Aging is associated with increased mutational burden in every tissue studied. Occasionally, fitness-increasing mutations will arise, leading to stem cell clonal expansion. This process occurs in several tissues but has been best studied in blood. Clonal hematopoiesis is associated with an increased risk of blood cancers, such as acute myeloid leukemia, which result if additional cooperating mutations occur. Surprisingly, it is also associated with an increased risk of nonmalignant diseases, such as atherosclerotic cardiovascular disease. This may be due to enhanced inflammation in mutated innate immune cells, which could be targeted clinically with anti-inflammatory drugs. Recent studies have uncovered other factors that predict poor outcomes in patients with clonal hematopoiesis, such as size of the mutant clone, mutated driver genes, and epigenetic aging. Though clonality is inevitable and largely a function of time, recent work has shown that inherited genetic variation can also influence this process. Clonal hematopoiesis provides a paradigm for understanding how age-related changes in tissue stem cell composition and function influence human health.

中文翻译：

---

克隆造血及其对人类健康的影响

衰老与所研究的每个组织中突变负担的增加有关。有时，会出现适应度增加的突变，导致干细胞克隆扩张。这个过程发生在多种组织中，但在血液中得到了最好的研究。克隆造血与血癌风险增加有关，例如急性髓系白血病，如果发生额外的协同突变，就会导致这种情况。令人惊讶的是，它还与动脉粥样硬化性心血管疾病等非恶性疾病的风险增加有关。这可能是由于突变的先天免疫细胞的炎症增强，这可以在临床上用抗炎药物来靶向。最近的研究发现了其他预测克隆性造血患者预后不良的因素，例如突变克隆的大小、突变的驱动基因和表观遗传衰老。尽管克隆性是不可避免的，并且很大程度上是时间的函数，但最近的研究表明，遗传变异也可以影响这一过程。克隆造血为理解组织干细胞组成和功能的年龄相关变化如何影响人类健康提供了范例。