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mucosal immunity. The GI mucosal immune response in the small intestine is a complex process that involves a series of events: antigen uptake and presentation of antigen at the mucosal surface by specialized epithelial cells (M cells) overlying Peyer’s patches in the small intestine, differentiation and migration of immunologically competent lymphocytes to the lamina propria, regulation of local antibody production in the intestinal wall, and mucosal epithelial cell receptor–mediated transport of antibodies to the intestinal lumen. The effect of aging on the first 2 steps, antigen uptake and presentation, is unclear.186 In rats, there was no change in the number of Peyer’s patches or the yield of lymphocytes per patch in small bowel. Increased T-suppressor/cytotoxic lymphocytes could explain the observed decrease in lamina propria immunoglobulin (Ig) A plasma cells, due to decreased cytokine-mediated differentiation of B lymphocytes by helper T cells.187 Animal studies also confirm that IgA plasma cell recruitment into the lamina propria is decreased in rats and macaque monkeys.188 Human studies have shown a significant decrease in T lymphocytes and mast cells in the rectal mucosa in normal individuals aged 55 years or older that was not reflected in other mucosal cell populations, such as neuroendocrine cells.189 Thus, the third step, differentiation and migration of lymphocytic immunoblasts into the lamina propria, seems to be decreased with aging. Interleukin-2 production in lamina propria lymphocytes and intestinal IgA production is decreased in aged subjects.190 A tissue-specific, age-associated reduction in transport of polymeric IgA across rat hepatocytes may be the result of decreased synthesis of polymeric Ig receptor or diminished microtubule-dependent translocation of the receptor-ligand complex. Data from the National Hospital Discharge Survey from 1979 to 1995 indicate that the total number of admissions for gastroenteritis decreased by 38%, mostly due to a decrease in the younger groups. Hospital admissions actually increased in those aged older than 75 years during this same period.191 The increase in incidence and severity of GI infectious diseases in the elderly may represent a relative immunodeficiency state of the GI immune system. Other factors that probably contribute to an increased risk of GI infection in older patients include improper food storage, decreased taste and smell (problems identifying contaminated food), dementia, reduced gastric acid, and colonic slowing. Diarrhea causes significant morbidity and mortality in older individuals, with 51% of deaths due to diarrhea in the United States occurring in patients older than 75 years. In addition to decreasing exposure to infectious environmental agents, novel interventions aimed at improving GI immunity may have a significant impact on morbidity and mortality caused by infectious disease in the elderly. Aging and GI Drug Metabolism An evolving area of interest to clinicians and investigators is the field of age-associated changes in drug metabolism. Elderly patients are at increased risk for drug interactions and adverse drug reactions, primarily due to known side effects of the large number of drugs prescribed in this age group.192 The cytochrome P450 system plays an essential role in drug metabolism in humans. The CYP3A subfamily expressed in the GI tract and liver is the most abundant form of hepatic cytochrome P450. It oxidizes a wide variety of clinically and toxicologically important agents, including endogenous and exogenous steroids, and activates procarcinogens such as aflatoxins.