Vitamin C attenuates primate bone marrow aging at the molecular and progenitor level.

Yanxia Ye, Honghao Zhang, Zijuan Xin, Wanling Sun, Lixiao Liu, Muzhao Xiong, Hongkai Zhao, Yiyuan Zhang, Jiaqi Geng, Liyun Zhao, Jingyi Li, Xiaoyu Jiang, Yuesheng Zuo, Shuai Ma, Hongjia Zhang, Si Wang, Guoguang Zhao, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Guang-Hui Liu

State Key Laboratory of Organ Regeneration and Reconstruction, Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.State Key Laboratory of Organ Regeneration and Reconstruction, Human Organ Physiopathology Emulation System, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China. · pubmed

Paper

Abstract

Bone marrow aging compromises hematopoiesis and immunity, yet whether these processes are modifiable in primates remains unexplored. Here, we map the single-cell transcriptomic landscape of primate bone marrow aging and demonstrate that long-term oral vitamin C (VC) supplementation attenuates selected molecular and progenitor-level decline. Aging drives severe common lymphoid progenitor (CLP) depletion, myeloid-biased hematopoietic stem and progenitor cell (HSPC) output, and anatomical site-specific molecular adaptations. VC administration partially offsets these phenotypes, expanding the CLP pool and rebalancing lineage commitment trajectories. This aligns with a ∼4-year reduction in transcriptomic age estimates, cross-validated by an epigenetic clock. Cell-cell communication analyses revealed that VC remodels intercellular signaling, nominating a VC-responsive, progranulin (GRN)-linked candidate pathway. In parallel, human in vitro assays demonstrate that recombinant progranulin mirrors selected VC-associated molecular actions. Collectively, these findings delineate the molecular architecture of primate bone marrow aging and nominate modifiable pathways for further investigation.

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Research summary

Long-term oral vitamin C supplementation attenuates molecular and progenitor-level decline in primate bone marrow aging, effectively reducing transcriptomic age by approximately four years. This study provides direct evidence in a non-human primate model that a common dietary supplement can modify specific hallmarks of hematopoietic aging, offering a potential low-risk intervention for age-related immune decline.

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