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Medical Physiology

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University of Kentucky

Theses/Dissertations

Aging

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Genetic Regulation Of Hematopoietic Stem Cell Aging, Erin J. Oakley Jan 2008

Genetic Regulation Of Hematopoietic Stem Cell Aging, Erin J. Oakley

University of Kentucky Doctoral Dissertations

It is well documented that both quantitative and qualitative changes in the murine hematopoietic stem cell (HSC) population occur with age. In mice, the effect of aging on stem cells is highly strain-specific, thus suggesting genetic regulation plays a role in HSC aging. In C57BL/6 (B6) mice, the HSC population steadily increases with age, whereas in DBA/2 (D2) mice, this population declines. Our lab has previously mapped a quantitative trait locus (QTL) to murine chromosome 2 that is associated with the variation in frequency of HSCs between aged B6 and D2 mice. In these dissertation studies, I first aim to …


Molecular Mechanisms Of Olfactory Neurodegeneration, Radhika Anand Vaishnav Jan 2007

Molecular Mechanisms Of Olfactory Neurodegeneration, Radhika Anand Vaishnav

University of Kentucky Doctoral Dissertations

Olfactory sensory decline has been associated with normal aging as well as neurodegenerative disorders, yet the underlying mechanisms are unclear. The overall aim of this dissertation was to investigate the fundamental molecular and cellular mechanisms associated with olfactory neurodegeneration. This investigation uses an integrative approach, combining proteomics and gene expression analyses with cellular and tissuelevel characterization. Using these approaches, two model systems were investigated: 1) normally aging C57BL/6 mice of ages 1.5-, 6- and 20-months; and 2) a mouse model of elevated endogenous oxidative stress-associated neurodegeneration, namely, the Harlequin mutant mouse. The first specific aim was to test the hypothesis …