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Access Type

WSU Access

Date of Award

January 2018

Degree Type

Thesis

Degree Name

M.S.

Department

Nutrition and Food Science

First Advisor

DIANE CRESS

Abstract

ABSTRACT

EXPLORING THE RELATIONSHIP BETWEEN CELLULAR SENESCENCE AND DNA POLYMERASEβ ΙΝ DOWN SYNDROME

by

BRIANNA PACE

May 2018

Advisor: Dr. Diane Cress

Major: Nutrition and Food Science

Degree: Master of Science

The goal of this paper is establish and evaluate the relationship between the accelerated aging and premature cellular senescence with the reduced DNA polymeraseβ observed in Down syndrome. Primary fibroblasts from Down syndrome individuals demonstrate greater SA-β-Gal staining (4-fold increase, p<0.001), increased p16 transcript abundance (3-fold increase, p<0.01), and reduced HMGB1 nuclear localization (1.5-fold lower, p<0.01) when compared to primary fibroblast from non-Down syndrome fibroblasts. These biomarkers of senescence establish the premature aging expected in a Down syndrome individual. DNA polymerase β (POLβ) expression is significantly reduced in Down syndrome primary fibroblasts (53% decline, p<0.01). While we are unable to definitely state a direct causal link between DNA polymeraseβ reduction and the precocious aging present, it is demonstrated that DNA polymeraseβ plays a role.

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