Centro de Biología Molecular, Severo Ochoa (UAM-CSIC), Universidad Autónoma, 28049 Madrid, Spain.
Curr Protein Pept Sci. 2011 Jun;12(4):305-15. doi: 10.2174/138920311795906655.
Aging in mammals associates with the development of peripheral insulin resistance. Additionally, adiposity usually increases with aging and this could play a relevant role in the gradual impairment of insulin action. In fact, fat accretion leads to changes in the expression and circulating concentrations of factors originated in adipose tissue like leptin, resistin and inflammatory cytokines which have been shown to modulate insulin signaling in insulin target tissues acting both, directly or through the central nervous system. Even insulin action on peripheral target tissues has been recently demonstrated to be partially mediated by its central action, suggesting that a decrease in central insulin action could be involved in the development of peripheral insulin resistance. In the present review we analyze the available research data on aging-associated insulin resistance making emphasis in the following aspects: 1) The time-course of development of overall insulin resistance and the evolution of changes in circulating adipokines; 2) The effect of caloric restriction and the decrease of adiposity in insulin action; 3) The influence of changes in the central action of factors like leptin or insulin in the development and maintenance of insulin resistance during aging.
哺乳动物的衰老与外周胰岛素抵抗的发展有关。此外，肥胖通常随着年龄的增长而增加，这可能在胰岛素作用的逐渐受损中发挥相关作用。事实上，脂肪堆积导致来源于脂肪组织的如瘦素、抵抗素和炎性细胞因子等因子的表达和循环浓度发生变化，这些因子已被证明可调节胰岛素靶组织中的胰岛素信号，直接或通过中枢神经系统发挥作用。甚至胰岛素对周围靶组织的作用也被最近证明部分由其中枢作用介导，这表明中枢胰岛素作用的降低可能与外周胰岛素抵抗的发展有关。在本综述中，我们分析了与衰老相关的胰岛素抵抗的现有研究数据，重点关注以下几个方面：1）整体胰岛素抵抗的发展时间过程和循环脂肪因子变化的演变；2）热量限制和肥胖减少对胰岛素作用的影响；3）瘦素或胰岛素等因子的中枢作用变化对衰老过程中胰岛素抵抗的发展和维持的影响。
