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Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a

Author

Listed:
  • Viktor Janzen

    (Massachusetts General Hospital, Harvard Medical School
    Harvard University
    University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute)

  • Randolf Forkert

    (Massachusetts General Hospital, Harvard Medical School
    Harvard University
    University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute)

  • Heather E. Fleming

    (Massachusetts General Hospital, Harvard Medical School
    Harvard University)

  • Yoriko Saito

    (Massachusetts General Hospital, Harvard Medical School
    Harvard University)

  • Michael T. Waring

    (Massachusetts General Hospital, Harvard Medical School)

  • David M. Dombkowski

    (Massachusetts General Hospital, Harvard Medical School)

  • Tao Cheng

    (Massachusetts General Hospital, Harvard Medical School)

  • Ronald A. DePinho

    (Dana-Farber Cancer Institute, Departments of Medicine and Genetics, Harvard Medical School)

  • Norman E. Sharpless

    (The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine)

  • David T. Scadden

    (Massachusetts General Hospital, Harvard Medical School
    Harvard University)

Abstract

Stem-cell ageing is thought to contribute to altered tissue maintenance and repair. Older humans experience increased bone marrow failure and poorer haematologic tolerance of cytotoxic injury. Haematopoietic stem cells (HSCs) in older mice have decreased per-cell repopulating activity, self-renewal and homing abilities, myeloid skewing of differentiation, and increased apoptosis with stress. Here we report that the cyclin-dependent kinase inhibitor p16INK4a, the level of which was previously noted to increase in other cell types with age, accumulates and modulates specific age-associated HSC functions. Notably, in the absence of p16INK4a, HSC repopulating defects and apoptosis were mitigated, improving the stress tolerance of cells and the survival of animals in successive transplants, a stem-cell-autonomous tissue regeneration model. Inhibition of p16INK4a may ameliorate the physiological impact of ageing on stem cells and thereby improve injury repair in aged tissue.

Suggested Citation

  • Viktor Janzen & Randolf Forkert & Heather E. Fleming & Yoriko Saito & Michael T. Waring & David M. Dombkowski & Tao Cheng & Ronald A. DePinho & Norman E. Sharpless & David T. Scadden, 2006. "Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a," Nature, Nature, vol. 443(7110), pages 421-426, September.
    • Handle: RePEc:nat:nature:v:443:y:2006:i:7110:d:10.1038_nature05159
    DOI: 10.1038/nature05159
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    Cited by:

    1. Li, Ting & Anderson, James J., 2009. "The vitality model: A way to understand population survival and demographic heterogeneity," Theoretical Population Biology, Elsevier, vol. 76(2), pages 118-131.

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