Yang Hyunwon, Youm Yun-Hee, Nakata Chiaki, Dixit Vishwa Deep
Laboratory of Neuroendocrine-Immunology, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
Peptides. 2007 Oct;28(10):1931-6. doi: 10.1016/j.peptides.2007.07.030. Epub 2007 Aug 19.
Caloric restriction (CR) is the only preventive intervention that has robust pro-longevity effects in experimental models. Various circulating hormones that regulate the state of negative energy balance may drive the multi-system beneficial effects of the CR phenomenon. Ghrelin, one such stomach-derived circulating peptide hormone stimulates food intake, promotes GH release and inhibits pro-inflammatory cytokines. We have recently demonstrated that ghrelin also reverses age-related thymic involution. Here, we report that chronic CR in aging mice results in reduction in body weight, and spleen size but remarkably, leads to a significant increase in the size and weight of stomach. The increased size of stomach was largely due to increased size of fundus (forestomach) and also smaller but statistically significant enlargement of antrum. The analysis of serial stomach sections revealed that chronic CR leads to a striking hypertrophy of lamina propria, stratum basale, stratum corneum and the stratified squamous epithelium of forestomach of the aged animals. We also report for the first time that chronic CR during aging significantly increases circulating ghrelin levels as well as total ghrelin production in the stomach and reverses age-related loss of ghrelin receptor expression in pituitary. Our data suggests that long-term CR-induced increased ghrelin production from hypertrophic stomach in mice may be an adaptive survival strategy in response to sustained negative energy balance that triggers heightened state of food seeking. Taken together, these data provide new insights into the underlying mechanism behind the salutary effects of chronic caloric restriction during aging process.
热量限制（CR）是唯一在实验模型中具有显著延长寿命作用的预防性干预措施。各种调节负能量平衡状态的循环激素可能驱动了CR现象的多系统有益效应。胃饥饿素就是这样一种源自胃的循环肽激素，它刺激食物摄入、促进生长激素释放并抑制促炎细胞因子。我们最近证明，胃饥饿素还能逆转与年龄相关的胸腺退化。在此，我们报告，衰老小鼠的长期CR导致体重和脾脏大小减小，但值得注意的是，胃的大小和重量显著增加。胃大小的增加主要归因于胃底（前胃）大小的增加，以及胃窦较小但具有统计学意义的增大。对连续胃切片的分析显示，长期CR导致老年动物前胃固有层、基底层、角质层和复层鳞状上皮显著肥大。我们还首次报告，衰老过程中的长期CR显著提高了循环胃饥饿素水平以及胃中胃饥饿素的总产生量，并逆转了垂体中与年龄相关的胃饥饿素受体表达丧失。我们的数据表明，长期CR诱导的小鼠肥大胃中胃饥饿素产生增加可能是一种适应性生存策略，以应对持续的负能量平衡，这种平衡引发了增强的觅食状态。综上所述，这些数据为衰老过程中慢性热量限制有益作用背后的潜在机制提供了新的见解。
