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衰老细胞的清除:基于亚端粒-端粒理论的前景

Elimination of Senescent Cells: Prospects According to the Subtelomere-Telomere Theory.

作者信息

Libertini G, Ferrara N, Rengo G, Corbi G

机构信息

Federico II University, Department of Translational Medical Sciences, Naples, 80138, Italy.

出版信息

Biochemistry (Mosc). 2018 Dec;83(12):1477-1488. doi: 10.1134/S0006297918120064.

Abstract

Cell senescence is an artificially reversible condition activated by various factors and characterized by replicative senescence and typical general alteration of cell functions, including extra-cellular secretion. The number of senescent cells increases with age and contributes strongly to the manifestations of aging. For these reasons, research is under way to obtain "senolytic" compounds, defined as drugs that eliminate senescent cells and therefore reduce aging-associated decay, as already shown in some experiments on animal models. This objective is analyzed in the context of the programmed aging paradigm, as described by the mechanisms of the subtelomere-telomere theory. In this regard, positive effects of the elimination of senescent cells and limits of this method are discussed. For comparison, positive effects and limits of telomerase activation are also analyzed, as well of the combined action of the two methods and the possible association of opportune gene modifications. Ethical issues associated with the use of these methods are outlined.

摘要

细胞衰老一种人为可逆的状态,由多种因素激活,其特征为复制性衰老以及细胞功能(包括细胞外分泌)的典型普遍改变。衰老细胞的数量随年龄增长而增加,并在很大程度上导致衰老的表现。基于这些原因,正在开展研究以获得“衰老细胞溶解剂”化合物,即被定义为能够消除衰老细胞从而减少与衰老相关衰退的药物,这已在一些动物模型实验中得到证实。根据端粒-端粒理论的机制,在程序性衰老范式的背景下分析了这一目标。在这方面,讨论了消除衰老细胞的积极作用及其方法的局限性。为作比较,还分析了端粒酶激活的积极作用和局限性,以及这两种方法的联合作用和适当基因修饰的可能关联。概述了与使用这些方法相关的伦理问题。

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