de Cabo Rafael, Fürer-Galbán Stefanie, Anson R Michael, Gilman Charles, Gorospe Myriam, Lane Mark A
Laboratory of Experimental Gerontology, National Institute on Aging-Intramural Research Program, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA.
Exp Gerontol. 2003 Jun;38(6):631-9. doi: 10.1016/s0531-5565(03)00055-x.
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.
热量限制（CR）延长寿命和增强应激反应能力的潜在机制仍不清楚。由于使用动物进行CR研究以及将寿命作为CR有效性衡量指标的复杂性，该领域进展缓慢。因此，开发CR的体外模型具有很大的意义。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。我们表明，用CR血清处理培养的细胞会导致细胞增殖减少、对氧化剂和热的耐受性增强以及应激反应基因的表达增加。这些表型特征反映了CR在动物中的作用。用胰岛素和胰岛素样生长因子（IGF）-1补充CR血清部分恢复了用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水平降低可能导致与CR相关的效应。这种体外细胞培养模型概括了CR在体内的关键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CR动物中观察到的应激反应增强。
