Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevity (2009)

A5 BRÜNING/NIESSENA7 SCHUMACHERB15 HOEIJMAKERSpublications Garinis GA, Uittenboogaard LM, Stachelscheid H, Fousteri M, van Ijcken W, Breit TM, van Steeg H, Mullenders LHF, van der Horst GTJ, Brüning JC, Niessen CM, Hoeijmakers JHJ and Schumacher B, Nature Cell Biol. 2009 May;11(5):604-15.

Abstract:

The accumulation of stochastic DNA damage throughout an organism’s lifespan is thought to contribute to ageing. Conversely, ageing seems to be phenotypically reproducible and regulated through genetic pathways such as the insulin-like growth factor-1 (IGF-1) and growth hormone (GH) receptors, which are central mediators of the somatic growth axis. Here we report that persistent DNA damage in primary cells from mice elicits changes in global gene expression similar to those occurring in various organs of naturally aged animals. We show that, as in ageing animals, the expression of IGF-1 receptor and GH receptor is attenuated, resulting in cellular resistance to IGF-1. This cell-autonomous attenuation is specifically induced by persistent lesions leading to stalling of RNA polymerase II in proliferating, quiescent and terminally differentiated cells; it is exacerbated and prolonged in cells from progeroid mice and confers resistance to oxidative stress. Our findings suggest that the accumulation of DNA damage in transcribed genes in most if not all tissues contributes to the ageing-associated shift from growth to somatic maintenance that triggers stress resistance and is thought to promote longevity.

PubMed

  • Upcoming Events

    1. Women in Science and Society with Sarah Millar

      June 19 @ 1:30 pm - 6:00 pm
    2. 9th PhD student and Postdoc Retreat

      August 22 - August 23
    3. 2nd SFB 829 Connector Meeting

      August 31 @ 3:00 pm - 5:30 pm
    4. International Symposium “Molecular Mechanisms regulating Skin Homeostasis”

      November 12 - November 14
    5. 3rd SFB 829 Connector Meeting

      December 7 @ 3:00 pm - 5:30 pm
  • News

© 2017 SFB 829

Durch die weitere Nutzung der Seite stimmst du der Verwendung von Cookies zu. Weitere Informationen

Die Cookie-Einstellungen auf dieser Website sind auf "Cookies zulassen" eingestellt, um das beste Surferlebnis zu ermöglichen. Wenn du diese Website ohne Änderung der Cookie-Einstellungen verwendest oder auf "Akzeptieren" klickst, erklärst du sich damit einverstanden.

Schließen