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Analysis of expression of growth factor receptors in replicatively and oxidatively senescent human fibroblasts

Jian-Hua Chen1, Susan E Ozanne, C Nicholas Hales

  • 1Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Level 4, Hills Road, Cambridge CB2 2QR, United Kingdom. jhc36@cam.ac.uk

FEBS Letters
|November 3, 2005
PubMed

Insights

Cellular senescence impairs responses to growth factors. Replicative senescence downregulates key growth factor receptors, unlike oxidative senescence, suggesting different underlying mechanisms for reduced mitogen response.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Gerontology

Background:

  • Cellular senescence, a state of irreversible growth arrest, is linked to aging and disease.
  • Senescent cells exhibit altered responses to growth factors (mitogens).
  • The expression of growth factor receptors may be altered during senescence, impacting cellular signaling.

Purpose of the Study:

  • To investigate the expression of major growth factor receptors in human fibroblasts undergoing replicative and oxidative senescence.
  • To determine if downregulation of these receptors contributes to the impaired mitogenic response in different senescence types.

Main Methods:

  • Analysis of mRNA and protein levels of specific growth factor receptors (insulin receptor, PDGF alpha-receptor, PDGF beta-receptor, IGF-1 receptor).
  • Comparison of receptor expression in human fibroblasts exhibiting replicative senescence versus premature oxidative senescence.

Main Results:

  • In replicatively senescent cells, mRNA and protein levels of the insulin receptor and PDGF alpha-receptor were decreased.
  • Protein levels of PDGF beta-receptor and insulin-like growth factor 1 receptor also decreased but remained detectable in replicative senescence.
  • In contrast, major growth factor receptor levels remained unchanged in oxidatively premature senescent cells.

Conclusions:

  • The mechanisms causing diminished responsiveness to mitogens differ between replicative and oxidative senescence.
  • Replicative senescence is associated with a downregulation of specific growth factor receptors.
  • Oxidative senescence may impair mitogen response through pathways independent of major growth factor receptor expression changes.

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