State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Cell Stem Cell. 2023 Dec 7;30(12):1674-1691.e8. doi: 10.1016/j.stem.2023.09.014. Epub 2023 Oct 27.
Regeneration across tissues and organs exhibits significant variation throughout the body and undergoes a progressive decline with age. To decode the relationships between aging and regenerative capacity, we conducted a comprehensive single-cell transcriptome analysis of regeneration in eight tissues from young and aged mice. We employed diverse analytical models to study tissue regeneration and unveiled the intricate cellular and molecular mechanisms underlying the attenuated regenerative processes observed in aged tissues. Specifically, we identified compromised stem cell mobility and inadequate angiogenesis as prominent contributors to this age-associated decline in regenerative capacity. Moreover, we discovered a unique subset of Arg1 macrophages that were activated in young tissues but suppressed in aged regenerating tissues, suggesting their important role in age-related immune response disparities during regeneration. This study provides a comprehensive single-cell resource for identifying potential targets for interventions aimed at enhancing regenerative outcomes in the aging population.
组织和器官的再生能力在全身范围内存在显著差异，并随着年龄的增长逐渐下降。为了解码衰老和再生能力之间的关系，我们对年轻和老年小鼠的 8 种组织的再生进行了全面的单细胞转录组分析。我们采用了多种分析模型来研究组织再生，并揭示了在老年组织中观察到的再生过程减弱的复杂细胞和分子机制。具体而言，我们发现受损的干细胞迁移能力和不足的血管生成是导致这种与年龄相关的再生能力下降的主要因素。此外，我们发现了一组独特的 Arg1 巨噬细胞亚群，它们在年轻组织中被激活，但在老年再生组织中受到抑制，这表明它们在再生过程中对年龄相关的免疫反应差异具有重要作用。这项研究为确定旨在提高老年人群再生效果的干预措施的潜在靶点提供了一个全面的单细胞资源。
