Date of Award

2017

Document Type

Dissertation/Thesis

Submission Date

October 2026

Thesis/Dissertation Advisor [Chair]

Niedernhofer, Laura

Abstract

DNA is damaged by many environmental factors like ultraviolet light from the sun and even by by-products of normal metabolism in our bodies, for example reactive oxygen species. A mouse model was used to test the effects DNA damage has on aging and age-related diseases. Damaged DNA is an early sign of muscle aging. The ERCC1- XPF complex is important because it repairs DNA. Using the Cre-Lox system, we knocked-out the Ercc1 gene in differentiated myocytes or muscle fibers. We measured body weight, fat content, muscle strength, and the ability of muscle to break down glucose, and found no comparable differences between the mutant and wild type mice. The histology also showed no significant difference between the two. These knockout mice only lived to be four to six months old, as oppose to the wild-type mice, which can live up to 35 months. Surprisingly, they died prematurely of heart disease. This demonstrates that cardiac muscle is more sensitive to DNA damage than skeletal muscle.

Comments

Includes bibliography.

Extent

23 p.

Identifier

FA00012622

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