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BRIDGING THE AGING-DISEASE DICHOTOMY. I. THE AMYLOIDOSIS MODEL HERMAN T. BLUMENTHAL* and BHARTUR N. PREMACHANDRAt Defining the Dichotomy Most biological and medical scientists, including those in gerontology, regard aging and the diseases of the aged as separate entities. According to this doctrine biological aging is characterized by expressions such as "intrinsic," "irreversible," "progressive," "universal," and "genetically programmed" [I]. The diseases of the aged (pathological aging) are distinguished from biological aging phenomena on the basis that these diseases are not genetically programmed and are reversible (at least potentially curable), and that no single disease is universal, that is, present in all species or in all aged subjects. Accordingly, all of the diseases prevalent in the aged are believed to derive primarily from external causes. Nevertheless, some connections between biological and pathological aging are recognized. Pathological aging is considered to be due to a long latent period following exposure to an extrinsic agent, to repeated insults from such agents over many years, and/or to the deterioration with age of intrinsic mechanisms that protect against disease. Conversely , it is also believed that disease may have the effect of intensifying or accelerating biological aging processes. Hence, there is an aging-disease dichotomy that holds that biological and pathological aging are essentially independent phenomena, but that they may impinge on one another. This dichotomy also implies that, if the diseases of the aged could be eliminated, each population cohort would die within a short span of time of some genetically programmed This investigation was supported, in part, by the Veterans Administration and the Narveen Medical Research Foundation, St. Louis, Missouri. ?Department of Community Medicine, St. Louis University School of Medicine, and Department of Psychology, Washington University, Campus Box 1125, One Brookings Drive, St. Louis, Missouri 63130.¦fVeterans Administration Medical Center, Jefferson Barracks, St. Louis, Missouri 63125. (Reprint requests should be addressed to Dr. Premachandra.)© 1990 by The University of Chicago. AU rights reserved. 003 1-5982/90/3303-0672101 .00 402 I Herman T. Blumenthal and Bhartur N. Premachandra ¦ Aging-Disease Dichotomy aging (nondisease) phenomenon [2]. Since, unlike diseases caused by microorganisms, no single primary cause can be identified for each of the degenerative and neoplastic diseases ofthe aged, a multifactorial risk factor concept that serves as a substitute for etiology has been adopted. Although the identification of risk factors is based to a great extent on statistical associations, they are often referred to by both medical scientists and the news media as "causes." However, even infectious diseases are multifactorial, since exposure to a pathogenic organism does not inevitably result in a disease process; other conditions need to be satisfied [3]. Nevertheless, while host factors may play a role in determining whether a subject develops an infectious disease, the infectious agent remains a sine qua non for disease manifestation . With the possible exception of certain viruses, no counterpart to the role of microorganisms has been identified in the genesis of the degenerative and neoplastic diseases of the aged. Moreover, it appears highly unlikely that such a counterpart exogenous agent can be found. The list of risk factors for diseases of the aged has grown almost geometrically in recent years [3] and need not be recited here. The same risk factor may be associated with more than one disease, as in the association of cigarettes with some cancers, with emphysema, and with coronary heart disease—disorders widely divergent in their pathological manifestations. A risk factor for one disease may be protective for another . There are data suggesting that factors that increase the risk of coronary heart disease may reduce the risk of certain cancers [4]. Moreover , there are many individuals with a history of prolonged exposure to certain risk factors who do not develop the diseases associated with them, and, conversely, there are individuals with little or no known exposure to risk factors for coronary heart disease or cancer who, nonetheless , develop these diseases—usually on an inherited basis or at an advanced age [5, 6]. Finally, in this regard, in studies in which mortalities from coronary heart disease have been reduced by diet and/or drugs, there has been little or no overall reduction in all-cause mortality. Instead , death from coronary heart...


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