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Effects of ROS and Aging on Cellular and Organ Function

Lynn, Andrew M. (2021) Effects of ROS and Aging on Cellular and Organ Function. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

In aged individuals, increased oxidative damage in cells leads to cellular decline and organ dysfunction. Since the mid-1950s, reactive oxygen species (ROS) have been implicated in age-related organ damage, including hepatic, cardiovascular, and renal disease. While this connection has been established for some time, the production and particularly the function of ROS within and between cells is still being studied. This review will examine what is known about the enzymatic and mitochondrial sources of ROS within cells, and explore their effect on age-related diseases in the liver, heart, and kidneys. Fibrosis and functional decline of each of these organs has been reported in animal models and clinical data. ROS including hydroxyl radicals (OH.), hydrogen peroxide (H2O2), and superoxide anion (O2-) are discussed as well as processes that produce them: P450 enzymes, xanthine oxidase, NADP oxidase, and the electron transport chain (ETC). While ROS are useful for cell signaling, accumulation of these species at high levels is damaging. This review will focus on the role of ROS on cell-signaling proteins including NF-κβ, TNF-α, and atrial natriuretic factor (ANF), as well as resulting mitochondrial DNA (mtDNA) damage. The modulation of these factors by high ROS prevalence, in addition to a decline in mtDNA damage repair capabilities over time, is the foundation of age-related oxidative stress. As such, implications of reductive enzymes including superoxide dismutase, catalase, and glutathione peroxidase are discussed as well.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lynn, Andrew M.aml208@pitt.eduaml2080000-0003-2144-608X
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorFolan, Maggiefolanm@pitt.edufolanm
Committee MemberSant, VinayakVIS45@pitt.eduVIS45
Committee MemberBirder, Lori Annlbirder@pitt.edulbirder
Date: 27 May 2021
Date Type: Publication
Defense Date: 22 April 2021
Approval Date: 27 May 2021
Submission Date: 17 May 2021
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 22
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: ROS, Aging, Antioxidant, Xanthine Oxidoreductase, Purine, Lower Urinary Tract
Date Deposited: 27 May 2021 18:34
Last Modified: 27 May 2021 18:34
URI: http://d-scholarship.pitt.edu/id/eprint/41108

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