Totani Haruhito, Matsumura Takayoshi, Yokomori Rui, Umemoto Terumasa, Takihara Yuji, Yang Chong, Chua Lee Hui, Watanabe Atsushi, Sanda Takaomi, Suda Toshio
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Division of Cardiovascular and Genetic Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
Nat Aging. 2025 May;5(5):831-847. doi: 10.1038/s43587-025-00828-y. Epub 2025 Mar 6.
The aging of hematopoietic stem cells (HSCs) substantially alters their characteristics. Mitochondria, essential for cellular metabolism, play a crucial role, and their dysfunction is a hallmark of aging-induced changes. The impact of mitochondrial mass on aged HSCs remains incompletely understood. Here we demonstrate that HSCs with high mitochondrial mass during aging are not merely cells that have accumulated damaged mitochondria and become exhausted. In addition, these HSCs retain a high regenerative capacity and remain in the aging bone marrow. Furthermore, we identified GPR183 as a distinct marker characterizing aged HSCs through single-cell analysis. HSCs marked by GPR183 were also enriched in aged HSCs with high mitochondrial mass, possessing a high capacity of self-renewal. These insights deepen understanding of HSC aging and provide additional perspectives on the assessment of aged HSCs, underscoring the importance of mitochondrial dynamics in aging.
造血干细胞（HSCs）的衰老显著改变了它们的特性。线粒体是细胞代谢所必需的，发挥着关键作用，其功能障碍是衰老诱导变化的一个标志。线粒体质量对衰老造血干细胞的影响仍未完全了解。在这里，我们证明衰老过程中线粒体质量高的造血干细胞不仅仅是积累了受损线粒体并变得耗竭的细胞。此外，这些造血干细胞保留了高再生能力，并存在于衰老的骨髓中。此外，我们通过单细胞分析确定GPR183是表征衰老造血干细胞的一个独特标志物。以GPR183标记的造血干细胞在具有高线粒体质量的衰老造血干细胞中也很丰富，具有高自我更新能力。这些见解加深了对造血干细胞衰老的理解，并为评估衰老造血干细胞提供了更多视角，强调了线粒体动力学在衰老中的重要性。
