Frydman, Sylvia

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.

Aging is the number one risk factor for numerous chronic diseases driving increased morbidity and healthcare costs globally. Thus, finding ways to uncouple chronical aging with risk of disease is imperative. Extensive evidence links aging with increased oxidative stress. The free radical theory of aging posits that reactive oxygen species (ROS) increase with age and cause oxidative damage to cellular components, thereby driving aging. In support of this, overexpressing the endogenous antioxidant catalase specifically in mitochondria (mCAT transgene) improves health and lifespan of mice. I hypothesized that if ROS is a root cause of aging then the mCAT transgene would slow aging in a murine model of a human progeroid syndrome (Ercc1-/Δ mice). Unfortunately, mCAT expression was not highly expressed in all tissues. Nevertheless, mCAT+/-;Ercc1-/Δ mice showed improvements in functional tests and health evaluations relative to Ercc1-/Δ mice supporting the conclusion that ROS plays an important causal role in aging.
matching, pre-transplant assessments and allocation of organs. In addition, I will discuss
ethical principles that can be used to aid transplant teams in the difficult task of allocating of
organs. I will also evaluate alternative options to the current transplant process such as an
opt-out vs. an opt-in system and controlled financial payment for organs. Finally, I will
analyze current policies regarding living donors and suggest avenues for future research into
alternative resources for organs.