Date of Award

5-1-2024

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biological Sciences

Dissertation/Thesis Chair

Melinda Larsen

Committee Members

Morgan Sammons, Andrew Berglund

Keywords

Cellular Senescence, MiRNAs (miRNAs), Salivary Glands, Salivary Hypofunction, Senescence Associated Secretory Phenotype (SASP), Sjögren's Disease

Subject Categories

Biology

Abstract

Cellular senescence, a triggered permanent cycle arrest, occurs with aging and is a component of many aging-related diseases. Triggers for senescence may include pathways involving DNA damage, telomere dysfunction, release of reactive oxygen species, and other additional internal/external stimuli. Senescence can have a positive effect as it plays a fundamental role in wound healing, tumor suppression, and promoting embryonic development. However, a prolonged consequence of senescence is the production of the senescence-associated secretory phenotype (SASP), in which the cell secretes pro-inflammatory and pro-tumorigenic factors that can have adverse effects on surrounding cells, which is known as the bystander effect. Eliminating senescent cells with therapeutics known as senolytic drugs can positively affect organ function in many contexts, including the salivary gland, where elimination of senescent cells can promote saliva production in animal models. Minimizing SASP factor expression by senescent cells with senomorphic agents can also positively affect organ function. miRNAs are known to regulate the expression of SASP factors and offer possible therapeutic targets for novel senomorphic drugs. Understanding pathways regulating senescence and SASP factor production will aid in discovering new therapeutic avenues and refine existing technologies and treatments.

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