Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions

  1. Ruben D. Ramirez1,2,
  2. Carmela P. Morales1,2,
  3. Brittney-Shea Herbert1,
  4. Jeffrey M. Rohde1,
  5. Christina Passons1,
  6. Jerry W. Shay1,3, and
  7. Woodring E. Wright1,3
  1. 1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA

Abstract

Telomere shortening is the mechanism underlying replicative aging in fibroblasts. A variety of reports now claim that inactivation of the p16INK4a/pRB pathway is required in addition to telomere maintenance for the immortalization of cells such as skin keratinocytes and breast epithelial cells. We here show that the premature growth arrest of these cell types can be explained by an inadequate culture environment. Providing mesenchymal/epithelial interactions by cultivating the telomerase-expressing cells on feeder layers avoids the growth arrest associated with increased p16INK4a. These results do not support a telomere-independent mechanism of replicative aging.

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Footnotes

  • 2 Present address: Dallas VA, Medical Center, Department of Medicine, Dallas, TX 75216, USA.

  • 3 Corresponding authors.

  • E-MAIL Woodring.Wright{at}utsouthwestern.edu; FAX (214) 648-8694.

  • E-MAIL Jerry.Shay{at}UTSouthwestern.edu; FAX (214) 648-8694.

  • Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.859201.

    • Received October 13, 2000.
    • Accepted December 21, 2000.
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