Hutchinson–Gilford progeria syndrome as a model fo

Authors: Jonathan A Brassard Natalie Fekete Alain Garnier Corinne A Hoesli

Publish Date: 2015/09/02

Volume: 17, Issue: 1, Pages: 129-145

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Abstract

HutchinsonGilford progeria syndrome HGPS is a premature aging disorder caused by a de novo genetic mutation that leads to the accumulation of a splicing isoform of lamin A termed progerin Progerin expression alters the organization of the nuclear lamina and chromatin The life expectancy of HGPS patients is severely reduced due to critical cardiovascular defects Progerin also accumulates in an agedependent manner in the vascular cells of adults that do not carry genetic mutations associated with HGPS The molecular mechanisms that lead to vascular dysfunction in HGPS may therefore also play a role in vascular aging The vascular phenotypic and molecular changes observed in HGPS are strikingly similar to those seen with age including increased senescence altered mechanotransduction and stem cell exhaustion This article discusses the similarities and differences between agedependent and HGPSrelated vascular aging to highlight the relevance of HGPS as a model for vascular aging Induced pluripotent stem cells derived from HGPS patients are suggested as an attractive model to study vascular aging in order to develop novel approaches to treat cardiovascular diseaseWe thank Dr Gerardo Ferbeyre Université de Montréal for reviewing this manuscript and for his insightful comments and discussion We also thank Professor Gaétan Laroche Université Laval and Centre de recherche du CHU de Québec and William L Stanford Ottawa Hospital Research Institute and University of Ottawa for useful discussions We thank the Canadian Stem Cell Network JB AG and CH Pfizer Ltd and Pfizer Canada Inc See the Potential postdoctoral fellowship awarded to CH the Canadian Institutes of Health Research MOP142285 SaintGobain Ceramics Plastics Inc the ThéCell Network and the Centre québécois sur les matériaux fonctionnels CQMF strategic cluster of the Fonds de recherche du Québec—Nature et technologies for their financial support

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