Ischemic stroke patients are biologically older than their chronological age

Aging

Volumn 8, Issue 11, 2016, Pages 2655-2666

  Soriano Tárraga, Carolina ^a   Giralt Steinhauer, Eva ^a   Mola Caminal, Marina ^a   Vivanco Hidalgo, Rosa M ^a   Ois, Angel ^a   Rodríguez Campello, Ana ^a   Cuadrado Godia, Elisa ^a   Sayols Baixeras, Sergi ^b,c   Elosua, Roberto ^b   Roquer, Jaume ^a   Jiménez Conde, Jordi ^a  

^a UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^b INST MUNIC D INVESTIGACIO MEDICA   (Spain)

^c UNIVERSITAT POMPEU FABRA   (Spain)

Author keywords

Aging; Biological age; DNA methylation; Epigenetics; Ischemic stroke

Indexed keywords

ADULT; AGED; AGING; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; CPG ISLAND; DNA METHYLATION; FEMALE; GENETIC EPIGENESIS; GENETICS; HUMAN; MALE; MIDDLE AGED; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; AGING; BRAIN ISCHEMIA; CPG ISLANDS; DNA METHYLATION; EPIGENESIS, GENETIC; FEMALE; HUMANS; MALE; MIDDLE AGED; STROKE;

EID: 85002496971     PISSN: 19454589     EISSN: None     Source Type: Journal    
DOI: 10.18632/aging.101028     Document Type: Article

References (54)

1. Stroke WH. Cerebrovascular accident. World Health Organization. 2014; Available: www.who.int/topics/cerebrovascular_accident/en/.
2. Kissela BM, Khoury JC, Alwell K, Moomaw CJ, Woo D, Adeoye O, Flaherty ML, Khatri P, Ferioli S, De Los Rios La Rosa F, Broderick JP, Kleindorfer DO. Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology. 2012; 79:1781-87. doi.org/10.1212/WNL.0b013e318270401d.
3. Kittner SJ, Singhal AB. Premature atherosclerosis: a major contributor to early-onset ischemic stroke. Neurology. 2013; 80:1272-73. doi.org/10.1212/WNL.0b013e31828ab3a4.
4. Putaala J, Metso AJ, Metso TM, Konkola N, Kraemer Y, Haapaniemi E, Kaste M, Tatlisumak T. Analysis of 1008 consecutive patients aged 15 to 49 with firstever ischemic stroke: the Helsinki young stroke registry. Stroke. 2009; 40:1195-203. doi.org/10.1161/STROKEAHA.108.529883.
5. Nedeltchev K, der Maur TA, Georgiadis D, Arnold M, Caso V, Mattle HP, Schroth G, Remonda L, Sturzenegger M, Fischer U, Baumgartner RW. Ischaemic stroke in young adults: predictors of outcome and recurrence. J Neurol Neurosurg Psychiatry. 2005; 76:191-95. doi.org/10.1136/jnnp.2004.040543.
6. Ferro JM, Massaro AR, Mas J-L. Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol. 2010; 9:1085-96. doi.org/10.1016/S1474-4422(10)70251-9.
7. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010; 28:1057-68. doi.org/10.1038/nbt.1685.
8. Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 2012; 13:97-109. doi:10.1038/nrg3142.
9. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan JB, Gao Y, Deconde R, Chen M, Rajapakse I, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013; 49:359-67. doi.org/10.1016/j.molcel.2012.10.016.
10. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013; 14:R115. doi.org/10.1186/gb-2013-14-10-r115.
11. Marioni RE, Shah S, McRae AF, Chen BH, Colicino E, Harris SE, Gibson J, Henders AK, Redmond P, Cox SR, Pattie A, Corley J, Murphy L, et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 2015; 16:25. doi.org/10.1186/s13059-015-0584-6.
12. Horvath S, Pirazzini C, Bacalini MG, Gentilini D, Di Blasio AM, Delledonne M, Mari D, Arosio B, Monti D, Passarino G, De Rango F, D'Aquila P, Giuliani C, et al. Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. Aging (Albany NY). 2015; 7:1159-70. doi.org/10.18632/aging.100861.
13. Perna L, Zhang Y, Mons U, Holleczek B, Saum K-U, Brenner H. Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. Clin Epigenetics. 2016; 8:64. doi.org/10.1186/s13148-016-0228-z.
14. Christiansen L, Lenart A, Tan Q, Vaupel JW, Aviv A, McGue M, Christensen K. DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell. 2016; 15:149-54. doi.org/10.1111/acel.12421.
15. Oberdoerffer P, Sinclair DA. The role of nuclear architecture in genomic instability and ageing. Nat Rev Mol Cell Biol. 2007; 8:692-702. doi.org/10.1038/nrm2238.
16. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, et al. Distinct DNA methylomes of newborns and centenarians. Proceedings of the National Academy of Sciences of the United States of America. Cancer Epigenetics and Biology Program, Spanish Biomedical Research Centre Network for Epidemiology and Public Health, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, L'Hospitalet, Barcelona, Catalonia 08908, Spain. 2012; 109: 10522-10527. doi:10.1073/pnas.1120658109.
17. Alisch RS, Barwick BG, Chopra P, Myrick LK, Satten GA, Conneely KN, Warren ST. Age-associated DNA methylation in pediatric populations. Genome Res. 2012; 22:623-32. doi.org/10.1101/gr.125187.111.
18. Shah S, McRae AF, Marioni RE, Harris SE, Gibson J, Henders AK, Redmond P, Cox SR, Pattie A, Corley J, Murphy L, Martin NG, Montgomery GW, et al. Genetic and environmental exposures constrain epigenetic drift over the human life course. Genome Res. 2014; 24:1725-33. doi.org/10.1101/gr.176933.114.
19. Bollati V, Schwartz J, Wright R, Litonjua A, Tarantini L, Suh H, Sparrow D, Vokonas P, Baccarelli A. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev. 2009; 130:234-39. doi.org/10.1016/j.mad.2008.12.003.
20. Bell JT, Tsai P-C, Yang T-P, Pidsley R, Nisbet J, Glass D, Mangino M, Zhai G, Zhang F, Valdes A, Shin SY, Dempster EL, Murray RM, et al, and MuTHER Consortium. Epigenome-wide scans identify differentially methylated regions for age and agerelated phenotypes in a healthy ageing population. PLoS Genet. 2012; 8:e1002629. doi.org/10.1371/journal.pgen.1002629.
21. Tsai P-C, Spector TD, Bell JT. Using epigenome-wide association scans of DNA methylation in age-related complex human traits. Epigenomics. 2012; 4:511-26. doi.org/10.2217/epi.12.45.
22. McClay JL, Aberg KA, Clark SL, Nerella S, Kumar G, Xie LY, Hudson AD, Harada A, Hultman CM, Magnusson PK, Sullivan PF, Van Den Oord EJ. A methylome-wide study of aging using massively parallel sequencing of the methyl-CpG-enriched genomic fraction from blood in over 700 subjects. Hum Mol Genet. 2014; 23:1175-85.doi.org/10.1093/hmg/ddt511.
23. Florath I, Butterbach K, Müller H, Bewerunge-Hudler M, Brenner H. Cross-sectional and longitudinal changes in DNA methylation with age: an epigenome-wide analysis revealing over 60 novel age-associated CpG sites. Hum Mol Genet. 2014; 23:1186-201. doi.org/10.1093/hmg/ddt531.
24. Fraga MF, Esteller M. Epigenetics and aging: the targets and the marks. Trends Genet. 2007; 23:413-18. doi.org/10.1016/j.tig.2007.05.008.
25. Blagosklonny MV. Answering the ultimate question "what is the proximal cause of aging?". Aging (Albany NY). 2012; 4:861-77. doi.org/10.18632/aging.100525.
26. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, Diez J, Sanchez-Mut JV, Setien F, Carmona FJ, Puca AA, Sayols S, Pujana MA, et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci USA. 2012; 109:10522-27. doi.org/10.1073/pnas.1120658109.
27. Jones MJ, Goodman SJ, Kobor MS. DNA methylation and healthy human aging. Aging Cell. 2015; 14:924-32. doi.org/10.1111/acel.12349.
28. Boks MP, Derks EM, Weisenberger DJ, Strengman E, Janson E, Sommer IE, Kahn RS, Ophoff RA. The relationship of DNA methylation with age, gender and genotype in twins and healthy controls. PLoS One. 2009; 4:e6767. doi.org/10.1371/journal.pone.0006767.
29. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suñer D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA. 2005; 102:10604-09. doi.org/10.1073/pnas.0500398102.
30. Kaminsky ZA, Tang T, Wang S-C, Ptak C, Oh GH, Wong AH, Feldcamp LA, Virtanen C, Halfvarson J, Tysk C, McRae AF, Visscher PM, Montgomery GW, et al. DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet. 2009; 41:240-45. doi.org/10.1038/ng.286.
31. Teschendorff AE, West J, Beck S. Age-associated epigenetic drift: implications, and a case of epigenetic thrift? Hum Mol Genet. 2013; 22:R7-15. doi.org/10.1093/hmg/ddt375.
32. Singhal AB, Biller J, Elkind MS, Fullerton HJ, Jauch EC, Kittner SJ, Levine DA, Levine SR. Recognition and management of stroke in young adults and adolescents. Neurology. 2013; 81:1089-97. doi.org/10.1212/WNL.0b013e3182a4a451.
33. Smajlovic D. Strokes in young adults: epidemiology and prevention. Vasc Health Risk Manag. 2015; 11:157-64. doi.org/10.2147/VHRM.S53203.
34. Horvath S, Garagnani P, Bacalini MG, Pirazzini C, Salvioli S, Gentilini D, Di Blasio AM, Giuliani C, Tung S, Vinters HV, Franceschi C. Accelerated epigenetic aging in Down syndrome. Aging Cell. 2015; 14:491-95. doi.org/10.1111/acel.12325.
35. Levine ME, Lu AT, Bennett DA, Horvath S. Epigenetic age of the pre-frontal cortex is associated with neuritic plaques, amyloid load, and Alzheimer's disease related cognitive functioning. Aging (Albany NY). 2015; 7:1198-211. doi.org/10.18632/aging.100864.
36. Marioni RE, Shah S, McRae AF, Ritchie SJ, Muniz-Terrera G, Harris SE, Gibson J, Redmond P, Cox SR, Pattie A, Corley J, Taylor A, Murphy L, et al. The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. Int J Epidemiol. 2015; 44:1388-96. doi.org/10.1093/ije/dyu277.
37. Horvath S, Levine AJ. HIV-1 Infection Accelerates Age According to the Epigenetic Clock. J Infect Dis. 2015; 212:1563-73. doi.org/10.1093/infdis/jiv277.
38. Horvath S, Ritz BR. Increased epigenetic age and granulocyte counts in the blood of Parkinson's disease patients. Aging (Albany NY). 2015; 7:1130-42. doi.org/10.18632/aging.100859.
39. Soriano-Tárraga C, Jiménez-Conde J, Giralt-Steinhauer E, Mola M, Ois A, Rodríguez-Campello A, Cuadrado-Godia E, Fernández-Cadenas I, Carrera C, Montaner J, Elosua R, Roquer J, and GeneStroke, and "The Spanish Stroke Genetics Consortium". Global DNA methylation of ischemic stroke subtypes. PLoS One. 2014; 9:e96543. doi.org/10.1371/journal.pone.0096543.
40. Lowe R, Slodkowicz G, Goldman N, Rakyan VK. The human blood DNA methylome displays a highly distinctive profile compared with other somatic tissues. Epigenetics. 2015; 10:274-81. doi.org/10.1080/15592294.2014.1003744.
41. Heyn H, Esteller M. DNA methylation profiling in the clinic: applications and challenges. Nat Rev Genet. 2012; 13:679-92. doi.org/10.1038/nrg3270.
42. Shenker NS, Polidoro S, van Veldhoven K, Sacerdote C, Ricceri F, Birrell MA, Belvisi MG, Brown R, Vineis P, Flanagan JM. Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. Hum Mol Genet. 2013; 22:843-51. doi.org/10.1093/hmg/dds488.
43. Roquer J, Rodríguez-Campello A, Gomis M, Jiménez-Conde J, Cuadrado-Godia E, Vivanco R, Giralt E, Sepúlveda M, Pont-Sunyer C, Cucurella G, Ois A. Acute stroke unit care and early neurological deterioration in ischemic stroke. J Neurol. 2008; 255:1012-17. doi.org/10.1007/s00415-008-0820-z.
44. Soriano-Tárraga C, Jiménez-Conde J, Giralt-Steinhauer E, Mola-Caminal M, Vivanco-Hidalgo RM, Ois A, Rodríguez-Campello A, Cuadrado-Godia E, Sayols-Baixeras S, Elosua R, Roquer J, GENESTROKE Consortium. Epigenome-wide association study identifies TXNIP gene associated with type 2 diabetes mellitus and sustained hyperglycemia. Hum Mol Genet. 2016; 25:609-19. doi.org/10.1093/hmg/ddv493.
45. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993; 24:35-41. doi.org/10.1161/01.STR.24.1.35.
46. Grau M, Subirana I, Elosua R, Solanas P, Ramos R, Masiá R, Cordón F, Sala J, Juvinyà D, Cerezo C, Fitó M, Vila J, Covas MI, Marrugat J. Trends in cardiovascular risk factor prevalence (1995-2000-2005) in northeastern Spain. Eur J Cardiovasc Prev Rehabil. 2007; 14:653-59. doi.org/10.1097/HJR.0b013e3281764429.
47. Pidsley R, Y Wong CC, Volta M, Lunnon K, Mill J, Schalkwyk LC. A data-driven approach to preprocessing Illumina 450K methylation array data. BMC Genomics. 2013; 14:293. doi.org/10.1186/1471-2164-14-293.
48. Touleimat N, Tost J. Complete pipeline for Infinium(®) Human Methylation 450K BeadChip data processing using subset quantile normalization for accurate DNA methylation estimation. Epigenomics. 2012; 4:325-41. doi.org/10.2217/epi.12.21.
49. Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, Irizarry RA. Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014; 30:1363-69. doi.org/10.1093/bioinformatics/btu049.
50. Maksimovic J, Gordon L, Oshlack A. SWAN: subsetquantile within array normalization for illumina infinium HumanMethylation450 BeadChips. Genome Biol. 2012; 13:R44. doi.org/10.1186/gb-2012-13-6-r44.
51. Houseman EA, Accomando WP, Koestler DC, Christensen BC, Marsit CJ, Nelson HH, Wiencke JK, Kelsey KT. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics. 2012; 13:86. doi.org/10.1186/1471-2105-13-86.
52. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2014; Available: http://www.r-project.org.
53. Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012; 28:882-83. doi.org/10.1093/bioinformatics/bts034.
54. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43:e47. doi.org/10.1093/nar/gkv007.