Macrophage migration inhibitory factor-knockout mice are long lived and respond to caloric restriction
Macrophage migration inhibitory factor-knockout mice are long lived and respond to caloric restriction
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DOI：
10.1096/fj.09-152223
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发表时间：
2010-07-01
期刊：
影响因子：
4.8
通讯作者：
Miller, Richard A.
中科院分区：
文献类型：
--
作者：
Harper, James M.;Wilkinson, J. Erby;Miller, Richard A.
巨噬细胞移动抑制因子(MIF)影响哺乳动物的炎症、葡萄糖动态平衡和细胞增殖。此前，我们发现MIF在包括卡路里限制(CR)在内的多种长寿小鼠模型中显著升高，这导致我们假设MIF在控制哺乳动物寿命方面可能是重要的，并且是CR延长寿命所必需的。为了验证这一假设，我们研究了在B6x129/Sv分离背景(MIF-KO)下，在随意喂养(AL)和CR条件下，Mif基因定向缺失的小鼠的寿命。将C57BL/6J雌鼠与129/SVJ雄鼠交配成F1杂交种，再将F1雄鼠与F1雌鼠杂交，产生具有正常MIF等位基因纯合的分离F2小鼠。MIF-KO小鼠不仅表现出对CR反应的寿命延长，而且在标准AL条件下，它们出人意料地比对照组活得更长。MIF-KO小鼠对致命性血管肉瘤有显著的保护作用，但比对照组更有可能死于播散性淀粉样蛋白，一种与年龄相关的炎症综合征。总体而言，这些数据驳斥了MIF是CR对寿命产生影响所必需的说法，但增加了MIF可能限制正常小鼠寿命的可能性。-Harper，J.M.，Wilkinson，J.E.，Miller，R.A.巨噬细胞移动抑制因子基因敲除小鼠活得很长，对热量限制有反应。FASE B J.24,2436-2442(2010)。Www.fasebj.org
Macrophage migration inhibitory factor (MIF) affects inflammation, glucose homeostasis, and cellular proliferation in mammals. Previously, we found that MIF was significantly elevated in multiple long-lived mouse models, including calorie restriction (CR), which led us to hypothesize that MIF might be important in the control of mammalian life span and be necessary for the life-extending effects of CR. To test this hypothesis, we examined the life span of mice with a targeted deletion of the Mif gene on a segregating B6 x 129/Sv background (MIF-KO) under ad libitum (AL) feeding and CR conditions. Control mice were generated by mating C57BL/6J females with 129/SvJ males to make an F1 hybrid, and crossing F1 males to F1 females to produce segregating F2 mice homozygous for the normal MIF allele. Not only did MIF-KO mice show a life span extension in response to CR, they were, unexpectedly, longer lived than controls under standard AL conditions. MIF-KO mice were significantly protected against lethal hemangiosarcoma, but more likely than controls to die of disseminated amyloid, an age-related inflammatory syndrome. Overall, these data refute the suggestion that MIF is required for the CR effect on life span, but raise the possibility that MIF may limit life span in normal mice.-Harper, J.M., Wilkinson, J.E., Miller, R.A. Macrophage migration inhibitory factor-knockout mice are long lived and respond to caloric restriction. FASEB J. 24, 2436-2442 (2010). www.fasebj.org