ORCID

https://orcid.org/0009-0005-2754-562X

Date of Award

Spring 2025

Language

English

Embargo Period

4-29-2027

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biological Sciences

Program

Biology

First Advisor

Melinda Larsen

Committee Members

Melinda Larsen, Paolo Forni, Mehmet Yigit

Keywords

Cellular Senescence, Iron Oxide Nanoparticles, Sjögren's Disease, Inflammation, Fibrosis, Antagomirs

Abstract

Cellular senescence is known to be a root cause of multiple aging related diseases, as the cells are under permanent cell cycle arrest and therefore can no longer replicate. Affected cells produce a senescence-associated secretory phenotype (SASP) response, signaling to nearby cells that they are under this condition. A variety of molecules are released and expressed under this SASP response, including cytokines, chemokines, proteases, and growth factors. These molecules contribute to moderate inflammation, induction of fibrosis, and the creation of new senescent cells due to the bystander effect. Currently, two main classifications of drugs are employed to remedy cases where cellular senescence is causing tissue dysfunction. Senolytic drugs act to eliminate senescent cells from the body which can provide relief and delay the aging process, whereas senomorphic drugs work to inhibit the release of SASP factors into the surrounding environment, decreasing the spread of senescence within tissues to improve organ function and reduce inflammation. The SASP of senescent cells is modulated by a series of microRNAs (miRNAs), contributing to key factors of the phenotype such as permanently stabilizing cell cycle arrest, suppression of proteins, acceleration of the senescence process, and bolstering inflammation to the surrounding area. These miRNAs of interest can then be targeted by senescence associated drugs, and antagomirs (anti-miRs) can be delivered into senescent cells with the assistance of iron nanoparticles for therapeutic purposes. This thesis seeks to establish consistent methods of detecting and inducing senescence, and additionally, devise a strategy for the delivery of iron nanoparticle constructs into senescent cells. Obtaining a greater understanding of the senescence process and the chemical makeup of the SASP can accelerate the development of innovative and novel therapeutic options for affected individuals.

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Available for download on Thursday, April 29, 2027

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