Decrease by chronic energy intake restriction of cellular proliferation in the intestinal epithelium and lymphoid organs in autoimmunity-prone mice

Abstract

In previous studies we demonstrated that chronic energy intake restriction (CEIR) by a diet relatively low in fat, relatively high in carbohydrate, and reduced 40% in total calories extends life span and delays development of autoimmune disease in autoimmunity-prone mice. To investigate a possible cellular basis for this dramatic action of CEIR, we analyzed the rate of incorporation of [3H]thymidine by cells of the intestinal epithelium, thymus, spleen, and mesenteric lymph nodes in ad libitum-fed mice vs. CEIR mice of three autoimmunity-prone strains. In New Zealand Black (NZB), MRL/MP-lpr/lpr (MRL/lpr), and BXSB mice, CEIR slowed the rate of uptake of [3H]thymidine and, by inference, the rate of cellular proliferation among epithelial cells along the entire length of the gastrointestinal tract. Furthermore, CEIR decreased the apparent proliferative rate of lymphoid cells of the thymus, spleen, and mesenteric lymph nodes. This action by CEIR on the proliferative rate of cells of these rapidly replicating cell populations may point to an important mechanism by which calorie restriction inhibits the development of autoimmune disease and extends longevity in autoimmunity-prone mice.