Efficacy of ghrelin as a therapeutic approach for age-related physiological changes
Efficacy of ghrelin as a therapeutic approach for age-related physiological changes
复制标题
DOI：
10.1210/en.2007-1650
复制
发表时间：
2008-07-01
期刊：
影响因子：
4.8
通讯作者：
Akamizu, Takashi
中科院分区：
文献类型：
--
作者：
Ariyasu, Hiroyuki;Iwakura, Hiroshi;Akamizu, Takashi
衰老与摄食量减少和生长激素分泌减少有关，分别称为衰老的厌食症和更年期。这些现象背后的机制还没有完全被理解。尽管有许多方法试图改善这些与年龄相关的生理变化，但没有一种方法取得令人满意的结果。Ghrelin是一种由28个氨基酸组成的酰化肽，是生长激素促分泌素受体的内源性配体。Ghrelin刺激动物和人类的生长激素分泌和食物摄取。以前的研究表明，正常体重的老年人的平均血浆Ghrelin浓度低于年轻人。我们推测，服用Ghrelin可能会改善伴随着衰老和躯体更年期厌食症的代谢和生理变化。首先，75wk龄小鼠禁食72h后，皮下注射Ghrelin(360 mg/kg)，每日2次，连续4d，72h后多次给予Ghrelin，以高瘦体质量比增加摄食量，加速体重恢复。50~80周龄小鼠皮下注射Ghrelin(40微克/公斤)，每周2次。长期服用Ghrelin可使衰老小鼠保持低体重、低肥胖状态。这些结果表明，Ghrelin可能是一种治疗与年龄相关的代谢和生理变化的新方法。
Aging is associated with decreases in food intake and GH secretion, termed the anorexia of aging and somatopause, respectively. The mechanisms underlying these phenomena are not fully understood. Although many approaches have attempted to improve these age-related physiological changes, none have achieved satisfactory results. Ghrelin, a 28-amino-acid acylated peptide, was identified as an endogenous ligand for the GH secretagogue receptor. Ghrelin stimulates GH secretion and food intake in animals and humans. Previous studies have demonstrated that the mean plasma concentrations of ghrelin in normal-weight elderly people were lower than those in younger people. We hypothesized that ghrelin administration might improve the metabolic and physiological changes that accompany the anorexia of aging and somatopause. First, 75-wk-old mice fasted for 72 h, after which they resumed feeding with sc administration of ghrelin (360 mu g/kg) twice daily for 4 d. Multiple administrations of ghrelin after a 72-h fast increased food intake and hastened body weight recovery with a high lean body mass ratio. Next, 50-wk-old mice were sc injected with rat ghrelin (40 mu g/kg) twice weekly from 50-80 wk of age. Long-term administration of ghrelin kept aged mice with low body weight and low adiposity. These results suggest that ghrelin might be a novel approach for the therapy of age-related metabolic and physiological changes.