The roles of senescence and telomere shortening in cardiovascular disease

Nat Rev Cardiol. 2013 May;10(5):274-83. doi: 10.1038/nrcardio.2013.30. Epub 2013 Mar 12.

Abstract

Cellular senescence, defined as arrest during the cell cycle (G₀), is involved in the complex process of the biological ageing of tissues, organs, and organisms. Senescence is driven by many factors including oxidative stress, the DNA damage and repair response, inflammation, mitogenic signals, and telomere shortening. Telomeres are shortened by each cell division until a critical length is reached and dysfunction ensues. DNA-repair pathways are then recruited and cells enter senescence, losing their capacity to proliferate. In addition to cell division, factors causing telomere shortening include DNA damage, inflammation, and oxidative stress. Both cardiovascular risk factors and common cardiovascular diseases, such as atherosclerosis, heart failure, and hypertension, are associated with short leucocyte telomeres, but causality remains undetermined. Telomere length does not satisfy strict criteria for being a biomarker of ageing, but adds predictive power to that of chronological age, and can be considered a marker of cardiovascular ageing. The 'senescence-associated secretory phenotype' of senescent cells exerts a wide range of autocrine and paracrine activities aimed at tissue repair, but which also fuel degenerative and proliferative alterations that contribute to cardiovascular disease. In this Review, the relationship between telomere shortening, senescence, and cardiovascular disease is discussed.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / therapy
  • Cellular Senescence*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Phenotype
  • Telomere / metabolism
  • Telomere / pathology*
  • Telomere Shortening*