John P. Richie, Jr., Ph.D. Professor of Public Health Sciences and Pharmacology, Penn State University College of Medicine.
Dr. John P. Richie
Dr. Richie is Professor of Public Health Sciences and Pharmacology at Penn State University College of Medicine in Hershey, PA. For the past 30 years, his research goal has been to understand the link between the biological aging process and the development of aging-related diseases and disorders including cancer. Using an interdisciplinary research approach, he focuses on the role of oxidative stress, generated both endogenously and from environmental exposures, as a mechanism for enhanced susceptibility during aging. His research has also investigates the impact of both endogenous and dietary antioxidants in protection against oxidative stress and its resulting damage, with the ultimate goal of designing and developing targeted prevention strategies.
Dr. Richie received his Ph.D. in Biochemistry from the University of Louisville in 1985. Prior to joining Penn State College of Medicine, he developed and led a Program on Cancer Susceptibility and Aging at the American Health Foundation (Institute for Cancer Prevention) in Valhalla, NY.
Abstract
Role of Glutathione in Aging and Disease Prevention
Glutathione (GSH) is the major endogenous intracellular antioxidant. Together with its associated enzymatic pathways, GSH plays numerous critical roles including protection of cells against oxidative stress, detoxification of toxins and carcinogens, post-translational regulation of protein function, and maintenance of immune function. Consequently, variation in GSH availability can have a substantial impact on cell and tissue integrity and function. Indeed, GSH depletion is common; occurring as a result of numerous disease processes, exposure to oxidants/drugs/toxicants, and changes in diet. The biological aging process is associated with a generalized depletion of GSH levels, a phenomenon which has been implicated as a possible mechanistic factor for a variety of aging-related impairments. Recently, genetic polymorphisms have been identified which affect the biosynthesis and tissues levels of GSH and are associated with altered risk for oxidative stress-related cancers.
Thus, increasing GSH represents a potentially important approach to counteract disorders associated with oxidative stress and aging. To this end, nutritional and pharmacological approaches have been tested with varying degrees of success. One potentially relevant approach is oral administration of GSH itself. This is supported by epidemiologic studies linking high dietary GSH intake with high blood levels and reduced risk for cancer and studies in animal models where orally administered GSH was found to be both bioavailable and effective at protecting against various aging-related disease processes. Despite this, its use in humans has been limited due to the lack of clinical data on its bioavailability and efficacy. However, in a recent double-blind, placebo-controlled trial, oral GSH was found to be effective at increasing body stores of GSH in a dose- and time-dependent fashion in healthy adults. Further, long-term GSH supplementation was associated with decreased levels of oxidative stress and increased immune function. These recent results further highlight the importance of GSH as an intervention target and the potential use of oral GSH to combat oxidative stress related pathologies.
