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DNA重组与生物衰老。综述。

DNA reorganization and biological aging. A review.

作者信息

Osiewacz H D, Hamann A

机构信息

Botanisches Institut, Molekulare Entwicklungsbiologie und Biotechnologie, Johann Wolfgang Goethe-Universität, Frankfurt/Main, Germany.

出版信息

Biochemistry (Mosc). 1997 Nov;62(11):1275-84.

PMID:9467851
Abstract

Biological aging is a fundamental process observed in almost all living beings. It is characterized by a progressive impairment of biological systems leading to an increase in age-related mortality. The understanding of the mechanisms of aging is of particular interest not only from a general point of view, but it has wide implications for both the human individual and society. Specifically, understanding the basic mechanisms leading to human aging will certainly provide novel strategies to deal with the many different and severe age-related diseases (e.g., different types of cancer, Alzheimer's disease, cardiovascular diseases) and can be expected to increase the quality of life in old age significantly. Despite this obvious significance, it is amazing how little is known about the basis of aging. Currently, it is not clear whether there exists a single conserved mechanism by which all biological systems age, nor is it clear whether or not such a mechanism accounts for aging in a single species. However, beside these and many other open issues, it is clear today that there is a genetic component of aging. It is also clear that age-dependent changes of genetic information play an important role. The processes leading to the observed age-related accumulation of DNA alterations is dependent on two major factors: the rate at which the alterations occur and the ability of the biological system to repair them. In addition, there are a number of different types of DNA alterations known. One group of changes are unspecific and occur randomly. Other alterations result from the differential activity of specific genetic traits (e.g., age-related genes, mobile genetic elements). Moreover, DNA changes may be subtle, occurring at the nucleotide level, or may include larger regions of the genetic information. In this review we focus on the latter type of age-related DNA reorganizations. We will refer to reorganizations which are of special relevance in different biological systems.

摘要

生物衰老几乎是所有生物都存在的一个基本过程。其特征是生物系统逐渐受损,导致与年龄相关的死亡率上升。对衰老机制的理解不仅从一般角度来看特别有趣,而且对人类个体和社会都有广泛影响。具体而言,了解导致人类衰老的基本机制肯定会提供新的策略来应对许多不同且严重的与年龄相关的疾病(例如,不同类型的癌症、阿尔茨海默病、心血管疾病),并有望显著提高老年人的生活质量。尽管具有如此明显的重要性,但令人惊讶的是,我们对衰老的基础知之甚少。目前,尚不清楚是否存在一种所有生物系统都通过其衰老的单一保守机制,也不清楚这样一种机制是否能解释单一物种的衰老。然而,除了这些以及许多其他未解决的问题之外,如今很明显衰老存在遗传成分。同样明显的是,遗传信息的年龄依赖性变化起着重要作用。导致观察到的与年龄相关的DNA改变积累的过程取决于两个主要因素:改变发生的速率以及生物系统修复它们的能力。此外,已知有许多不同类型的DNA改变。一类变化是非特异性的,随机发生。其他改变则源于特定遗传特征(例如,与年龄相关的基因、移动遗传元件)的差异活性。而且,DNA变化可能很细微,发生在核苷酸水平,或者可能包括遗传信息的更大区域。在这篇综述中,我们关注后一种与年龄相关的DNA重组类型。我们将提及在不同生物系统中具有特殊相关性的重组。

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