Abstract:Aging is accompanied by a steady increase in the incidence of spontaneous tumors and a decline in immune function. Calorie restriction (CR) or supplementation with (0-3 fats prolongs life span, suppresses tumorigenesis, and ameliorates immune function in a variety of experimental models. We suggest that decreased oxidant stress and upregulation of apoptosis mediate the effects of calorie restriction on immunity and longevity. CR prolongs life span in several animal models and our studies have examined the effe… Show more
AR. Is whole grain intake associated with reduced total and cause-specific death rates in older women? The Iowa Women's Health Study. Am J Public Health 1999 Mar;89(3):322-329. Lye M. A geriatric educational resource [letter]. Gerontology 1999;45(2):120. FS. Control of replicative life span in human cells: barriers to clonal expansion intermediate between Ml senescence and M2 crisis.
AR. Is whole grain intake associated with reduced total and cause-specific death rates in older women? The Iowa Women's Health Study. Am J Public Health 1999 Mar;89(3):322-329. Lye M. A geriatric educational resource [letter]. Gerontology 1999;45(2):120. FS. Control of replicative life span in human cells: barriers to clonal expansion intermediate between Ml senescence and M2 crisis.
Caloric restriction (CR) retards diseases and aging in laboratory rodents and is now being tested in nonhuman primates. One way to apply these findings to human health is to identify and test agents that may mimic critical actions of CR. Panel 2 focused on two outcomes of CR, reduction of oxidative stress and improved glucoregulation, for which candidate metabolic mimics exist. It was recommended that studies on oxidative stress should emphasize mitochondrial function and to test the efficacy of nitrone and other antioxidants in mimicking CR's effects. Studies should also focus on the long-term effects of compounds known to lower circulating glucose and insulin concentrations or to increase insulin sensitivity. Also, four other developing areas were identified: intermediary metabolism, response to infection, stress responses, and source of dietary fat. These areas are important because either they hold promise for the discovery of new mimetics or they need to be explored prior to initiation of CR trials in humans. Other recommendations were that transgenic approaches and adult-onset CR should be emphasized in future studies.
There is a strong association between aging, diet, and immunity. The effects of macronutrients and energy intake on splanchnic and hepatic lymphocytes were studied in 15 month old mice. The mice were ad-libitum fed 1 of 25 diets varying in the ratios and amounts of protein, carbohydrate, and fat over their lifetime. Lymphocytes in liver, spleen, Peyers patches, mesenteric lymph nodes, and inguinal lymph nodes were evaluated using flow cytometry. Low protein intake reversed aging changes in splenic CD4 and CD8 T cells, CD4:CD8 T cell ratio, memory/effector CD4 T cells and naïve CD4 T cells. A similar influence of total caloric intake in these ad-libitum fed mice was not apparent. Protein intake also influenced hepatic NK cells and B cells, while protein to carbohydrate ratio influenced hepatic NKT cells. Hepatosteatosis was associated with increased energy and fat intake and changes in hepatic Tregs, effector/memory T, and NK cells. Hepatic NK cells were also associated with body fat, glucose tolerance, and leptin levels while hepatic Tregs were associated with hydrogen peroxide production by hepatic mitochondria. Dietary macronutrients, particularly protein, influence splanchnic lymphocytes in old age, with downstream associations with mitochondrial function, liver pathology, and obesity-related phenotype.
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