衰老的特征在共济失调毛细血管扩张症。

The hallmarks of aging in Ataxia-Telangiectasia.

机构信息

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Queensland 4072, Australia.

出版信息

Ageing Res Rev. 2022 Aug;79:101653. doi: 10.1016/j.arr.2022.101653. Epub 2022 May 26.

DOI:10.1016/j.arr.2022.101653

Abstract

Ataxia-telangiectasia (A-T) is caused by absence of the catalytic activity of ATM, a protein kinase that plays a central role in the DNA damage response, many branches of cellular metabolism, redox and mitochondrial homeostasis, and cell cycle regulation. A-T is a complex disorder characterized mainly by progressive cerebellar degeneration, immunodeficiency, radiation sensitivity, genome instability, and predisposition to cancer. It is increasingly recognized that the premature aging component of A-T is an important driver of this disease, and A-T is therefore an attractive model to study the aging process. This review outlines the current state of knowledge pertaining to the molecular and cellular signatures of aging in A-T and proposes how these new insights can guide novel therapeutic approaches for A-T.

摘要

共济失调毛细血管扩张症（A-T）是由 ATM 缺乏催化活性引起的，ATM 是一种蛋白激酶，在 DNA 损伤反应、细胞代谢的许多分支、氧化还原和线粒体稳态以及细胞周期调控中发挥核心作用。A-T 是一种复杂的疾病，主要表现为进行性小脑变性、免疫缺陷、辐射敏感性、基因组不稳定性和易患癌症。人们越来越认识到，A-T 的过早衰老成分是该疾病的重要驱动因素，因此 A-T 是研究衰老过程的一个有吸引力的模型。这篇综述概述了与 A-T 衰老的分子和细胞特征相关的现有知识，并提出了这些新的见解如何为 A-T 的新治疗方法提供指导。