title: Prelamin A accumulation and stress conditions induce impaired Oct-1 activity and autophagy in prematurely aged human mesenchymal stem cell.
abstract: Aging, a time-dependent functional decline of biological processes, is the primary risk factor in developing diseases such as cancer, cardiovascular or degenerative diseases. There is a real need to understand the human aging process in order to increase the length of disease-free life, also known as "health span". Accumulation of progerin and prelamin A are the hallmark of a group of premature aging diseases but have also been found during normal cellular aging strongly suggesting similar mechanisms between healthy aging and LMNA-linked progeroid syndromes. How this toxic accumulation contributes to aging (physiological or pathological) remains unclear. Since affected tissues in age-associated disorders and in pathological aging are mainly of mesenchymal origin we propose a model of human aging based on mesenchymal stem cells (hMSCs) which accumulate prelamin A. We demonstrate that prelamin A-accumulating hMSCs have a premature aging phenotype which affects their functional competence in vivo. The combination of prelamin A accumulation and stress conditions enhance the aging phenotype by dysregulating the activity of the octamer binding protein Oct-1This experimental model has been fundamental to identify a new role for Oct-1 in hMSCs aging.
authors.affiliation: Stem Cells and Cell Therapy Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Barakaldo 48903, Spain.
authors.forename: Arantza
authors.initials: A
authors.lastname: Infante
authors.forename: Andrea
authors.initials: A
authors.lastname: Gago
authors.forename: Garbiñe Ruiz
authors.initials: GR
authors.lastname: de Eguino
authors.forename: Teresa
authors.initials: T
authors.lastname: Calvo-Fernández
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gómez-Vallejo
authors.forename: Jordi
authors.initials: J
authors.lastname: Llop
authors.forename: Karin
authors.initials: K
authors.lastname: Schlangen
authors.forename: Ane
authors.initials: A
authors.lastname: Fullaondo
authors.forename: Ana M
authors.initials: AM
authors.lastname: Aransay
authors.forename: Abraham
authors.initials: A
authors.lastname: Martín
authors.forename: Clara I
authors.initials: CI
authors.lastname: Rodríguez
mesh_terms: D000375:Aging / Q000378:metabolism; D019588:Aging, Premature / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D064593:Heterografts; D006801:Humans; D034904:Lamin Type A; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009687:Nuclear Proteins / Q000378:metabolism*; D050811:Octamer Transcription Factor-1 / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011498:Protein Precursors / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016615:Telomere / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
chemical_list: D034904:Lamin Type A; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; D011498:Protein Precursors; D017382:Reactive Oxygen Species; C090764:prelamin A
references.citation: Autophagy. 2005 Oct-Dec;1(3):131-40
references.pmid: 16874025
references.citation: J Biol Chem. 1998 Feb 13;273(7):3963-6
references.pmid: 9461583
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5300-5
references.pmid: 17369361
references.citation: J Gerontol A Biol Sci Med Sci. 2007 Jan;62(1):3-8
references.pmid: 17301031
references.citation: Aging (Albany NY). 2011 Jul;3(7):685-91
references.pmid: 21743107
references.citation: J Cell Sci. 2014 Jan 1;127(Pt 1):147-57
references.pmid: 24155329
references.citation: Mol Biol Cell. 1997 Dec;8(12):2407-19
references.pmid: 9398664
references.citation: Trends Cell Biol. 2011 Oct;21(10):569-76
references.pmid: 21824781
references.citation: Mol Cell Biol. 1986 Oct;6(10):3329-40
references.pmid: 3025588
references.citation: Hum Mol Genet. 2008 Jul 15;17(14):2196-211
references.pmid: 18443001
references.citation: Sci Transl Med. 2012 Jul 25;4(144):144ra103
references.pmid: 22837538
references.citation: J Anat. 2008 Jul;213(1):5-25
references.pmid: 18638067
references.citation: J Cell Biol. 2009 Jan 12;184(1):45-55
references.pmid: 19139261
references.citation: Nat Cell Biol. 2008 Apr;10(4):452-9
references.pmid: 18311132
references.citation: Semin Immunol. 1998 Apr;10(2):155-63
references.pmid: 9618761
references.citation: Cell. 2013 Jun 6;153(6):1194-217
references.pmid: 23746838
references.citation: Stem Cells. 2009 Jun;27(6):1288-97
references.pmid: 19492299
references.citation: Nat Protoc. 2009;4(1):44-57
references.pmid: 19131956
references.citation: Cell. 2008 Jan 11;132(1):27-42
references.pmid: 18191218
references.citation: Nature. 2007 Nov 8;450(7167):165-7
references.pmid: 17994065
references.citation: Am J Med Genet A. 2006 Dec 1;140(23):2603-24
references.pmid: 16838330
references.citation: Cell Death Differ. 2007 Oct;14(10):1759-67
references.pmid: 17612587
references.citation: Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2611-20
references.pmid: 20884875
references.citation: Cell Stem Cell. 2011 Jan 7;8(1):31-45
references.pmid: 21185252
references.citation: Sci Transl Med. 2011 Jun 29;3(89):89ra58
references.pmid: 21715679
references.citation: PLoS One. 2008 May 21;3(5):e2213
references.pmid: 18493317
references.citation: Cancer Res. 2005 Dec 1;65(23):10750-8
references.pmid: 16322220
references.citation: Circulation. 2010 May 25;121(20):2200-10
references.pmid: 20458013
references.citation: Trends Genet. 2008 Dec;24(12):604-12
references.pmid: 18992957
references.citation: Stem Cells. 2007 Mar;25(3):646-54
references.pmid: 17124009
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W133-9
references.pmid: 18487623
references.citation: J Med Genet. 2005 Jun;42(6):e36
references.pmid: 15937076
references.citation: Genes Dev. 1988 Dec;2(12A):1582-99
references.pmid: 2905684
references.citation: Stem Cells Transl Med. 2012 Apr;1(4):309-21
references.pmid: 23197810
references.citation: Genes Dev. 2002 Jun 15;16(12):1472-87
references.pmid: 12080086
references.citation: Aging Cell. 2013 Dec;12(6):955-65
references.pmid: 23795945
references.citation: Aging Cell. 2014 Apr;13(2):292-302
references.pmid: 24305605
references.citation: Mol Aspects Med. 2006 Oct-Dec;27(5-6):403-10
references.pmid: 16973211
references.citation: Science. 2006 May 19;312(5776):1059-63
references.pmid: 16645051
references.citation: Cell Stem Cell. 2013 Dec 5;13(6):691-705
references.pmid: 24315443
references.citation: Autophagy. 2013 Jun 1;9(6):830-49
references.pmid: 23486312
references.citation: Cell. 2001 Oct 5;107(1):67-77
references.pmid: 11595186
references.citation: J Clin Invest. 2006 Mar;116(3):632-4
references.pmid: 16511598
references.citation: Mol Cell Biol. 2004 Feb;24(3):1022-32
references.pmid: 14729950
references.citation: Hum Mol Genet. 2005 Jun 1;14(11):1489-502
references.pmid: 15843404
references.citation: Genes Dev. 1997 May 15;11(10):1207-25
references.pmid: 9171367
references.citation: PLoS Genet. 2012;8(11):e1003048
references.pmid: 23144633
references.citation: Biochem Soc Trans. 2011 Dec;39(6):1775-9
references.pmid: 22103524
references.citation: Genes Dev. 1988 Dec;2(12A):1513-6
references.pmid: 3215510
references.citation: Eur J Histochem. 2011 Oct 19;55(4):e36
references.pmid: 22297442
references.citation: Circulation. 2004 Mar 30;109(12):1543-9
references.pmid: 15023891
references.citation: Cell. 2013 Mar 14;152(6):1365-75
references.pmid: 23498943
references.citation: Nature. 2011 Apr 14;472(7342):221-5
references.pmid: 21346760
references.citation: EMBO J. 2000 Nov 1;19(21):5720-8
references.pmid: 11060023
references.citation: J Clin Invest. 2011 Jul;121(7):2833-44
references.pmid: 21670498
references.citation: Science. 2003 Jun 27;300(5628):2055
references.pmid: 12702809