Troyer D A, Venkatraman J T, Fernandes G
Age (Omaha). 1998 Oct;21(4):175-82. doi: 10.1007/s11357-998-0026-4.
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 ω-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 effects of CR on the immune system and on tumorigenesis. CR maintains naive T cells, prevents the rise in "double-negative" T cells, maintains lymphocyte responsiveness to mitogens, and preserves Dexamethasone induced apoptosis in spleen cells of MRL/Ipr mice. CR also modulates the expression of inflammatory mediators and cytokines. CR decreases the Sjögren's syndrome-like chronic inflammation of salivary glands of B/W animals while increasing expression of the immunosuppressive cytokine TGFβ1 and decreasing expression of the pro-inflammatory cytokines IL-6 and TNFα. The autoimmune disease in the B/W mouse also affects the kidneys, and we find that renal expression of platelet derived growth factor-A, (PDGF-A) and thrombin receptor are decreased 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 binding of insulin to liver nuclei. Finally, CR suppresses the development of breast tumors in the Ras oncomouse. These effects of calorie restriction are paralleled in short-lived B/W animals fed diets supplemented with ω-3 fatty acids. Omega-3 fatty acids induce the expression of hepatic antioxidant enzymes, and enhance apoptosis in lymphocytes of B/W animals.
衰老伴随着自发肿瘤发病率的稳步上升和免疫功能的下降。在各种实验模型中，热量限制（CR）或补充ω-3脂肪酸可延长寿命、抑制肿瘤发生并改善免疫功能。我们认为，氧化应激的降低和细胞凋亡的上调介导了热量限制对免疫和寿命的影响。CR在多种动物模型中延长寿命，我们的研究考察了CR对免疫系统和肿瘤发生的影响。CR可维持初始T细胞，防止“双阴性”T细胞增加，维持淋巴细胞对有丝分裂原的反应性，并保留地塞米松诱导的MRL/Ipr小鼠脾细胞凋亡。CR还可调节炎症介质和细胞因子的表达。CR可减轻B/W动物唾液腺类似干燥综合征的慢性炎症，同时增加免疫抑制细胞因子TGFβ1的表达，降低促炎细胞因子IL-6和TNFα的表达。B/W小鼠的自身免疫疾病也会影响肾脏，我们发现CR动物肾脏中血小板衍生生长因子-A（PDGF-A）和凝血酶受体的表达降低。同样，CR可降低B/W动物肾小球中纤溶酶原激活物抑制剂1型的表达和定位。CR还可调节雄激素受体的表达和功能以及胰岛素与肝细胞核的结合。最后，CR可抑制Ras致癌小鼠乳腺肿瘤的发生。在补充ω-3脂肪酸饮食的短命B/W动物中，热量限制的这些作用也有体现。ω-3脂肪酸可诱导肝脏抗氧化酶的表达，并增强B/W动物淋巴细胞的凋亡。
