An in vitro model of caloric restriction
An in vitro model of caloric restriction
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DOI：
10.1016/s0531-5565(03)00055-x
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发表时间：
2003-06-01
影响因子：
3.9
通讯作者：
Lane, MA
中科院分区：
文献类型：
--
作者：
de Cabo, R;Fürer-Galbán, S;Lane, MA
热量限制（CR）延长寿命和增强压力反应能力的潜在机制仍然难以捉摸。由于使用动物进行 CR 研究和评估寿命作为 CR 有效性衡量标准的复杂性，该领域的进展缓慢。因此，开发 CR 的体外模型非常有意义。在这里，我们使用从自由采食 (AL) 或 CR 饮食的 Fisher 344 大鼠或恒河猴获得的血清来培养各种细胞类型。我们发现用 CR 血清处理培养细胞会导致细胞增殖减少，对氧化剂和热的耐受性增强，并提高应激反应基因的表达。这些表型特征反映了 CR 对动物的影响。在 CR 血清中补充胰岛素和胰岛素样生长因子 (IGF)-1 部分恢复了用 AL 血清培养的细胞中观察到的增殖和应激反应表型，表明胰岛素和 IGF-1 水平的降低可能导致 CR 相关效应。这种体外细胞培养模型概括了 CR 的关键体内增殖和应激反应表型特征，并进一步表明内分泌机制有助于在 CR 动物中观察到的应激反应能力增强。 (C) 2003 Elsevier Science Inc. 保留所有权利。
The mechanisms underlying the ability of caloric restriction (CR) to extend life span and enhance stress responsiveness remain elusive. Progress in this area has been slow due to the complexities of using animals for CR studies and assessing life span as the measure of CR effectiveness. It is therefore of great interest to develop in vitro models of CR. Here we use sera obtained from either Fisher 344 rats or Rhesus monkeys that were fed ad libitum (AL) or CR diets to culture various cell types. We show that treatment of cultured cells with CR sera caused reduced cell proliferation, enhanced tolerance to oxidants and heat, and heightened expression of stress-response genes. These phenotypic features mirror the effects of CR in animals. Supplementation of CR serum with insulin and insulin-like growth factor (IGF)-1 partially restored the proliferative and stress-response phenotype that was seen in cells cultured with AL serum, indicating that reduced levels of insulin and IGF-1 likely contribute to the CR-related effects. This in vitro cell culture model recapitulates key in vivo proliferative and stress-response phenotypic features of CR, and further suggests that endocrine mechanisms contribute to the enhanced stress responsiveness observed in CR animals. (C) 2003 Elsevier Science Inc. All rights reserved.