnagi.2016.00208. eCollection 2016.

Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence.

Author information

1
Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia PA, USA.
2
Department of Biology, Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia PA, USA.
3
Epigenetics Program, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
4
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.

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 histocompatibility 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.

KEYWORDS:

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

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center