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基于胰岛素/胰岛素样生长因子-1信号通路(IIS)对不同物种寿命的调控。

Insulin/insulin-like growth factor-1 signalling (IIS) based regulation of lifespan across species.

作者信息

Mathew Rebecca, Pal Bhadra Manika, Bhadra Utpal

机构信息

Functional Genomics and Gene Silencing Group, CSIR - Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, India.

Centre for Chemical Biology, CSIR - Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500007, India.

出版信息

Biogerontology. 2017 Feb;18(1):35-53. doi: 10.1007/s10522-016-9670-8. Epub 2017 Jan 18.

Abstract

An organism's well-being is facilitated by numerous molecular and biochemical pathways that ensure homeostasis within cells and tissues. Aging causes a gradual let-down in the maintenance of homeostasis due to various endogenous and environmental challenges, leading to amassing of damages, functional deterioration of different tissues and vulnerability to ailments. Nutrient sensing pathways that maintain glucose homeostasis in body are involved in regulation of aging. Insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) pathway was the first nutrient sensing pathway discovered to affect the aging process. This pathway is highly conserved and the most studied among different organisms. Epigenetic machineries that include DNA and histone modifying enzymes and various non-coding RNAs have been identified as important contributors to nutrition-related longevity and aging control. In this report, we present the homology and differences in IIS pathway of various organisms including worm, fly, rodent and human. We also discuss how epigenome remodelling, chromatin based strategies, small and long non-coding RNA are involved to regulate multiple steps of aging or age-related insulin homeostasis. Enhanced study of the role of IIS pathway and epigenetic mechanisms that regulate aging may facilitate progressive prevention and treatment of human age-related diseases.

摘要

多种分子和生化途径有助于维持生物体的健康,确保细胞和组织内的稳态。由于各种内源性和环境挑战,衰老会导致体内稳态维持能力逐渐下降,进而引发损伤积累、不同组织功能退化以及对疾病的易感性增加。维持体内葡萄糖稳态的营养感应途径参与衰老的调节。胰岛素/胰岛素样生长因子-1(IGF-1)信号通路(IIS)是首个被发现影响衰老过程的营养感应途径。该途径在不同生物中高度保守且研究最多。包括DNA和组蛋白修饰酶以及各种非编码RNA在内的表观遗传机制已被确定为营养相关长寿和衰老控制的重要因素。在本报告中,我们阐述了线虫、果蝇、啮齿动物和人类等不同生物IIS途径的异同。我们还讨论了表观基因组重塑、基于染色质的策略、小非编码RNA和长非编码RNA如何参与调节衰老的多个步骤或与年龄相关的胰岛素稳态。加强对IIS途径和调节衰老的表观遗传机制作用的研究,可能有助于逐步预防和治疗人类与年龄相关的疾病。

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