Rejuvenation of aged progenitor cells by exposure to a young systemic environment View Full Text


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Article Info

DATE

2005-02

AUTHORS

Irina M. Conboy, Michael J. Conboy, Amy J. Wagers, Eric R. Girma, Irving L. Weissman, Thomas A. Rando

ABSTRACT

The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem cells. A decline in skeletal muscle stem cell (satellite cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in hepatic progenitor cell proliferation owing to the formation of a complex involving cEBP-alpha and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver. To examine the influence of systemic factors on aged progenitor cells from these tissues, we established parabiotic pairings (that is, a shared circulatory system) between young and old mice (heterochronic parabioses), exposing old mice to factors present in young serum. Notably, heterochronic parabiosis restored the activation of Notch signalling as well as the proliferation and regenerative capacity of aged satellite cells. The exposure of satellite cells from old mice to young serum enhanced the expression of the Notch ligand (Delta), increased Notch activation, and enhanced proliferation in vitro. Furthermore, heterochronic parabiosis increased aged hepatocyte proliferation and restored the cEBP-alpha complex to levels seen in young animals. These results suggest that the age-related decline of progenitor cell activity can be modulated by systemic factors that change with age. More... »

PAGES

760

References to SciGraph publications

  • 1995-11. Culturing satellite cells from living single muscle fiber explants in IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY - ANIMAL
  • 2002-06. Cells that participate in regeneration of skeletal muscle in GENE THERAPY
  • 1996-09. The aging of hematopoietic stem cells in NATURE MEDICINE
  • Journal

    TITLE

    Nature

    ISSUE

    7027

    VOLUME

    433

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature03260

    DOI

    http://dx.doi.org/10.1038/nature03260

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1044062881

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15716955


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