Barbieri Michelangela, Bonafè Massimiliano, Franceschi Claudio, Paolisso Giuseppe
Department of Geriatric Medicine and Metabolic Diseases, University of Naples, 80138 Naples, Italy.
Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E1064-71. doi: 10.1152/ajpendo.00296.2003.
Although the underlying mechanisms of longevity are not fully understood, it is known that mutation in genes that share similarities with those in humans involved in the insulin/insulin-like growth factor I (IGF-I) signal response pathway can significantly extend life span in diverse species, including yeast, worms, fruit flies, and rodents. Intriguingly, the long-lived mutants, ranging from yeast to mice, share some important phenotypic characteristics, including reduced insulin signaling, enhanced sensitivity to insulin, and reduced IGF-I plasma levels. Such genetic homologies and phenotypic similarities between insulin/IGF-I pathway mutants raise the possibility that the fundamental mechanism of aging may be evolutionarily conserved from yeast to mammals. Very recent findings also provide novel and intriguing evidence for the involvement of insulin and IGF-I in the control of aging and longevity in humans. In this study, we focus on how the insulin/IGF-I pathway controls yeast, nematode, fruit fly, and rodent life spans and how it is related to the aging process in humans to outline the prospect of a unifying mechanism in the genetics of longevity.
尽管长寿的潜在机制尚未完全明确，但已知与参与胰岛素/胰岛素样生长因子I（IGF-I）信号反应途径的人类基因具有相似性的基因突变，能够显著延长包括酵母、线虫、果蝇和啮齿动物在内的多种物种的寿命。有趣的是，从酵母到小鼠的长寿突变体具有一些重要的表型特征，包括胰岛素信号传导减弱、对胰岛素的敏感性增强以及血浆IGF-I水平降低。胰岛素/IGF-I途径突变体之间的这种基因同源性和表型相似性，增加了衰老的基本机制可能在从酵母到哺乳动物的进化过程中保持保守的可能性。最近的研究结果也为胰岛素和IGF-I参与人类衰老和长寿的控制提供了新颖且有趣的证据。在本研究中，我们关注胰岛素/IGF-I途径如何控制酵母、线虫、果蝇和啮齿动物的寿命，以及它与人类衰老过程的关系，以概述长寿遗传学中统一机制的前景。
