Aging is associated with an increased occurrence of infection and cancer, and, as people age, they begin to exhibit age-related immune deficiencies, collectively termed immunosenescence. To determine the effects of age on human monocytes, ‘aged monocytes’ (isolated from individuals > 65 years of age) were compared with ‘young monocytes’ (isolated from individuals -25 years of age) for their ability to be activated by lipopolysaccharide. Our results show that aged monocytes display a decrease in their cytotoxicity against tumor cells in vitro, a decrease in interleukin (IL1) secretion (although no decrease in IL1 precursor production was observed), a decrease in reactive oxygen and nitrogen intermediate (ROI/RNI) release, an increase in intracellular levels of cyclic adenosine monophosphate and a loss of protein kinase translocation. Therefore, aged monocytes present distinct characteristics of immunosenescence.
It is known that older people are more sensitive to cancer and infectious agents and need more time to recover from such disorders. Can this difference in sensitivity to cancer and infections between elderly and younger people be a result of a difference in their immune systems and, more specifically, in the way monocytes react to infectious agents and cancer cells? To determine what happens after cells have aged, human monocytes were purified from young donors (approximately 25 years of age) and from older donors (65 years of age or older) and tested for their ability to respond to the polyclonal activator LPS. Our results showed that monocytes from aged donors (aged monocytes), when compared with monocytes from younger donors (young monocytes) did lose part of their cytotoxicity against tumor cells (A375 human melanoma cells and L929 murine fibroblast cells). In addition, aged monocytes displayed a sharp decrease in IL-1 secretion, but did display the intracellular 31 kDa IL-1 precursor. Moreover, aged monocytes displayed a decrease in the production of reactive oxygen intermediates such as NO2 and H2O2. Finally, aged monocytes stimulated by LPS displayed an increase in intracellular cyclic AMP and have lost their protein kinase C translocation from the cytosol to the plasma membranes. These results suggest that age affects the immunologic and antitumoral properties of human monocytes.
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