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Natural cell-mediated cytotoxicity may be critical in. the resistance displayed by animals.and humans to tumors and various pathogenic microorganisms. Because the frequency of tumors and infections increases markedly in aging populations, we have compared the natural killer (NK) competence of lymphid tissues (spleen, bone marrow) and of peritoneal cells of young adult and aged mice. Spontaneous NK activity was much lower, and the rate of. target cell lysis was much less, in aged mice. The level of NK activitywas only modestly increased in old, compared to young, mice when they were exposed to Trypanosoma. muscwli, an organism that provides strong stimulation of NK activity. Restricted NK activity of aged mice was not attributable to suppressor cells. The NK effector cells in old mice were characterized as being nonadherent to plastic, completely susceptible to lysis by complement plus an antiserum against specificity NK 1.2, and only slightly affected by treatment with antiserum against specificity Thy-1.2. Two indirect methods were employed to assess the-relative frequency of splenic NK cells at the time of-maximal stimulation by T. musculi: a cytotoxicity assay-with antiserum against NK 1.2 and a binding assay involving monolayers of YAC-1 tumor target cells. Similar results were obtained in both assays, indicating that at maximal stimulation about 10% of the total spleen cells of both young and old mice were NK cells. We conclude (cautiously) that the functional efficiency of aged NK cells is impaired and that this -defect may account, in part, for reduced ability of aged individuals to resist certain types of cancer and certain pathogenic microorganisms.Many biological and medical scientists believe that the declining competence of the immune system is responsible, in part, for the progressive rise in the frequency of. neoplastic and infectious. diseases associated with biological aging. The veracity of this postulate could be better judged if more were known about the immunological processes involved in responses to, and reactions with, tumor cells and pathogenic organisms. One feature of the immune system that has received considerable -attention in recent years is that of spontaneous, or natural, cellmediated cytotoxicity, associated especially with the subset of lymphocytes termed "natural killer" (NK) (1, 2). A variety of tumors (3, 4) and several pathogens (5-7) have been found to be susceptible to NK cells. The most clear-cut example of the susceptibility of a pathogen to NK cells is that of the human pathogen Trypanosoma cruzi (7). In addition, a number of other protozoan parasites have been found to alter markedly the NK activity of lymphoid tissues of their hosts (8-12).At present, information about the status of NK cells and their functional capabilities in aging animals and humans is meager. In most strains of mice,-NK activity in lymphoid tissues is high-.est in mice that are 1-3 months of age and declines considerably thereafter (13)(14)(15). Little is known about-NK cells and activity...

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