Specific premature epigenetic aging of cartilage in osteoarthritis.
Osteoarthritis (OA) is a disease affecting multiple tissues of the joints in the elderly, but most notably articular cartilage. Premature biological aging has been described in this tissue and in blood cells, suggesting a systemic component of premature aging in the pathogenesis of OA. Here, we have explored epigenetic aging in OA at the local (cartilage and bone) and systemic (blood) levels. Two DNA methylation age-measures (DmAM) were used: the multi-tissue age estimator for cartilage and bone; and a blood-specific biomarker for blood. Differences in DmAM between OA patients and controls showed an accelerated aging of 3.7 years in articular cartilage (95% CI = 1.1 to 6.3,P= 0.008) of OA patients. By contrast, no difference in epigenetic aging was observed in bone (0.04 years; 95% CI = -1.8 to 1.9,P= 0.3) and in blood (-0.6 years; 95% CI = -1.5 to 0.3,P= 0.2) between OA patients and controls. Therefore, premature epigenetic aging according to DNA methylation changes was specific of OA cartilage, adding further evidence and insight on premature aging of cartilage as a component of OA pathogenesis that reflects damage and vulnerability.
Laboratorio Investigacion 10 and Rheumatology Unit, Instituto Investigacion Sanitaria, Hospital Clinico Universitario de Santiago, Travesia Choupana, sn. 15706- Santiago de Compostela, Spain.
Laura
L
Vidal-Bralo
Laboratorio Investigacion 10 and Rheumatology Unit, Instituto Investigacion Sanitaria, Hospital Clinico Universitario de Santiago, Travesia Choupana, sn. 15706- Santiago de Compostela, Spain.
Yolanda
Y
Lopez-Golan
Laboratorio Investigacion 10 and Rheumatology Unit, Instituto Investigacion Sanitaria, Hospital Clinico Universitario de Santiago, Travesia Choupana, sn. 15706- Santiago de Compostela, Spain.
Antonio
A
Mera-Varela
Grupo de Reumatología, Instituto de Investigación Biomédica de A Coruña. Complexo Hospitalario Universitario de A Coruña, Universidade da Coruña. As Xubias, sn. 15006- A Coruña, Spain.
Ignacio
I
Rego-Perez
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Steve
S
Horvath
Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, A1B- St. John's, NL, Canada.
Yuhua
Y
Zhang
Department of Internal Medicine, Hospital U. M. Valdecilla-IDIVAL, University of Cantabria, Cardenal Herrera Oria, 39011, Santander, Spain.
Álvaro
Á
Del Real
Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, A1B- St. John's, NL, Canada.
Guangju
G
Zhai
Grupo de Reumatología, Instituto de Investigación Biomédica de A Coruña. Complexo Hospitalario Universitario de A Coruña, Universidade da Coruña. As Xubias, sn. 15006- A Coruña, Spain.
Francisco J
FJ
Blanco
Department of Internal Medicine, Hospital U. M. Valdecilla-IDIVAL, University of Cantabria, Cardenal Herrera Oria, 39011, Santander, Spain.
Jose A
JA
Riancho
Laboratorio Investigacion 10 and Rheumatology Unit, Instituto Investigacion Sanitaria, Hospital Clinico Universitario de Santiago, Travesia Choupana, sn. 15706- Santiago de Compostela, Spain.
Juan J
JJ
Gomez-Reino
Laboratorio Investigacion 10 and Rheumatology Unit, Instituto Investigacion Sanitaria, Hospital Clinico Universitario de Santiago, Travesia Choupana, sn. 15706- Santiago de Compostela, Spain.
Antonio
A
Gonzalez
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019588:Aging, Premature; D002356:Cartilage / Q000473:pathology*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology*
DNA methylation; biological age; epigenetics; osteoarthritis; telomere length shortening
PLoS One. 2011;6(6):e14821
21731603
Aging Cell. 2015 Jun;14(3):491-5
25678027
RMD Open. 2015 Jun 02;1(1):e000077
26535137
Int J Epidemiol. 2015 Aug;44(4):1388-96
25617346
BMC Musculoskelet Disord. 2015 Nov 17;16:359
26578262
Genome Biol. 2015 Dec 17;16:266
26673150
Genome Biol. 2014 Apr 01;15(4):r54
24690455
Arthritis Rheum. 2008 Sep 15;59(9):1207-13
18759314
Mutat Res. 2010 Jan 5;683(1-2):68-73
19879280
Arthritis Res Ther. 2012 Jan 18;14(1):R12
22257826
Genome Biol. 2013;14(10):R115
24138928
Front Genet. 2016 Jul 14;7:126
27471517
Clin Epigenetics. 2016 Jun 03;8:64
27274774
Arthritis Rheum. 2012 Jun;64(6):1697-707
22392533
Arthritis Rheum. 2013 Jan;65(1):197-205
23124911
Ann Rheum Dis. 2016 Oct;75(10):1749-56
26543059
Hum Mol Genet. 2014 Mar 1;23(5):1186-201
24163245
Mol Pain. 2012 Feb 12;8:12
22325162
Cell. 2013 Jun 6;153(6):1194-217
23746838
Arthritis Rheumatol. 2015 Jul;67(7):1798-805
25778744
Hum Mol Genet. 2013 Oct 15;22(R1):R7-R15
23918660
Ann Rheum Dis. 2015 Jan;74(1):74-81
24047870
Arthritis Care Res (Hoboken). 2013 Dec;65(12):1951-8
23925995
Mech Ageing Dev. 2013 Sep;134(9):367-72
23872258
Aging Cell. 2016 Feb;15(1):149-54
26594032
Aging Cell. 2002 Oct;1(1):57-65
12882354
Aging Cell. 2015 Aug;14(4):644-58
25754370
BMJ. 2011 Mar 08;342:d1165
21385807
Genome Biol. 2015 Jan 30;16:25
25633388
Aging (Albany NY). 2015 Dec;7(12 ):1159-70
26678252
Sci Rep. 2015 May 18;5:10145
25984812
Clin Epigenetics. 2016 Feb 26;8:21
26925173
BMC Musculoskelet Disord. 2015 Oct 09;16:287
26453558
Aging (Albany NY). 2016 Aug;8(8):1703-17
27490266
Mol Cell. 2013 Jan 24;49(2):359-67
23177740
Bone. 2012 Aug;51(2):241-8
22487298
Curr Opin Rheumatol. 2011 Sep;23(5):492-6
21709557
Ann Rheum Dis. 2014 Apr;73(4):668-77
23505229
Aging (Albany NY). 2015 May;7(5):294-306
26000617
Nucleic Acids Res. 2005 Jun 15;33(10):e95
15958788
Front Genet. 2016 Feb 12;7:13
26904101
Ann Rheum Dis. 2006 Nov;65(11):1444-8
17038452
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15538-43
25313081
Behav Res Methods. 2007 May;39(2):175-91
17695343
Genome Biol. 2014 Feb 03;15(2):R24
24490752
Sci Rep. 2015 Dec 07;5:17602
26639398
Arthritis Res Ther. 2006;8(3):R55
16542493
Aging (Albany NY). 2010 Dec;2(12):990-8
21098883
Arthritis Rheum. 1990 Nov;33(11):1601-10
2242058