MODULATION OF AGE-RELATED ALTERATIONS IN MEMBRANE-COMPOSITION AND RECEPTOR-ASSOCIATED IMMUNE FUNCTIONS BY FOOD RESTRICTION IN FISCHER-344 RATS

Food restriction is known to modulate aging and age-associated immune functions in rodents. In an attempt to understand the mechanism(s) thr ough which food restriction delays age-associated loss of certain immu ne functions, lipid composition of spleen cells as well as binding of spleen cells to interleukin-2 (IL-2) and insulin were analyzed in four month-old and 19-month-old ad libitum fed (AL) and food-restricted (F R) Fischer-344 male rats. The results revealed that although Al-fed ra ts did not show a difference in age-related changes for IL-2 and insul in binding, the number of binding sites were significantly increased i n the spleen cells of 19-month-old FR animals when compared with those of the 19-month-old AL group. When spleen cell phospholipid fractions were analyzed for fatty acid composition, the spleen cells from FR an imals consistently revealed higher linoleic acid (18:2) levels and sig nificantly lower arachidonic acid (20:4) and long chain fatty acid, do cosatetraenoic acid (22:4) levels in the phosphatidylcholine and phosp hatidylethanolamine fractions than the spleen cells of the AL rats. Fu rther, spleen cell plasma membranes of FR rats also exhibited similar changes showing higher 18:2 and lower 20:4 and 22:4 levels than the AL animals. Finally, spleen cells obtained from 19-month-old FR animals produced higher levels of IL-2 and lesser prostaglandin E2 when compar ed to 19-month-old AL animals. The above observations suggest that one of the mechanims through which food restriction may delay the loss of age-associated immune functions is through modulation of the fatty ac yl composition of phospholipid fractions of spleen cell membranes. Thi s modification may facilitate binding of IL-2 and insulin to their rec eptors and thus may improve T cell proliferation and prevent or delay age-related loss in immune functions.