Bartke A, Chandrashekar V, Dominici F, Turyn D, Kinney B, Steger R, Kopchick J J
Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62901-6512, USA.
Biogerontology. 2003;4(1):1-8. doi: 10.1023/a:1022448532248.
Insulin/insulin-like growth factor (IGF) signaling plays a major role in the control of aging and life span in invertebrates. Major extension of life span in growth hormone receptor knock out (GHR-KO) mice that are GH resistant, and subsequently, IGF-I-deficient indicates that similar mechanisms may operate in mammals. This conclusion is supported by association of reduced IGF-I levels and delayed aging in three different GH-deficient mutant mice and in animals subjected to caloric restriction, but is difficult to reconcile with neuroprotective effects of IGF-I and with the suspected role of declining GH levels during aging. We suggest that the role of IGF in the regulation of growth and adult body size is important in mediating the effects of longevity genes on aging and life span. Suspected mechanisms of IGF-I action in aging also include reduced insulin signaling, enhanced sensitivity to insulin, and reduced thermogenesis with diminished oxidative damage of macromolecules being the likely final common pathway of these effects. We suspect that IGF-I is important in evolutionarily conserved mechanisms that link life history, including development, reproduction, and aging with availability of energy resources.
胰岛素/胰岛素样生长因子（IGF）信号传导在无脊椎动物衰老和寿命控制中起主要作用。生长激素受体敲除（GHR-KO）小鼠（即对生长激素有抗性，随后缺乏IGF-I）的寿命显著延长，这表明类似机制可能在哺乳动物中起作用。这一结论得到了三种不同的生长激素缺乏突变小鼠以及热量限制动物中IGF-I水平降低与衰老延迟之间关联的支持，但难以与IGF-I的神经保护作用以及衰老过程中生长激素水平下降的推测作用相协调。我们认为，IGF在调节生长和成年体型方面的作用对于介导长寿基因对衰老和寿命的影响很重要。IGF-I在衰老过程中作用的推测机制还包括胰岛素信号传导减少、对胰岛素的敏感性增强以及产热减少，而大分子氧化损伤减少可能是这些作用的最终共同途径。我们怀疑IGF-I在将包括发育、繁殖和衰老在内的生命历程与能量资源可用性联系起来的进化保守机制中很重要。
