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Killing the old: cell senescence in atherosclerosis

An Erratum to this article was published on 12 January 2017

This article has been updated

Atherosclerosis is a disease of ageing, and the most common cause of death in the industrialized world. Cell senescence and the therapeutic removal of senescent cells using 'senolytics' are topical areas of science and translational medicine. A new study reports surprising findings on cell senescence and atherosclerosis with important therapeutic implications.

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Figure 1: Effects of cell senescence in atherosclerosis.

Change history

  • 12 January 2017

    In the version of this article initially published online and in print, the red symbol in Figure 1 should be IL-1α, and not IL-1β. The error has been corrected for the HTML and PDF versions of the article.

References

  1. 1

    Childs, B. G. et al. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science 354, 472–477 (2016).

    CAS  Article  Google Scholar 

  2. 2

    Matthews, C. et al. Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ. Res. 99, 156–164 (2006).

    CAS  Article  Google Scholar 

  3. 3

    Gardner, S. E., Humphry, M., Bennett, M. R. & Clarke, M. C. Senescent vascular smooth muscle cells drive inflammation through an interleukin-1α-dependent senescence-associated secretory phenotype. Arterioscler. Thromb. Vasc. Biol. 35, 1963–1974 (2015).

    CAS  Article  Google Scholar 

  4. 4

    Hall, B. M. et al. Aging of mice is associated with p16Ink4a- and β-galactosidase- positive macrophage accumulation that can be induced in young mice by senescent cells. Aging (Albany NY) 8, 1294–1315 (2016).

    CAS  Article  Google Scholar 

  5. 5

    Gil, J. & Withers, D. Ageing: out with the old. Nature 530, 164–165 (2016).

    CAS  Article  Google Scholar 

  6. 6

    Holdt, L. M. et al. Expression of Chr9p21 genes CDKN2B (p15INK4b), CDKN2A (p16INK4a, 14ARF) and MTAP in human atherosclerotic plaque. Atherosclerosis 214, 264–270 (2011).

    CAS  Article  Google Scholar 

  7. 7

    Fuentes, L. et al. Downregulation of the tumour suppressor p16INK4A contributes to the polarisation of human macrophages toward an adipose tissue macrophage (ATM)-like phenotype. Diabetologia 54, 3150–3156 (2011).

    CAS  Article  Google Scholar 

  8. 8

    Cudejko, C. et al. p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages. Blood 118, 2556–2566 (2011).

    CAS  Article  Google Scholar 

  9. 9

    Roos, C. M. et al. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell 15, 973–977 (2016).

    CAS  Article  Google Scholar 

  10. 10

    Stoneman, V. et al. Monocyte/macrophage suppression in CD11b diphtheria toxin receptor transgenic mice differentially affects atherogenesis and established plaques. Circ. Res. 100, 884–893 (2007).

    CAS  Article  Google Scholar 

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Acknowledgements

This work was funded by British Heart Foundation Grants RG/13/14/30314, FS/13/3/30038 and RG/16/8/32388, and the Cambridge NIHR Biomedical Research Centre.

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Correspondence to Martin R. Bennett.

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The authors declare no competing financial interests.

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Bennett, M., Clarke, M. Killing the old: cell senescence in atherosclerosis. Nat Rev Cardiol 14, 8–9 (2017). https://doi.org/10.1038/nrcardio.2016.195

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