The impact of age and number of mutations on the size of clonal hematopoiesis.

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

Citation

Kai Wang, Wen Zhang, Li Yi, Ming Zhao, Peng-Yu Li, Mei-Hong Fu, Rong Lin, Yong-Mei Zhu, Jian-Feng Li, Wei-Ping Yang, Hai Fang, Zhu Chen, Wang-Wei Cai, Rui-Bao Ren. The impact of age and number of mutations on the size of clonal hematopoiesis. Proceedings of the National Academy of Sciences of the United States of America. 2024 Feb 20;121(8):e2319364121

Mesh Tags

Substances

PMID: 38359296

search → result