Clonal hematopoiesis of indeterminate potential (CHIP), defined as the presence of somatic mutations in cancer-related genes in blood cells in the absence of hematological cancer, has recently emerged as an important risk factor for several age-related conditions, especially cardiovascular disease. CHIP is strongly associated with normal aging, but its role in premature aging syndromes is unknown. Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare genetic condition driven by the accumulation of a truncated form of the lamin A protein called progerin. HGPS patients exhibit several features of accelerated aging and typically die from cardiovascular complications in their early teens. Previous studies have shown normal hematological parameters in HGPS patients, except for elevated platelets, and low levels of lamin A expression in hematopoietic cells relative to other cell types in solid tissues, but the prevalence of CHIP in HGPS remains unexplored. To investigate the potential role of CHIP in HGPS, we performed high-sensitivity targeted sequencing of CHIP-related genes in blood DNA samples from a cohort of 47 HGPS patients. As a control, the same sequencing strategy was applied to blood DNA samples from middle-aged and elderly individuals, expected to exhibit a biological age and cardiovascular risk profile similar to HGPS patients. We found that CHIP is not prevalent in HGPS patients, in marked contrast to our observations in individuals who age normally. Thus, our study unveils a major difference between HGPS and normal aging and provides conclusive evidence that CHIP is not frequent in HGPS and, therefore, is unlikely to contribute to the pathophysiology of this accelerated aging syndrome.

不确定潜能的克隆性造血 (CHIP) 定义为在没有血液癌症的情况下血细胞中癌症相关基因存在体细胞突变，最近已成为几种与年龄相关的疾病，尤其是心血管疾病的重要危险因素。CHIP 与正常衰老密切相关，但其在过早衰老综合征中的作用尚不清楚。Hutchinson-Gilford 早衰综合症 (HGPS) 是一种极为罕见的遗传病，由称为早衰蛋白的核纤层蛋白 A 的截短形式的积累驱动。HGPS 患者表现出加速衰老的几个特征，并且通常在他们十几岁的时候死于心血管并发症。先前的研究表明 HGPS 患者的血液学参数正常，血小板升高除外，和造血细胞中核纤层蛋白 A 表达水平相对于实体组织中其他细胞类型的低水平，但 CHIP 在 HGPS 中的普遍性仍未得到探索。为了研究 CHIP 在 HGPS 中的潜在作用，我们对来自 47 名 HGPS 患者的血液 DNA 样本中的 CHIP 相关基因进行了高灵敏度靶向测序。作为对照，将相同的测序策略应用于中年和老年人的血液 DNA 样本，预计这些样本具有与 HGPS 患者相似的生物学年龄和心血管风险特征。我们发现 CHIP 在 HGPS 患者中并不普遍，这与我们在正常年龄的个体中的观察结果形成鲜明对比。因此，我们的研究揭示了 HGPS 与正常衰老之间的主要差异，并提供了确凿的证据表明 CHIP 在 HGPS 中并不常见，因此，