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  • Review Article
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The roles of senescence and telomere shortening in cardiovascular disease

Nature Reviews Cardiology volume 10, pages 274–283 (2013)Cite this article

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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.

Key Points

  • Cellular senescence—arrest during the cell cycle (G0)—is involved in the ageing process, and driven by oxidative stress, DNA damage and repair response, inflammation, mitogenic signals, and telomere shortening

  • Cellular senescence parallels the development of atherosclerosis and other pathologies in the vasculature and heart and is, therefore, likely to have a pivotal role in cardiovascular disease

  • Telomere length, usually measured as leucocyte telomere length, is widely considered a marker of biological ageing, is largely inherited, and is modulated by various intrinsic and environmental factors throughout life

  • Endogenous factors causing telomere attrition include ageing, cell division, genetic factors, DNA damage, inflammation, and oxidative stress; telomere attrition can be retarded by genetic factors, telomerase, oestrogen, and antioxidants

  • Environmental factors associated with telomere shortening include poor lifestyle (smoking, excess calories, sedentary lifestyle, alcohol abuse), and severe mental stress, whereas healthy lifestyle is associated with maintenance of long telomeres

  • Telomere length seems to have a key role in cardiovascular disease by driving cells into cell-cycle arrest, senescence, and ultimately apoptosis

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Figure 1: Telomere shortening and cellular senescence.
Figure 2: Human chromosomes and simplified telomere structure.
Figure 3: Telomere attrition, cellular senescence, and cardiovascular disease.

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Authors and Affiliations

  1. Minerva Institute for Medical Research, Biomedicum U2 Helsinki, Helsinki, 00290, Finland

    Frej Fyhrquist & Outi Saijonmaa

  2. Department of Medicine, Geriatric Clinic, University of Helsinki and Helsinki University Central Hospital, PO Box 22, HUS, FIN-00029, Finland

    Timo Strandberg

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  1. Frej Fyhrquist
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  2. Outi Saijonmaa
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  3. Timo Strandberg
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F. Fyhrquist and O. Saijonmaa researched data for the article, and all the authors contributed substantially to discussion of its content. F. Fyhrquist and O. Saijonmaa wrote the article, and all the authors reviewed and edited the manuscript before submission.

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Correspondence to Frej Fyhrquist.

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Fyhrquist, F., Saijonmaa, O. & Strandberg, T. The roles of senescence and telomere shortening in cardiovascular disease. Nat Rev Cardiol 10, 274–283 (2013). https://doi.org/10.1038/nrcardio.2013.30

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