Aging Aging

Understanding Aging 117. Do long-lived cells selectively fail in humans?The answer to this question is certainly yes. The main sites in which clearage changes take place are in cells that cannot be replenished without a disruptionin their functions in the body. Key cell types are neurons, heart muscle,skeletal muscle, and certain hormone producing cells. The important precursorof both androgens and estrogens, DHAE, declines linearly with age in men andwomen and may well be a product of cells that are not replenishable. But evenmore obvious is the postmitotic nature of cells in the nervous system and othernonreplenishing tissues such as skeletal and heart muscle. Thus, damage to thecells making up these organs generally cannot be repaired through replacementbecause such postmitotic cells cannot be made to divide. In the case ofthe brain, continual replacement of old cells by new ones might preserve reflexbrain function, but most such newly incorporated nerve cells would replaceneurons in whose facilitated synapses useful memories had been stored. Thus,paradoxically, higher animals, particularly humans, age because some keykinds of cells they possess have long, but not indefinitely long, lifetimes.(Although it is fairly obvious I would like it to be called “The Strehler Paradox,”so that way I might be remembered for something unless a differentversion of the perpetual motion machine I proved unworkable actually generateduseful energy!)8. What are the underlying causes of the age-related decline in the immunesystem?The immune system consists of two major forms: innate and acquired. Innateimmunity comprises polymorphonuclear leukocytes, natural killer cells, andmononuclear phagocytes and utilizes the complement cascade as the main solubleprotein effector mechanism. This type of immunity recognizes carbohydrate structuresthat do not exist on eukaryotic cells; thus foreign pathogens can be detectedand acted against. Lymphocytes are the major cells involved in the system ofacquired immunity, with antibodies being the effector proteins. The T-cell receptor(TCR) and antibodies recognize specific antigenic structures.Deterioration of the immune system with aging (“immunosenescence”) isbelieved to contribute to morbidity and mortality in man due to the greaterincidence of infection, as well as possibly autoimmune phenomena and cancerin the aged. T lymphocytes are the major effector cells in controlling pathogenicinfections, but it is precisely these cells that seem to be most susceptibleto dysregulated function in association with aging.Decreases in cell-mediated immunity are commonly measured in elderlysubjects. By most parameters measured, T-cell function is decreased in elderlycompared to young individuals. Moreover, prospective studies over the yearshave suggested a positive association between good T-cell function in vitro and