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Competitor Christiaan Leeuwenburgh

Our general research interest is in the area of free radical biology and aging. Aging and several diseases including cardiovascular disease, diabetes, and neurodegenerative diseases are thought to result from increased formations of reactive oxygen species and reactive nitrogen species (aka, free radicals) resulting in oxidative stress. Reactive oxygen species are highly reactive molecules that cause damage to plasma membranes, enzymes, glucose molecules, and DNA. We are particularly interested in the oxidative mechanisms of aging and the effects of these during the aging process (i.e. mitochondrial dysfunction, apoptosis).

Mitochondiral oxidative stress with aging may be liked to apoptosis. Apoptosis is a highly regulated form of cell death characterized by specific morphological, biochemical, and molecular events. However, its role during aging, particularly in post mitotic tissues such as the brain, heart and skeletal muscle has not been studied in depth. Apoptosis appear to increase in post-mitotic tissues with age and it may be a major contributing factor to the observed loss in tissue function with age. The mechanisms by which apoptosis are induced with advancing age and adaptations that may protect against apoptosis remain to be identified, however. Moreover, the adaptations of major regulatory proteins upon the activation of the apoptotic signal transduction pathways during normal aging are unknown. Caloric restriction - an intervention that reduces oxidant production, improves calcium handling, reduces cell loss and extends maximum life span - could be emplyed to further study the anti-apoptotic adaptations. In addition, skeletal and heart muscle function with age could relate to apoptosis and apoptosis may be attenuated by caloric restriction. Further research would allow us to understand the mechanisms of apoptosis in vivo with normal aging, and caloric restriction.