alexa Accelerated ageing: from mechanism to therapy through animal models.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Genetic Syndromes & Gene Therapy

Author(s): Osorio FG, Obaya AJ, LpezOtn C, Freije JM

Abstract Share this page

Abstract Ageing research benefits from the study of accelerated ageing syndromes such as Hutchinson-Gilford progeria syndrome (HGPS), characterized by the early appearance of symptoms normally associated with advanced age. Most HGPS cases are caused by a mutation in the gene LMNA, which leads to the synthesis of a truncated precursor of lamin A known as progerin that lacks the target sequence for the metallopotease FACE-1/ZMPSTE24 and remains constitutively farnesylated. The use of Face-1/Zmpste24-deficient mice allowed us to demonstrate that accumulation of farnesylated prelamin A causes severe abnormalities of the nuclear envelope, hyper-activation of p53 signalling, cellular senescence, stem cell dysfunction and the development of a progeroid phenotype. The reduction of prenylated prelamin A levels in genetically modified mice leads to a complete reversal of the progeroid phenotype, suggesting that inhibition of protein farnesylation could represent a therapeutic option for the treatment of progeria. However, we found that both prelamin A and its truncated form progerin can undergo either farnesylation or geranylgeranylation, revealing the need of targeting both activities for an efficient treatment of HGPS. Using Face-1/Zmpste24-deficient mice as model, we found that a combination of statins and aminobisphosphonates inhibits both types of modifications of prelamin A and progerin, improves the ageing-like symptoms of these mice and extends substantially their longevity, opening a new therapeutic possibility for human progeroid syndromes associated with nuclear-envelope defects. We discuss here the use of this and other animal models to investigate the molecular mechanisms underlying accelerated ageing and to test strategies for its treatment. This article was published in Transgenic Res and referenced in Journal of Genetic Syndromes & Gene Therapy

Relevant Expert PPTs

Relevant Speaker PPTs

  • Uduakobong E Ntuk
    Ethnic variation in the contribution of cardiorespiratory fitness and muscular strength to diabetes: Cross-sectional study of 68,116 UK Biobank participants
    PPT Version | PDF Version
  • Melek Sahin
    Effect of buzzy applıcatıon on paın and ınjectıon satısfactıon ın adult patıents who receıved ıntramuscular ınjectıon
    PPT Version | PDF Version
  • Martha M Sklavos
    Anti-Müllerian hormone deficiency in females with inherited bone marrow failure syndromes
    PDF Version
  • Tao Wu
    The association between TCM syndromes and SCAP polymorphisms insubjects with non-alcoholic fatty liver disease
    PPT Version | PDF Version

Recommended Conferences

  • 3rd World Congress on Human Genetics August 14-15, 2017 Edinburgh, Scotland
    August 14-15, 2017 Edinburgh, Scotland
  • 2nd World Congress on Human Genetics & Genetic Disorders November 02-03, 2017 Toronto, Canada
    November 02-03, 2017 Toronto, Canada

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords