Arai Yasumichi, Kojima Toshio, Takayama Michiyo, Hirose Nobuyoshi
Department of Internal Medicine, Division of Geriatric Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjukuku, Tokyo 160-8582, Japan.
Mol Cell Endocrinol. 2009 Feb 5;299(1):124-8. doi: 10.1016/j.mce.2008.07.002. Epub 2008 Jul 11.
Recent studies have shown that insulin and insulin-like growth factor (IGF)-1 signaling are involved in the control of ageing and longevity in model organisms. Based on these studies, genes involved in the insulin/IGF-1 signaling pathway are believed to play a role in longevity throughout evolution and could also be important in determining human longevity. However, human studies have yielded conflicting and controversial results. In human, defects in insulin receptor signaling cause insulin resistance and diabetes, and IGF-1 deficiency is associated with an increased risk of cardiovascular disease and atherosclerosis. Interestingly, insulin sensitivity normally decreases during aging; however, centenarians were reported to maintain greatly increased insulin sensitivity and had a lower prevalence of the metabolic syndrome as compared to younger subjects. Additionally, a longitudinal study revealed that insulin-sensitizing hormones, including leptin and adiponectin, were significantly associated with the survival of centenarians, indicating that an efficient insulin response may influence human longevity.
最近的研究表明,胰岛素和胰岛素样生长因子(IGF)-1信号通路参与了模式生物衰老和寿命的调控。基于这些研究,参与胰岛素/IGF-1信号通路的基因被认为在整个进化过程中对寿命起着作用,并且在决定人类寿命方面也可能很重要。然而,人体研究得出了相互矛盾且有争议的结果。在人类中,胰岛素受体信号缺陷会导致胰岛素抵抗和糖尿病,而IGF-1缺乏与心血管疾病和动脉粥样硬化风险增加有关。有趣的是,胰岛素敏感性通常在衰老过程中降低;然而,据报道,与年轻受试者相比,百岁老人保持着显著提高的胰岛素敏感性,且代谢综合征的患病率较低。此外,一项纵向研究表明,包括瘦素和脂联素在内的胰岛素增敏激素与百岁老人的生存显著相关,这表明有效的胰岛素反应可能会影响人类寿命。