August 16, 2017

Understanding Cellular Senescence to Delineate the Aging Process

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Dr Kar and Poster

Upendra K Kar1, PhD, Jonathan A Laryea2, MD, William C Mustain2, MD, Jason Scott Mizell2, MD, Dr. Martin Hauer-Jensen1  , and Dr. Daohong Zhou1  Division of Radiation Health, Department of Pharmaceutical Sciences, 2Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR

Ageing leads to a progressive deterioration of structure and function of all organs over the time. The progressive accumulation of senescent cells and impairment of stem cells i.e. decline in their ability to maintain homoeostasis is well known in aging. Intestinal homeostasis is regulated by proliferation and differentiation of cycling intestinal stem cells (ISCs). ISCs are nested within a niche consisting of a wide variety of cell types including immune cells, mesenchymal fibroblasts & myofibroblasts, and endothelial cells. Niche-generated signals work in a concert with intrinsic stem cell properties to regulate the stem cell behavior. Senescence of endothelial cells leading to impairment in vascular functionality and neo-angiogenic capability is well documented. In this study we investigated the biological changes in endothelial cells induced to senescence by irradiation. Human Umbilical Vein Endothelial Cells (HUVEC) were exposed to various doses of irradiation i.e. 2Gy to 10Gy. The induction of senescence was noted by BrdU incorporation and senescence-associated β galactosidase” (SA-β-gal) staining.

Induction of senescence led to up regulation of Reactive Oxygen Species (ROS) level which was investigated by MitoSOX Red, peroxidized lipid sensor BODIPY and superoxide anion radicals (DHE MFI). Interestingly these senescent cells also displayed increase in DNA damage which was revealed by γH2AX foci assay. Senescence lead to induction of inflammation, impairment in tissue regenerative processes and immune-mediated clearance. As these features are the hallmark of aging research on senesce is on forefront, because understanding senescence will open the doors to understand the complexity of aging.

This work was supported by Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number “P20 GM109005” and Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number U1QHP28723.

References:
1. Methods Mol Biol. 2017;1612:97-105. doi: 10.1007/978-1-4939-7021-6_7.
2. Nat Med. 2016 Jan;22(1):78-83. doi: 10.1038/nm.4010. Epub 2015