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营养表观遗传学。

Nutritional epigenetics.

作者信息

Niculescu Mihai D

机构信息

Nutrition Research Institute and Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, North Carolina 28081, USA.

出版信息

ILAR J. 2012;53(3-4):270-8. doi: 10.1093/ilar.53.3-4.270.

Abstract

Within the last two decades, significant progress has been made in understanding the importance of epigenetic mechanisms in the regulation of gene expression as a consequence of gene-environment interactions. Nutrition, among many other environmental factors, is a key player that can induce epigenetic changes not only in the directly exposed organisms but also in subsequent generations through the transgenerational inheritance of epigenetic traits. This article aims to provide insights into the usefulness of the mouse model for epigenetic studies involving nutrition as well as the inherent limitations when compared with epigenetic phenomena in humans. Mice are one of the most versatile models for nutrition and epigenetic studies because of several features, such as short life-span, relative low cost for generating samples, the existence of well-characterized genetically engineered lines, the detailed sequencing of genomes, and the relative similarity of their metabolic processes to human metabolism. However, several limitations have to be acknowledged, such as the different location of genes on the chromosomes (and hence possibly different consequences of some epigenetic alterations), differences in the epigenetic patterns established during late embryogenesis, and possible epigenetic differences associated with cellular senescence caused by the different structure of telomeres when compared with humans. All these aspects have to be carefully analyzed when deciding whether a mouse model should be considered for a study in nutrition and epigenetics. Consequently, the results obtained from mouse studies should be carefully interpreted regarding their relevance to humans.

摘要

在过去二十年中,由于基因与环境的相互作用,人们在理解表观遗传机制在基因表达调控中的重要性方面取得了重大进展。在众多环境因素中,营养是一个关键因素,它不仅可以在直接暴露的生物体中诱导表观遗传变化,还可以通过表观遗传特征的跨代遗传在后代中诱导这种变化。本文旨在深入探讨小鼠模型在涉及营养的表观遗传研究中的实用性,以及与人类表观遗传现象相比所固有的局限性。由于寿命短、生成样本的成本相对较低、存在特征明确的基因工程品系、基因组的详细测序以及其代谢过程与人类代谢的相对相似性等多种特征,小鼠是营养和表观遗传研究中最通用的模型之一。然而,必须承认一些局限性,例如基因在染色体上的位置不同(因此某些表观遗传改变可能产生不同的后果)、胚胎后期发育过程中建立的表观遗传模式的差异,以及与人类相比,由于端粒结构不同导致的细胞衰老相关的可能表观遗传差异。在决定是否应考虑使用小鼠模型进行营养和表观遗传学研究时,所有这些方面都必须仔细分析。因此,从小鼠研究中获得的结果应根据其与人类的相关性进行仔细解读。

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