My research program has focused on the role of oxidative stress and mitochondrial function in aging. We utilized a number of transgenic and knockout models with modified antioxidant defense systems to ask whether changes in antioxidant defense and oxidative stress modify lifespan as predicted by the long-standing Oxidative Stress Theory of Aging. In contrast to the predictions of this Theory, our studies have shown that modifying antioxidant defenses does not alter lifespan. These studies suggest that oxidative stress may not be a primary factor underlying aging per se. However, we propose the oxidative stress is indeed a critical factor in age-associated diseases such as sarcopenia and Amyotrophic Lateral Sclerosis (ALS). Our recent work has focused on the role of mitochondria and oxidative stress on alterations in the motor neurons, the neuromuscular junction and skeletal muscle that might contribute to the significant problem of age-related loss of muscle mass and may have implications for onset and progression of ALS.  In another line of research, we are studying the role of the mitochondrial unfolded protein response (mtUPR) in aging and the potential for tissue cross-talk based on mitochondrial signaling that might influence changes in metabolism.  As part of these studies, we are interested in studying age related changes in components of the mtUPR such as heat shock proteins and mitochondrial proteases Lon and ClpP.

My Publications