[衰老与克隆造血]

Q4 Medicine
A N Bogdanov, S V Voloshin, E O Kunevich, M A Mikhaleva
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引用次数: 0

摘要

所有组织中的体细胞突变数量都会随着年龄的增长而增加。造血干细胞对这一过程进行了深入研究。一些突变导致造血干细胞增殖优势和扩增,形成优势克隆。克隆性造血在老年人群中很普遍。具有不确定潜能的克隆性造血(CHIP)在老年人中更为常见,它被定义为克隆血细胞中的体细胞突变,但不伴有任何其他血液恶性肿瘤。CHIP是血液恶性肿瘤、心血管疾病和总生存率降低的独立危险因素。CHIP 常与参与 DNA 甲基化的 DNMT3A 和 TET2 基因突变有关。根据与年龄相关的甲基化变化,人们开发出了表观遗传人体时钟,从而使检测表观遗传衰老成为可能。表观遗传老化与 CHUP 的结合与不良健康后果有关。进一步的研究将揭示克隆造血和 CHIP 在衰老、获得各种疾病以及确定影响克隆突变潜能的可行性方面的意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Aging and clonal hematopoesis.]

The number of somatic mutations among all tissues increases along with age. This process was well-studied in hematopoietic stem cells (HSCs). Some mutations lead to a proliferative advantage and expansion of HSCs to form a dominant clone. Clonal hematopoiesis is general in the elderly population. Clonal hematopoiesis of indeterminate potential (CHIP) is a more common phenomenon in the elderly and is defined as somatic mutations in clonal blood cells without any other hematological malignancies. The development of CHIP is an independent risk factor for hematological malignancies, cardiovascular diseases, and reduced overall survival. CHIP is frequently associated with mutations in DNMT3A and TET2 genes involved in DNA methylation. The epigenetic human body clocks have been developed based on the age-related changes in methylation, making it possible to detect epigenetic aging. The combination of epigenetic aging and CHUP is associated with adverse health outcomes. Further research will reveal the significance of clonal hematopoiesis and CHIP in aging, acquiring various diseases, and determining the feasibility of influencing the mutagenic potential of clones.

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