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Mechanisms involved in hematopoietic stem cell aging

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Abstract

Hematopoietic stem cells (HSCs) undergo progressive functional decline over time due to both internal and external stressors, leading to aging of the hematopoietic system. A comprehensive understanding of the molecular mechanisms underlying HSC aging will be valuable in developing novel therapies for HSC rejuvenation and to prevent the onset of several age-associated diseases and hematological malignancies. This review considers the general causes of HSC aging that range from cell-intrinsic factors to cell-extrinsic factors. In particular, epigenetics and inflammation have been implicated in the linkage of HSC aging, clonality, and oncogenesis. The challenges in clarifying mechanisms of HSC aging have accelerated the development of therapeutic interventions to rejuvenate HSCs, the major goal of aging research; these details are also discussed in this review.

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Funding

This work was supported by Grant-in-Aid for Scientific Research (A) (No. 20H00537) (to T.K.), Grant-in-Aid for Scientific Research on Innovative Areas “Stem Cell Aging and Disease” (No. 17H05634), The Tokyo Biochemical Research Foundation (to T.K.), Japanese Society of Hematology (to T.K.).

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  1. Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan

    Takeshi Fujino & Toshio Kitamura

  2. The Institute of Laboratory Animals, Tokyo Women’s Medical University, Tokyo, 1628666, Japan

    Shuhei Asada

  3. Division of Molecular Oncology Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, 1088639, Japan

    Susumu Goyama

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  1. Takeshi Fujino
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The manuscript was written by TF, SA, SG, and TK took part in writing the manuscript. All authors read and approved the final manuscript.

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Fujino, T., Asada, S., Goyama, S. et al. Mechanisms involved in hematopoietic stem cell aging. Cell. Mol. Life Sci. 79, 473 (2022). https://doi.org/10.1007/s00018-022-04356-5

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