c-Kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Aging
  • Cell Cycle
  • Cell Lineage
  • Cell Proliferation
  • Mice
  • Mice, Inbred C57BL
  • Myocardium
  • Myocytes, Cardiac
  • Telomere Homeostasis

MeSH Major

  • Aging
  • Cardiomyopathies
  • Hypoxia
  • Myoblasts, Cardiac
  • Proto-Oncogene Proteins c-kit
  • Stem Cell Factor
  • Stem Cell Niche

abstract

  • Hypoxia favors stem cell quiescence, whereas normoxia is required for stem cell activation, but whether cardiac stem cell (CSC) function is regulated by the hypoxic/normoxic state of the cell is currently unknown. A balance between hypoxic and normoxic CSCs may be present in the young heart, although this homeostatic control may be disrupted with aging. Defects in tissue oxygenation occur in the old myocardium, and this phenomenon may expand the pool of hypoxic CSCs, which are no longer involved in myocyte renewal. Here, we show that the senescent heart is characterized by an increased number of quiescent CSCs with intact telomeres that cannot re-enter the cell cycle and form a differentiated progeny. Conversely, myocyte replacement is controlled only by frequently dividing CSCs with shortened telomeres; these CSCs generate a myocyte population that is chronologically young but phenotypically old. Telomere dysfunction dictates their actual age and mechanical behavior. However, the residual subset of quiescent young CSCs can be stimulated in situ by stem cell factor reversing the aging myopathy. Our findings support the notion that strategies targeting CSC activation and growth interfere with the manifestations of myocardial aging in an animal model. Although caution has to be exercised in the translation of animal studies to human beings, our data strongly suggest that a pool of functionally competent CSCs persists in the senescent heart and that this stem cell compartment can promote myocyte regeneration effectively, partly correcting the aging myopathy.

publication date

  • January 3, 2014

has subject area

  • Aging
  • Animals
  • Cardiomyopathies
  • Cell Aging
  • Cell Cycle
  • Cell Lineage
  • Cell Proliferation
  • Hypoxia
  • Mice
  • Mice, Inbred C57BL
  • Myoblasts, Cardiac
  • Myocardium
  • Myocytes, Cardiac
  • Proto-Oncogene Proteins c-kit
  • Stem Cell Factor
  • Stem Cell Niche
  • Telomere Homeostasis

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3959163

Digital Object Identifier (DOI)

  • 10.1161/CIRCRESAHA.114.302500

PubMed ID

  • 24170267

Additional Document Info

start page

  • 41

end page

  • 55

volume

  • 114

number

  • 1