Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2019 Mar 1;38(5):e101571.
doi: 10.15252/embj.2019101571. Epub 2019 Feb 15.

Length doesn't matter-telomere damage triggers cellular senescence in the ageing heart

Thomas Brand  1
Affiliations
Comment

Length doesn't matter-telomere damage triggers cellular senescence in the ageing heart

Thomas Brand. EMBO J. .

Abstract

Telomere shortening induces cellular senescence in proliferative cells. Yet, it is presently unclear how it is triggered in post‐mitotic cells such as cardiac myocytes. A new study by Anderson et al (2019) reports that during ageing of the heart, cellular senescence develops independently of telomere length, but is evoked by DNA damage, which preferentially accumulates at the telomere. Removal of senescent cells using senolytic drugs ameliorated cardiac hypertrophy and fibrosis and may inform novel approaches to improve the conditions for the ageing heart.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Cellular senescence in cardiac myocytes is trigged by persistent DNA damage at telomeres
In the ageing heart, decreased expression of mitochondrial electron transport proteins leads to increased production of reactive oxygen species (ROS) and is causing persistent DNA damage at the telomere. A DNA damage response (DDR) is triggered, leading to increased expression of senescence genes and a senescence‐associated secretory phenotype (SASP). These changes are responsible for the development of cardiac senescence. Senolytic drugs are able to improve the conditions for the ageing heart. However, also lifestyle changes impacting on mitochondrial function and ROS production may have an effect.
See this image and copyright information in PMC

Comment on

  • Length-independent telomere damage drives post-mitotic cardiomyocyte senescence.
    Anderson R, Lagnado A, Maggiorani D, Walaszczyk A, Dookun E, Chapman J, Birch J, Salmonowicz H, Ogrodnik M, Jurk D, Proctor C, Correia-Melo C, Victorelli S, Fielder E, Berlinguer-Palmini R, Owens A, Greaves LC, Kolsky KL, Parini A, Douin-Echinard V, LeBrasseur NK, Arthur HM, Tual-Chalot S, Schafer MJ, Roos CM, Miller JD, Robertson N, Mann J, Adams PD, Tchkonia T, Kirkland JL, Mialet-Perez J, Richardson GD, Passos JF. Anderson R, et al. EMBO J. 2019 Mar 1;38(5):e100492. doi: 10.15252/embj.2018100492. Epub 2019 Feb 8. EMBO J. 2019. PMID: 30737259 Free PMC article.

References

    1. Anderson R, Lagnado A, Maggiorani D, Walaszczyk A, Dookun E, Chapman J, Birch J, Salmonowicz H, Ogrodnik M, Jurk D, Proctor C, Correia‐Melo C, Victorelli S, Fielder E, Berlinguer‐Palmini R, Owens A, Greaves L, Kolsky KL, Parini A, Douin‐Echinard V et al (2019) Length‐independent telomere damage drives post‐mitotic cardiomyocyte senescence. EMBO J 38: e100492 - PMC - PubMed
    1. Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A, Khazaie K, Miller JD, van Deursen JM (2016) Naturally occurring p16 (Ink4a)‐positive cells shorten healthy lifespan. Nature 530: 184–189 - PMC - PubMed
    1. Bergmann O, Zdunek S, Felker A, Salehpour M, Alkass K, Bernard S, Sjostrom SL, Szewczykowska M, Jackowska T, Dos Remedios C, Malm T, Andrä M, Jashari R, Nyengaard JR, Possnert G, Jovinge S, Druid H, Frisén J (2015) Dynamics of cell generation and turnover in the human heart. Cell 161: 1566–1575 - PubMed
    1. Coppé JP, Desprez PY, Krtolica A, Campisi J (2010) The senescence‐associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 5: 99–118 - PMC - PubMed
    1. Correia‐Melo C, Marques FD, Anderson R, Hewitt G, Hewitt R, Cole J, Carroll BM, Miwa S, Birch J, Merz A, Rushton MD, Charles M, Jurk D, Tait SW, Czapiewski R, Greaves L, Nelson G, Bohlooly‐Y M, Rodriguez‐Cuenca S, Vidal‐Puig A et al (2016) Mitochondria are required for pro‐ageing features of the senescent phenotype. EMBO J 35: 724–742 - PMC - PubMed