Effects of calorie restriction and omega-3 dietary fat on aging in short- and long-lived rodents

Aging is accompanied by a steady increase in the incidence of spontaneous t umors and a decline in immune function. Calorie restriction (CR)or suppleme ntation with omega-3 fats prolongs life span, suppresses tumorigenesis, and ameliorates immune function in a variety of experimental models. We sugges t that decreased oxidant stress and upregulation of apoptosis mediate the e ffects of calorie restriction on immunity and longevity. CR prolongs life s pan in several animal models and our studies have examined the effects of C R on the immune system and on tumorigenesis. CR maintains naive T cells, pr events the rise in "double-negative" T cells, maintains lymphocyte responsi veness to mitogens, and preserves Dexamethasone induced apoptosis in spleen cells of MRL/lpr mice. CR also modulates the expression of inflammatory me diators and cytokines. CR decreases the Sjogren's syndrome-like chronic inf lammation of salivary glands of B/W animals while increasing expression of the immunosuppressive cytokine TGF beta 1 and decreasing expression of the pro-inflammatory cytokines IL-6 and TNF alpha. The autoimmune disease in th e B/W mouse also affects the kidneys, and we fi nd that renal expression of platelet derived growth factor-A, (PDGF-A) and thrombin receptor are decre ased in CR animals. Similarly, CR decreases the expression and localization of plasminogen activator inhibitor type 1 in glomeruli of B/W animals. CR also modulates expression and function of androgen receptors and the bindin g of insulin to liver nuclei. Finally, CR suppresses the development of bre ast tumors in the Ras oncomouse. These effects of calorie restriction are p aralleled in shout-lived B/W animals fed diets supplemented with omega-3 fa tty acids. Omega-a fatty acids induce the expression of hepatic antioxidant enzymes, and enhance apoptosis in lymphocytes of B/W animals.