Date of Award

5-31-2022

Document Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Catherine D. McCusker

Second Advisor

Kellee R. Siegfried

Third Advisor

Douglas C. Woodhams

Abstract

The Mexican axolotl is capable of regenerating various parts of its body and maintains this capacity throughout its entire life. Although this ability is sustained through adulthood, multiple regenerative processes appear to be negatively affected by aging. Here, we focus on evaluating the effect of aging on the rate of wound healing and limb regeneration. We have developed new in vivo, and ex vivo assays to characterize wound healing and identify differences between young and aged animals during this process. We have also characterized morphological features of mature skin from both groups of animals and although there are no obvious differences, the dermal layers are significantly thicker in aged animals. We discovered that aged animals progress through each stage of limb regeneration significantly slower than their young counterparts using two different in vivo regenerative assays. Moreover, we discovered that the most impacted stage was the early, dedifferentiation stage of limb regeneration. To further explore a potential explanation for this, expressional analysis of regenerative markers in pre-blastemal tissues revealed elevated levels of BMP2 in young animals. Expressional analysis on mature tissue revealed that ECM2 and TORAIP1, both markers that have been shown to be differentially expressed in young and aged mammalian fibroblasts, are expressed abundantly in young animals. Altogether, our studies show that the regenerative capacity of the Mexican axolotl can be leveraged to study the effects of aging on more complex regenerative processes.

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