As we age, the bone marrow gradually loses its rhythm. This hidden factory for blood and immune cells produces fewer essential components over time. More defective parts emerge, and the quality control team shrinks. Hematopoietic stem cells increasingly favor the myeloid lineage over lymphoid production, tilting the immune system's balance. Older bodies become vulnerable to infections, weak vaccine responses, and blood cancers. For years, scientists debated whether this decline was an irreversible fate. Now a new study in non-human primates shows that a simple daily nutrient, vitamin C, can turn back the clock.

Beijing, July 16, 2026 – In a study published today in Cell Stem Cell, researchers from the Chinese Academy of Sciences, Capital Medical University, and international partners report that long-term oral vitamin C supplementation attenuates age-related deterioration of bone marrow at both the cellular and molecular levels. Using a 40-month longitudinal intervention in aged cynomolgus macaques, a model closely mirroring human physiology, the team demonstrated that vitamin C not only corrects lineage imbalances in hematopoietic progenitors but also reduces transcriptomic and epigenetic age estimates by an average of 3 to 4 years.

The experiment involved aged female monkeys, equivalent to 40 to 53 human years, receiving a daily oral dose of 30 mg/kg vitamin C. Young and middle-aged animals served as controls. Bone marrow from two anatomically distinct sites, the rib and femur, was subjected to deep single-cell RNA sequencing, complemented by DNA methylation profiling. To quantify aging, the researchers built a primate-specific single-cell transcriptomic clock and a separate epigenetic clock, both trained on untreated animals.

Aging consistently depleted common lymphoid progenitors (CLPs), the precursors of lymphocytes. At the same time, aging skewed hematopoietic stem cells toward myeloid differentiation. Vitamin C partially reversed these shifts. CLP frequencies increased, and the lymphoid-to-myeloid ratio moved closer to that of young animals.

Notably, the transcriptomic clock estimated that vitamin C-treated bone marrow cells appeared 4.07 years younger on average. Immature B cells showed up to 9.35 years of rejuvenation in the rib. An independent DNA methylation clock confirmed this trend, showing a similar 3.44-year reduction in epigenetic age.

Mechanistically, the study pinpointed the progranulin signaling axis as a key mediator. Progranulin is a homeostatic growth factor that declines with age. Its levels were elevated in vitamin C-treated animals, and its intercellular communication networks were partially restored. In parallel human in vitro experiments, recombinant progranulin mimicked several of vitamin C's protective effects on old hematopoietic stem cells and T cells. These effects included reduction of oxidative damage and restoration of nuclear lamina proteins, suggesting that the vitamin C-progranulin pathway may be a conserved regulatory module.

Notably, the effects were observed across both skeletal sites, though with some site-specific nuances. The femur showed a slightly larger reduction in predicted age than the rib, highlighting how local microenvironments interact with systemic interventions. This work provides an openly accessible single-cell atlas of primate bone marrow aging and a framework for evaluating interventions. The identification of a vitamin C-responsive, progranulin-linked pathway opens new avenues for maintaining immune resilience in the growing elderly population. Further translational studies will be needed to bridge the gap to clinical application.

DOI: https://doi.org/10.1016/j.stem.2026.06.006

Contact

LIU Guang-Hui

Institute of Zoology, Chinese Academy of Sciences

Tel: +86-10-64807583

E-mail: ghliu@ioz.ac.cn

Web: http://english.ioz.cas.cn/

Vitamin C Restores Heterochromatin State in Aged Monkey’s Bone Marrow: Aged control rib bone marrow cells (left) show reduced H3K9me3 (yellow); rib bone marrow cells from vitamin C-treated aged monkeys (right) exhibit partial restoration of this histone mark. (Image by LIU Guang-Hui's lab)