Age-related alterations in the human blood system occur in B cells, T cells, cells of the innate system, as well as hematopoietic stem and progenitor cells (HSPCs). Interestingly, age-related, reduced genetic diversity can be identified at the stem cell level and also independently in B cells and T cells. This reduced diversity is most probably related to somatic mutations or to changes in the microenvironmental niche. Either process can select for specific clones or cause repeated evolutionary bottlenecks. This review discusses the age-related clonal expansions in the human HSPC pool, which was termed in the past age-related clonal hematopoiesis (ARCH). ARCH is defined as the gradual, clonal expansion of HSPCs carrying specific, disruptive, and recurrent genetic variants, in individuals without clear diagnosis of hematological malignancies. ARCH is associated not just with chronological aging but also with several other, age-related pathological conditions, including inflammation, vascular diseases, cancer mortality, and high risk for hematological malignancies. Although it remains unclear whether ARCH is a marker of aging or plays an active role in these various pathophysiologies, it is suggested here that treating or even preventing ARCH may prove to be beneficial for human health. This review also describes a decision tree for the diagnosis and follow-up for ARCH in a research setting.

中文翻译：

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年龄相关的克隆性造血 (ARCH)

人类血液系统中与年龄相关的改变发生在 B 细胞、T 细胞、先天系统细胞以及造血干细胞和祖细胞 (HSPC) 中。有趣的是，可以在干细胞水平上以及在 B 细胞和 T 细胞中独立地识别出与年龄相关的遗传多样性降低。这种减少的多样性很可能与体细胞突变或微环境生态位的变化有关。任何一个过程都可以选择特定的克隆或导致重复的进化瓶颈。本综述讨论了人类 HSPC 库中与年龄相关的克隆扩增，这在过去的年龄相关克隆造血 (ARCH) 中被称为。ARCH 被定义为携带特定的、破坏性的和复发性遗传变异的 HSPC 在没有明确的血液系统恶性肿瘤诊断的个体中的逐渐克隆扩增。ARCH 不仅与时间老化有关，还与其他几种与年龄相关的病理状况有关，包括炎症、血管疾病、癌症死亡率和血液系统恶性肿瘤的高风险。虽然尚不清楚 ARCH 是否是衰老的标志或在这些各种病理生理学中起积极作用，但这里建议治疗甚至预防 ARCH 可能证明对人类健康有益。本综述还描述了研究环境中 ARCH 诊断和随访的决策树。虽然尚不清楚 ARCH 是否是衰老的标志或在这些各种病理生理学中起积极作用，但这里建议治疗甚至预防 ARCH 可能证明对人类健康有益。本综述还描述了研究环境中 ARCH 诊断和随访的决策树。虽然尚不清楚 ARCH 是否是衰老的标志或在这些各种病理生理学中起积极作用，但这里建议治疗甚至预防 ARCH 可能证明对人类健康有益。本综述还描述了研究环境中 ARCH 诊断和随访的决策树。