Yousefzadeh, Matt

Aging is associated with chronic diseases and is attributed to increased morbidity, mortality, and healthcare costs globally. Controversy exists over the root cause(s) of aging, nonetheless, extensive research links increased oxidants and reduced antioxidant buffering capacity with aging. The free radical theory of aging posits that the toxic build-up of free radicals and reactive oxygen species (ROS), promotes oxidative stress and enhances aging. Investigations involving the effect of mitochondrial-targeted catalase, have proven to be beneficial in reducing ROS and increasing lifespan in naturally aged mice. My project involves investigating the biological benefit of the mCAT transgene and rescue of age-related functional decline in progeroid Ercc1-/∆ mice, an accelerated mouse model of aging. mCAT expression was shown to be largely restricted to the brain, heart, and muscle of mice. mCAT+/-;Ercc1-/∆ mice showed improvements in behavioral tests and health evaluations relative to controls.

Xeroderma pigmentosum (XP) is a disease caused by defects in gene products involved in nucleotide excision repair (NER) and lesion bypass. Individuals with XP are unable to repair DNA damage caused by UV light and thus are extremely sensitive to sunlight. XP is generally diagnosed by measuring unscheduled DNA synthesis (UDS) in response to UV irradiation of cells. Low levels of UDS indicate a low or nonexistent capacity for NER and leads to diagnosis of XP. This is typically done using autoradiography or a fluorescence assay on adherent fibroblasts collected from the patient. However, these methods are time and energy intensive, taking up to three months for results. My project involves development of an assay that uses fluorescently labelled nucleotides and flow cytometry to measure UDS in peripheral blood mononuclear cells. This assay gives results in 24 hours, allowing for more rapid diagnosis of XP.