Aging, drugs, and drug metabolism.

137 Translational I N this series of special themed editions of the Journal of Gerontology Biological Sciences and Medical Sciences, reviews and commentaries have been solicited that focus on the basic biology, animal models, translational research, physiology, epidemiology, and public health aspects of aging. This emphasizes the multidisciplinary and translational nature of modern aging research. Aging is stochastic, complicated , and complex; therefore, answers and solutions to the problems of old age will almost certainly require multidisciplinary teams that focus on translating research into outcomes that are ultimately beneficial for humans. In this edition, our theme is " Drugs and Drug Metabolism. " Why should biogerontologists be interested in drugs and drug metabolism? These topics would seem, superficially at least, to be very medical and quite distant from the cellular and physiological focus of most aging biologists. In fact, there are many reasons. First, old age is associated with marked changes in the response to medications, which are a consequence of age-related changes in both the pharmaco-kinetics and the pharmacodynamics of drugs. These pharmacological changes are caused by the same biological mechanisms as other aging changes, including altered gene expression, oxidative injury, and mitochondrial dysfunction (1). Thus, age-related changes in drug metabolism should be considered a typical phenotypic characteristic of the aging process. Generally, older age is associated with increased blood concentrations of drugs and altered metabolism, reduced effectiveness, and increased risk of adverse reactions for many medications (2). Impaired response to pharmacotherapeutic interventions is a critical yet underemphasized aspect of older age. If medical therapies for disease were effective in old age, then it would not matter that old age is the main risk factor for disease because diseases would still be able to be treated and cured. Impaired responsiveness to therapeutic interventions has such important implications for older people that we believe it should be included in any definition of aging. Furthermore, by studying the effects of old age on drug disposition, we can gain insights into the aging process itself. For example, age-related changes in the hepatic micro-circulation were discovered as a direct consequence of research into the effects of age on hepatic drug metabolism (3, 4). It should also be recognized that drug metabolism is only one aspect of the body's response to any potentially toxic and disease-causing xenobiotic. Therefore, age-related changes in drug metabolism and elimination have much broader implications for disease susceptibility. For example, …