Denham Harman

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The phenomenon of growth, decline and death—aging—has been the source of considerable speculation (1, 8, 10). This cycle seems to be a more or less direct function of the metabolic rate and this in turn depends on the species (animal or plant) on which are superimposed the factors of heredity and the effects of the stresses and strains of life—which alter(More)
Aging is the accumulation of changes that increase the risk of death. Aging changes can be attributed to development, genetic defects, the environment, disease, and an inborn process: the aging process. The latter is the major risk factor for disease and death after age 28 in the developed countries. In these countries, average life expectancies at birth(More)
Free radical reactions are ubiquitous in living things. Studies on the origin and evolution of life provide a reasonable explanation for the prominent presence of this unruly class of chemical reactions. These reactions have been implicated in aging. This phenomenon is the accumulation of changes responsible for the sequential alterations that accompany(More)
Aging is a universal process that began with the origination of life about 3.5 billion years ago. Accumulation of the diverse deleterious changes produced by aging throughout the cells and tissues progressively impairs function and can eventually cause death. Aging changes can be attributed to development, genetic defects, the environment, disease, and an(More)
Aging is the progressive accumulation of diverse, deleterious changes with time that increase the chance of disease and death. The basic chemical process underlying aging was first advanced by the free radical theory of aging (FRTA) in 1954: the reaction of active free radicals, normally produced in the organisms, with cellular constituents initiates the(More)
Epibatidine, a neurotoxin isolated from the skin of Epipedobates tricolor, is an efficacious antinociceptive agent with a potency 200 times that of morphine. The toxicity of epibatidine, because of its nonspecificity for both peripheral and central nicotinic receptors, precludes its development as an analgesic. During the synthesis of epibatidine analogs we(More)
Alzheimer's disease (AD) is the chief cause of dementia, and age is its major risk factor. The majority of cases (90-95%) are sporadic (SAD), and the remainder are familial (FAD). AD is characterized by two brain lesions, intraneuronal fibrillary tangles and extracellular plaques. The lesions are identical in SAD and FAD as well as to those in persons with(More)