DiStefano Peter S, Curtis Rory, Geddes Bradley J
Elixir Pharmaceuticals, Inc., 12 Emily Street, Cambridge, MA 02139, USA.
Curr Alzheimer Res. 2007 Apr;4(2):153-7. doi: 10.2174/156720507780362038.
Identification of genes and pathways that alter lifespan has allowed for new insights into factors that control the aging process as well as disease. While strong molecular links exist between aging and metabolism, we hypothesize that targeting the mechanisms involved in aging will also give rise to therapeutics that treat other devastating age-related diseases, such as neurodegeneration, cancer, inflammation and cardiovascular disease. Insulin sensitivity, glycemic control and adiposity are not only hallmarks of the major metabolic diseases, type 2 diabetes and obesity, but they also represent significant risk factors for the development of Alzheimer's Disease and cognitive impairment. Insulin/IGF-1 signaling is an important pathway regulating aging and disease in a variety of species, including mammals. Here we describe an important role for the gut-derived peptide ghrelin in upstream signaling through the insulin/IGF-1 pathway and exemplify modulation of ghrelin signaling as an approach to mechanistic treatment of multiple age-related diseases by virtue of its ability to regulate key metabolic functions.
对影响寿命的基因和通路的识别，为深入了解控制衰老过程以及疾病的因素提供了新的视角。虽然衰老与新陈代谢之间存在着强大的分子联系，但我们推测，针对衰老相关机制的研究也将催生治疗其他严重的年龄相关疾病的疗法，如神经退行性疾病、癌症、炎症和心血管疾病。胰岛素敏感性、血糖控制和肥胖不仅是主要代谢疾病（2型糖尿病和肥胖症）的标志，也是阿尔茨海默病和认知障碍发展的重要危险因素。胰岛素/胰岛素样生长因子-1信号通路是调节包括哺乳动物在内的多种物种衰老和疾病的重要途径。在此，我们描述了肠道来源的肽胃饥饿素在通过胰岛素/胰岛素样生长因子-1通路的上游信号传导中的重要作用，并举例说明了调节胃饥饿素信号传导作为一种机制性治疗多种年龄相关疾病的方法，因为它具有调节关键代谢功能的能力。
