早期成长和衰老。

J-H Chen, E C Cottrell, S E Ozanne
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引用次数: 14

摘要

宫内和早期生活状况对成人健康和心血管疾病和2型糖尿病等疾病的影响已被流行病学和临床观察充分记录。包括宫内动脉结扎、母体限制铁、蛋白质或一般热量摄入在内的动物模型,为了解早期生长与成年后疾病之间的联系机制提供了宝贵的工具。此外,母体蛋白质限制的啮齿动物模型表明,早期生长模式可能对寿命产生积极或消极的影响。最近在衰老领域的快速进展使用模式生物涉及热量限制和基因突变以及基因过表达证明了胰岛素/ IGF-1信号通路,氧化损伤和SIRT1在调节寿命中的重要性。利用母体蛋白限制的啮齿动物模型进行的研究表明,胰岛素代谢的改变、抗氧化防御系统表达的改变和氧化损伤水平(包括端粒磨损)也可能在早期环境对寿命的调节中发挥关键作用。提示神经内分泌系统和表观遗传修饰可能是早期生长对寿命调控有利或有害的潜在机制。这方面的进一步研究是有必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Early growth and ageing.

Effects of in utero and early life conditions on adult health and disease such as cardiovascular disease and type 2 diabetes are well documented by epidemiological and clinical observations. Animal models including intrauterine artery ligation, maternal restriction of iron, protein or general caloric intake, provide invaluable tools to understand mechanisms linking early growth and later diseases in adult life. In addition, the rodent model of maternal protein restriction has revealed that longevity can be influenced either positively or negatively by early growth patterns. Recent rapid advances in the ageing field using model organisms involving caloric restriction and genetic mutation as well as gene overexpression demonstrated the importance of insulin/ IGF-1 signaling pathways, oxidative damage and SIRT1 in the regulation of lifespan. Studies using rodent models of maternal protein restriction suggest that alteration in insulin metabolism, changes in expression of antioxidant defense systems and in levels of oxidative damage (including telomere attrition) may also play a key role in regulation of lifespan by the early environment. It is suggested that neuroendocrine systems and epigenetic modification may be the potential mechanisms underlying beneficial or detrimental effects of early growth on the regulation of lifespan. Further studies in this area are warranted.

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