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Telomere length and replicative aging in human vascular tissues

E Chang1, C B Harley

  • 1Geron Corp., Menlo Park, CA 94025, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 21, 1995
PubMed
Summary

Somatic cell turnover, marked by telomere length, was studied in human vascular tissues. Arterial cells showed faster telomere shortening with age, suggesting replicative senescence contributes to cardiovascular disease.

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Area of Science:

  • Vascular Biology
  • Cellular Aging
  • Atherosclerosis Research

Background:

  • Endothelial injury and cell turnover are implicated in atherosclerosis.
  • Telomere length serves as a marker for somatic cell turnover and replicative history.

Purpose of the Study:

  • To investigate telomere length dynamics in vascular cells.
  • To correlate telomere shortening with cellular aging and hemodynamic stress in different arterial and venous tissues.

Main Methods:

  • Southern analysis of terminal restriction fragments (TRFs) was used to assess telomere length.
  • Telomere lengths were measured in endothelial cells from umbilical veins, iliac arteries, and iliac veins.
  • Telomere shortening rates were analyzed as a function of donor age and tissue type.

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Main Results:

  • Mean telomere length decreased with population doublings in endothelial cell cultures.
  • Iliac artery endothelial cells exhibited a significantly faster rate of telomere shortening with age compared to iliac vein cells.
  • Intimal DNA from iliac arteries showed a greater telomere loss rate than internal thoracic arteries, indicating a non-tissue-specific effect.

Conclusions:

  • Telomere length is a reliable marker for cellular replicative history in vascular tissues.
  • Accelerated telomere shortening in arterial intima suggests a role for focal replicative senescence in cardiovascular disease pathogenesis.
  • Cellular senescence appears more pronounced in the intima than the media under chronic stress.