Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

Aging

Volumn 8, Issue 7, 2016, Pages 1485-1512

  Horvath, Steve ^a,b   Langfelder, Peter ^a   Kwak, Seung ^c   Aaronson, Jeff ^c   Rosinski, Jim ^c   Vogt, Thomas F ^c   Eszes, Marika ^d   Faull, Richard L M ^d   Curtis, Maurice A ^d   Waldvogel, Henry J ^d   Choi, Oi Wa ^e   Tung, Spencer ^a   Vinters, Harry V ^a   Coppola, Giovanni ^a,e,f   Yang, X William ^a,e,f  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c CHDI MANAGEMENT CHDI FOUNDATION   (United States)

^d UNIVERSITY OF AUCKLAND   (New Zealand)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Biomarker of aging; Brain; DNA methylation; Epigenetic clock; Epigenetics; Huntington's disease

Indexed keywords

ADOLESCENT; ADULT; AGE; AGED; AGING; BRAIN; DNA METHYLATION; FEMALE; GENETICS; HUMAN; HUNTINGTON CHOREA; MALE; METABOLISM; MIDDLE AGED; ONSET AGE; YOUNG ADULT;

ADOLESCENT; ADULT; AGE FACTORS; AGE OF ONSET; AGED; AGING; BRAIN; DNA METHYLATION; FEMALE; HUMANS; HUNTINGTON DISEASE; MALE; MIDDLE AGED; YOUNG ADULT;

EID: 85017019815     PISSN: 19454589     EISSN: None     Source Type: Journal    
DOI: 10.18632/aging.101005     Document Type: Article

References (78)

1. Walker FO. Huntington's disease. Lancet. 2007; 369:218-28.
2. NoAuthorListed A. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. 1993; 72:971-83.
3. Orr HT and Zoghbi HY. Trinucleotide repeat disorders. Annu Rev Neurosci. 2007; 30:575-621.
4. Aylward EH, Harrington DL, Mills JA, Nopoulos PC, Ross CA, Long JD, Liu D, Westervelt HK and Paulsen JS. Regional atrophy associated with cognitive and motor function in prodromal Huntington disease. J Huntingtons Dis. 2013; 2:477-89.
5. Hadzi TC, Hendricks AE, Latourelle JC, Lunetta KL, Cupples LA, Gillis T, Mysore JS, Gusella JF, MacDonald ME, Myers RH and Vonsattel JP. Assessment of cortical and striatal involvement in 523 Huntington disease brains. Neurology. 2012; 79:1708-15.
6. Tabrizi SJ, Scahill RI, Owen G, Durr A, Leavitt BR, Roos RA, Borowsky B, Landwehrmeyer B, Frost C, Johnson H, Craufurd D, Reilmann R, Stout JC, et al. Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data. Lancet Neurol. 2013; 12:637-49.
7. Vonsattel JP and DiFiglia M. Huntington disease. J Neuropathol Exp Neurol. 1998; 57:369-84.
8. Ross CA. Intranuclear neuronal inclusions: a common pathogenic mechanism for glutamine-repeat neurodegenerative diseases? Neuron. 1997; 19:1147-50.
9. Djousse L, Knowlton B, Hayden M, Almqvist EW, Brinkman R, Ross C, Margolis R, Rosenblatt A, Durr A, Dode C, Morrison PJ, Novelletto A, Frontali M, et al. Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease. Am J Med Genet A. 2003; 119A:279-82.
10. Ross CA, Aylward EH, Wild EJ, Langbehn DR, Long JD, Warner JH, Scahill RI, Leavitt BR, Stout JC, Paulsen JS, Reilmann R, Unschuld PG, Wexler A, et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol. 2014; 10:204-16.
11. Gusella JF and Macdonald M. Genetic criteria for Huntington's disease pathogenesis. Brain Res Bull. 2007; 72:78-82.
12. Diguet E, Petit F, Escartin C, Cambon K, Bizat N, Dufour N, Hantraye P, Déglon N and Brouillet E. Normal Aging Modulates the Neurotoxicity of Mutant Huntingtin. PLoS ONE. 2009; 4:e4637.
13. Rakyan VK, Down TA, Maslau S, Andrew T, Yang TP, Beyan H, Whittaker P, McCann OT, Finer S, Valdes AM, Leslie RD, Deloukas P and Spector TD. Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome research. 2010; 20:434-39.
14. Teschendorff AE, Menon U, Gentry-Maharaj A, Ramus SJ, Weisenberger DJ, Shen H, Campan M, Noushmehr H, Bell CG, Maxwell AP, Savage DA, Mueller-Holzner E, Marth C, et al. Agedependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome research. 2010; 20:440-446.
15. Numata S, Ye T, Hyde Thomas M, Guitart-Navarro X, Tao R, Wininger M, Colantuoni C, Weinberger Daniel R, Kleinman Joel E and Lipska Barbara K. DNA Methylation Signatures in Development and Aging of the Human Prefrontal Cortex. Am J Hum Genet. 2012; 90:260-72.
16. Alisch RS, Barwick BG, Chopra P, Myrick LK, Satten GA, Conneely KN and Warren ST. Age-associated DNA methylation in pediatric populations. Genome Res. 2012; 22:623-32.
17. Johansson A, Enroth S and Gyllensten U. Continuous Aging of the Human DNA Methylome Throughout the Human Lifespan. PLoS One. 2013; 8:e67378.
18. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013; 14:115.
19. Horvath S, Erhart W, Brosch M, Ammerpohl O, von Schönfels W, Ahrens M, Heits N, Bell JT, Tsai P-C, Spector TD, Deloukas P, Siebert R, Sipos B, et al. Obesity accelerates epigenetic aging of human liver. Proc Natl Acad Sci U S A 2014; 111:15538-43.
20. Horvath S, Mah V, Lu AT, Woo JS, Choi OW, Jasinska AJ, Riancho JA, Tung S, Coles NS, Braun J, Vinters HV and Coles LS. The cerebellum ages slowly according to the epigenetic clock. Aging (Albany NY). 2015; 7:294-306. doi: 10.18632/aging.100742.
21. Spiers H, Hannon E, Schalkwyk LC, Smith R, Wong CC, O'Donovan MC, Bray NJ and Mill J. Methylomic trajectories across human fetal brain development. Genome research. 2015; 25:338-52.
22. Levine M, Lu A, Bennett D and 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: 10.18632/aging.100864.
23. Guintivano J, Aryee MJ and Kaminsky ZA. A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression. Epigenetics. 2013; 8:290-302.
24. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED and Richardson EP, Jr. Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol. 1985; 44:559-77.
25. Gusella JF and MacDonald ME. Molecular genetics: unmasking polyglutamine triggers in neurodegenerative disease. Nat Rev Neurosci. 2000; 1:109-15.
26. Seong IS, Ivanova E, Lee JM, Choo YS, Fossale E, Anderson M, Gusella JF, Laramie JM, Myers RH, Lesort M and MacDonald ME. HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism. Hum Mol Genet. 2005; 14:2871-80.
27. Biagioli M, Ferrari F, Mendenhall EM, Zhang Y, Erdin S, Vijayvargia R, Vallabh SM, Solomos N, Manavalan P, Ragavendran A, Ozsolak F, Lee JM, Talkowski ME, et al. Htt CAG repeat expansion confers pleiotropic gains of mutant huntingtin function in chromatin regulation. Hum Mol Genet. 2015; 24:2442-57.
28. Lee J, Hwang YJ, Ryu H, Kowall NW and Ryu H. Nucleolar dysfunction in Huntington's disease. Biochim Biophys Acta. 2014; 1842:785-90.
29. Wang F, Fischhaber PL, Guo C and Tang TS. Epigenetic modifications as novel therapeutic targets for Huntington's disease. Epigenomics. 2014; 6:287-97.
30. Valor LM and Guiretti D. What's wrong with epigenetics in Huntington's disease? Neuropharmacology. 2014; 80:103-14.
31. Zhang B and Horvath S. A general framework for weighted gene co-expression network analysis. Statistical Applications in Genetics and Molecular Biology. 2005; 4:17.
32. Langfelder P and Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008; 9:559.
33. Horvath S and Dong J. Geometric Interpretation of Gene Coexpression Network Analysis. PLoS Comput Biol. 2008; 4:1000117.
34. Horvath S. Weighted Network Analysis. Applications in Genomics and Systems Biology: Springer. 2011.
35. Horvath S, Zhang Y, Langfelder P, Kahn R, Boks M, van Eijk K, van den Berg L and Ophoff RA. Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol. 2012; 13:97.
36. Langfelder P and Horvath S. Eigengene networks for studying the relationships between co-expression modules. BMC systems biology. 2007; 1:54.
37. Langfelder P, Mischel PS and Horvath S. When is hub gene selection better than standard meta-analysis? PLoS ONE. 2013; 8:61505.
38. Langfelder P, Cantle J, Chatzopoulou D, Wang N, Gao F, Al-Ramahi I, Lu X, Ramos E, El-Zein K, Zhao Y, Deverasetty S, Tebbe A, Schaab C, et al. Integrated genomics and proteomics to define huntingtin CAG length-dependent molecular networks in HD mouse brains. Nature neuroscience. 2016; 19:623-33.
39. Giles P, Elliston L, Higgs GV, Brooks SP, Dunnett SB and Jones L. Longitudinal analysis of gene expression and behaviour in the HdhQ150 mouse model of Huntington's disease. Brain Res Bull. 2012; 88:199-209.
40. Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, Chevalier B, Johnstone SE, Cole MF, Isono K-i, Koseki H, Fuchikami T, Abe K, et al. Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells. Cell. 2006; 125:301-13.
41. Mielcarek M, Landles C, Weiss A, Bradaia A, Seredenina T, Inuabasi L, Osborne GF, Wadel K, Touller C, Butler R, Robertson J, Franklin SA, Smith DL, et al. HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration. PLoS Biol. 2013; 11:1001717.
42. Vashishtha M, Ng CW, Yildirim F, Gipson TA, Kratter IH, Bodai L, Song W, Lau A, Labadorf A, Vogel-Ciernia A, Troncosco J, Ross CA, Bates GP, et al. Targeting H3K4 trimethylation in Huntington disease. Proc Natl Acad Sci U S A. 2013; 110:3027-36.
43. Seong IS, Woda JM, Song JJ, Lloret A, Abeyrathne PD, Woo CJ, Gregory G, Lee JM, Wheeler VC, Walz T, Kingston RE, Gusella JF, Conlon RA, et al. Huntingtin facilitates polycomb repressive complex 2. Hum Mol Genet. 2010; 19:573-83.
44. Villar-Menendez I, Blanch M, Tyebji S, Pereira-Veiga T, Albasanz JL, Martin M, Ferrer I, Perez-Navarro E and Barrachina M. Increased 5-methylcytosine and decreased 5-hydroxymethylcytosine levels are associated with reduced striatal A2AR levels in Huntington's disease. Neuromolecular Med. 2013; 15:295-309.
45. De Souza RA, Islam SA, McEwen LM, Mathelier A, Hill A, Mah SM, Wasserman WW, Kobor MS and Leavitt BR. DNA Methylation Profiling in Human Huntington's Disease Brain. Hum Mol Genet. 2016. Epub ahead of print.
46. Glajch KE and Sadri-Vakili G. Epigenetic Mechanisms Involved in Huntington's Disease Pathogenesis. J Huntingtons Dis. 2015; 4:1-15.
47. Santos-Rosa H, Schneider R, Bannister AJ, Sherriff J, Bernstein BE, Emre NC, Schreiber SL, Mellor J and Kouzarides T. Active genes are tri-methylated at K4 of histone H3. Nature. 2002; 419:407-11.
48. Ng CW, Yildirim F, Yap YS, Dalin S, Matthews BJ, Velez PJ, Labadorf A, Housman DE and Fraenkel E. Extensive changes in DNA methylation are associated with expression of mutant huntingtin. Proc Natl Acad Sci U S A. 2013; 110:2354-59.
49. Wang F, Yang Y, Lin X, Wang JQ, Wu YS, Xie W, Wang D, Zhu S, Liao YQ, Sun Q, Yang YG, Luo HR, Guo C, et al. Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntington's disease. Hum Mol Genet. 2013; 22:3641-53.
50. Thomas B, Matson S, Chopra V, Sun L, Sharma S, Hersch S, Rosas HD, Scherzer C, Ferrante R and Matson W. A novel method for detecting 7-methyl guanine reveals aberrant methylation levels in Huntington disease. Anal Biochem. 2013; 436:112-20.
51. Horvath S, Garagnani P, Bacalini M, Pirazzini C, Salvioli S, Gentilini D, DiBlasio A, Giuliani C, Tung S, Vinters H and Franceschi C. Accelerated Epigenetic Aging in Down Syndrome. Aging Cell. 2015; 14:491-95.
52. Horvath S and Ritz BR. Increased epigenetic age and granulocyte counts in the blood of Parkinson's disease patients. Aging (Albany NY). 2015; 7:1130-42. doi: 10.18632/aging.100859.
53. Horvath S and Levine AJ. HIV-1 infection accelerates age according to the epigenetic clock. J Infect Dis. 2015; 212:1563-73.
54. Kota LN, Bharath S, Purushottam M, Moily NS, Sivakumar PT, Varghese M, Pal PK and Jain S. Reduced Telomere Length in Neurodegenerative Disorders May Suggest Shared Biology. The Journal of Neuropsychiatry and Clinical Neurosciences. 2014; 27:92-96.
55. Aubert G, Hills M and Lansdorp PM. Telomere Length Measurement-caveats and a critical assessment of the available technologies and tools. Mutation research. 2012; 730:59-67.
56. Xie W, Barr CL, Kim A, Yue F, Lee AY, Eubanks J, Dempster EL and Ren B. Base-resolution analyses of sequence and parent-oforigin dependent DNA methylation in the mouse genome. Cell. 2012; 148:816-31.
57. Li W and Liu M. Distribution of 5-hydroxymethylcytosine in different human tissues. J Nucleic Acids. 2011; 2011:870726.
58. Song CX and He C. The hunt for 5-hydroxymethylcytosine: the sixth base. Epigenomics. 2011; 3:521-23.
59. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M, Tonti-Filippini J, Heyn H, et al. Global epigenomic reconfiguration during mammalian brain development. Science. 2013; 341:1237905.
60. Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE, Pauli-Behn F, Cross MK, Williams BA, Stamatoyannopoulos JA, Crawford GE, Absher DM, Wold BJ and Myers RM. Dynamic DNA methylation across diverse human cell lines and tissues. Genome research. 2013; 23:555-67.
61. Waldvogel HJ, Bullock JY, Synek BJ, Curtis MA, van Roon-Mom WMC and Faull RLM. The collection and processing of human brain tissue for research. Cell and Tissue Banking. 2008; 9:169-79.
62. Waldvogel HJ, Curtis MA, Baer K, Rees MI and Faull RL. Immunohistochemical staining of post-mortem adult human brain sections. Nat Protoc. 2006; 1:2719-32.
63. Dunning M, Barbosa-Morais N, Lynch A, Tavare S and Ritchie M. Statistical issues in the analysis of Illumina data. BMC Bioinformatics. 2008; 9:85.
64. Christensen B, Houseman E, Marsit C, Zheng S, Wrensch M, Wiemels J, Nelson H, Karagas M, Padbury J, Bueno R, Sugarbaker D, Yeh R, Wiencke J, et al. Aging and Environmental Exposures Alter Tissue-Specific DNA Methylation Dependent upon CpG Island Context. PLoS Genet. 2009; 5:1000602.
65. Bollati V, Schwartz J, Wright R, Litonjua A, Tarantini L, Suh H, Sparrow D, Vokonas P and Baccarelli A. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev. 2009; 130:234-39.
66. Vivithanaporn P, Heo G, Gamble J, Krentz H, Hoke A, Gill M and Leistung C. Neurologic disease burden in treated HIV/AIDS predicts survival. Neurology. 2010; 75:1150-58.
67. Day K, Waite L, Thalacker-Mercer A, West A, Bamman M, Brooks J, Myers R and Absher D. Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape. Genome Biol. 2013; 14:102.
68. Bocklandt S, Lin W, Sehl ME, Sanchez FJ, Sinsheimer JS, Horvath S and Vilain E. Epigenetic predictor of age. PLoS ONE. 2011; 6:14821.
69. Garagnani P, Bacalini MG, Pirazzini C, Gori D, Giuliani C, Mari D, Di Blasio AM, Gentilini D, Vitale G, Collino S, Rezzi S, Castellani G, Capri M, et al. Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell. 2012; 11:1132-34.
70. Marioni R, Shah S, McRae A, Chen B, Colicino E, Harris S, Gibson J, Henders A, Redmond P, Cox S, 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.
71. Christiansen L, Lenart A, Tan Q, Vaupel JW, Aviv A, McGue M and Christensen K. DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging Cell. 2016; 15:149-54.
72. 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: 10.18632/aging.100861
73. Marioni RE, Shah S, McRae AF, Ritchie SJ, Muniz-Terrera G, Harris SE, Gibson J, Redmond P, Cox SR and Pattie A. The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. International journal of epidemiology. 2015:77.
74. Aulchenko YS, Ripke S, Isaacs A and van Duijn CM. GenABEL: an R library for genome-wide association analysis. Bioinformatics. 2007; 23:1294-96.
75. Langfelder P and Horvath S. Fast R Functions For Robust Correlations And Hierarchical Clustering. J Stat Software. 2012; 46.
76. Bolstad BM, Irizarry RA, Åstrand M and Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003; 19:185-93.
77. Langfelder P, Zhang B and Horvath S. Defining clusters from a hierarchical cluster tree: the Dynamic Tree Cut library for R. Bioinformatics. 2008; 24:719-20.
78. Miller JA, Cai C, Langfelder P, Geschwind DH, Kurian SM, Salomon DR and Horvath S. Strategies for aggregating gene expression data: The collapseRows R function. BMC Bioinformatics. 2011; 12:322.