Date of Award

2017

Document Type

Dissertation/Thesis

Submission Date

October 2026

Thesis/Dissertation Advisor [Chair]

Wetterer, James K.

Abstract

Autophagy, the cellular “recycling system” of unnecessary components, is a crucial mechanism for maintaining homeostasis inside the cell. Whereas impaired DNA repair function leads to accelerated aging and an early onset of several age-related diseases, it is not known whether autophagy plays a mediating role in this process. Here, we examined changes in autophagy in cells with progeria due to a disabled ERCC1-XPF, a nuclear DNA repair enzyme. We found that loss of ERCC1 function leads to DNA damage and a decrease in autophagic flux in cells. Low dose treatment with Rapamycin, an autophagy inducer, improved proliferation and delayed aging, or cellular senescence, in the cells. These data suggest that persistent DNA damage suppresses autophagic flux, thus contributing to early senescence and accelerated onset of age-related diseases. Therefore, therapeutics that improve autophagic flux, may prove beneficial for progeroid patients.

Comments

Includes bibliography.

Extent

29 p.

Identifier

FA00012630

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