Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Cell Biol. 2008 Apr;10(4):452-9. doi: 10.1038/ncb1708. Epub 2008 Mar 2.

Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing.

Author information

  • 1National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. scaffidp@mail.nih.gov

Abstract

The premature-ageing disease Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A. Progerin is also expressed sporadically in wild-type cells and has been linked to physiological ageing. Cells from HGPS patients exhibit extensive nuclear defects, including abnormal chromatin structure and increased DNA damage. At the organismal level, HGPS affects several tissues, particularly those of mesenchymal origin. How the cellular defects of HGPS cells lead to the organismal defects has been unclear. Here, we provide evidence that progerin interferes with the function of human mesenchymal stem cells (hMSCs). We find that expression of progerin activates major downstream effectors of the Notch signalling pathway. Induction of progerin in hMSCs changes their molecular identity and differentiation potential. Our results support a model in which accelerated ageing in HGPS patients, and possibly also physiological ageing, is the result of adult stem cell dysfunction and progressive deterioration of tissue functions.

PMID:
18311132
[PubMed - indexed for MEDLINE]
PMCID:
PMC2396576
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk