Bogdanov A N, Voloshin S V, Kunevich E O, Mikhaleva M A
Saint-Petersburg State University, 7-9 University embankment, St. Petersburg 199034, Russian Federation, e-mail:
City Hospital № 40, 9 Borisov str., Sestroretsk, St. Petersburg 197701, Russian Federation.
Adv Gerontol. 2024;37(3):266-275.
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.
所有组织中的体细胞突变数量会随着年龄的增长而增加。这一过程在造血干细胞（HSC）中得到了充分研究。一些突变会导致造血干细胞的增殖优势和扩增，从而形成一个优势克隆。克隆性造血在老年人群中很常见。意义未明的克隆性造血（CHIP）在老年人中是一种更为常见的现象，它被定义为克隆血细胞中的体细胞突变，且不存在任何其他血液系统恶性肿瘤。CHIP的发生是血液系统恶性肿瘤、心血管疾病以及总体生存率降低的一个独立危险因素。CHIP常与参与DNA甲基化的DNMT3A和TET2基因的突变相关。基于甲基化的年龄相关变化，已经开发出了表观遗传人体时钟，从而能够检测表观遗传衰老。表观遗传衰老与CHIP的结合与不良健康结果相关。进一步的研究将揭示克隆性造血和CHIP在衰老、患各种疾病以及确定影响克隆诱变潜力的可行性方面的意义。
