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    DNA Methylation in Aging and Alzheimer's Disease

    • Raymond Cheng
    • Jingmin Shu
    • Hai Chen
    • Ming Li
    • Xiaodong Cheng
    • Li Liu


    Abstract

    DNA methylation undergoes significant changes with age. These alterations play a pivotal role in the development of age-related diseases, including Alzheimer's disease (AD). Recent advancements in DNA methylome profiling have revealed global hypomethylation patterns, particularly within repetitive elements, as well as gene-specific changes that are associated with neurodegeneration. Age-related alterations in DNA methylation have been implicated in the disruption of key cellular processes, such as inflammation and proteostasis, both central to AD pathology. However, several challenges persist in this field. One major issue is the inconsistency of findings across different brain regions and tissue types, which complicates result interpretation. Furthermore, the limited understanding of cell-type specificity raises concerns about the generalizability of findings from bulk tissue analyses. Key questions remain in DNA methylation research related to aging and AD, including elucidating the precise mechanisms driving methylation changes, exploring cell-type specificity, determining the functional consequences of these alterations, and investigating cross-tissue correlations. A deeper understanding of the spatiotemporal dynamics of methylation changes, the underlying mechanisms, and their therapeutic implications is essential to the development of novel prevention and treatment strategies. This review will delve into these findings and challenges, offering insights into future research directions.

    Keywords: DNA Methylation Aging Alzheimer's Disease
    Section

    References

    1. 1. Hara, Y., N. McKeehan, and H.M. Fillit, Translating the biology of aging into novel therapeutics for Alzheimer disease. Neurology, 2019. 92(2): p. 84-93.
    2. 2. Perl, D.P., Neuropathology of Alzheimer's disease. Mt Sinai J Med, 2010. 77(1): p. 32-42.
    3. 3. Dickerson, B.C., et al., The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex, 2009. 19(3): p. 497-510.
    4. 4. DeTure, M.A. and D.W. Dickson, The neuropathological diagnosis of Alzheimer's disease. Mol Neurodegener, 2019. 14(1): p. 32.
    5. 5. Rojo, L.E., et al., Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer's disease. Arch Med Res, 2008. 39(1): p. 1-16.
    6. 6. Weller, R.O., D. Boche, and J.A. Nicoll, Microvasculature changes and cerebral amyloid angiopathy in Alzheimer's disease and their potential impact on therapy. Acta Neuropathol, 2009. 118(1): p. 87-102.
    7. 7. De Plano, L.M., et al., Epigenetic Changes in Alzheimer's Disease: DNA Methylation and Histone Modification. Cells, 2024. 13(8).
    8. 8. Poon, C.H., L.S.R. Tse, and L.W. Lim, DNA methylation in the pathology of Alzheimer's disease: from gene to cognition. Ann N Y Acad Sci, 2020. 1475(1): p. 15-33.
    9. 9. Qazi, T.J., et al., Epigenetics in Alzheimer's Disease: Perspective of DNA Methylation. Mol Neurobiol, 2018. 55(2): p. 1026-1044.
    10. 10. Moore, L.D., T. Le, and G. Fan, DNA methylation and its basic function. Neuropsychopharmacology, 2013. 38(1): p. 23-38.
    11. 11. Field, A.E., et al., DNA Methylation Clocks in Aging: Categories, Causes, and Consequences. Mol Cell, 2018. 71(6): p. 882-895.
    12. 12. Salameh, Y., Y. Bejaoui, and N. El Hajj, DNA Methylation Biomarkers in Aging and Age-Related Diseases. Front Genet, 2020. 11: p. 171.
    13. 13. Reale, A., et al., Counteracting aged DNA methylation states to combat ageing and age-related diseases. Mech Ageing Dev, 2022. 206: p. 111695.
    14. 14. Barrachina, M. and I. Ferrer, DNA methylation of Alzheimer disease and tauopathy-related genes in postmortem brain. J Neuropathol Exp Neurol, 2009. 68(8): p. 880-91.
    15. 15. Bradley-Whitman, M.A. and M.A. Lovell, Epigenetic changes in the progression of Alzheimer's disease. Mech Ageing Dev, 2013. 134(10): p. 486-95.
    16. 16. Kagan, A.B., et al., DNA methyltransferase inhibitor exposure-response: Challenges and opportunities. Clin Transl Sci, 2023. 16(8): p. 1309-1322.
    17. 17. Kaur, G., et al., DNA Methylation: A Promising Approach in Management of Alzheimer's Disease and Other Neurodegenerative Disorders. Biology (Basel), 2022. 11(1).
    18. 18. Gentilini, D., et al., Role of epigenetics in human aging and longevity: genome-wide DNA methylation profile in centenarians and centenarians' offspring. Age (Dordr), 2013. 35(5): p. 1961-73.
    19. 19. Bell, J.T., et al., Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet, 2012. 8(4): p. e1002629.
    20. 20. Bollati, V., et al., Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev, 2009. 130(4): p. 234-9.
    21. 21. Jintaridth, P. and A. Mutirangura, Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences. Physiol Genomics, 2010. 41(2): p. 194-200.
    22. 22. Heyn, H., et al., Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci U S A, 2012. 109(26): p. 10522-7.
    23. 23. Wilson, A.S., B.E. Power, and P.L. Molloy, DNA hypomethylation and human diseases. Biochim Biophys Acta, 2007. 1775(1): p. 138-62.
    24. 24. Bollati, V., et al., Epigenetic effects of shiftwork on blood DNA methylation. Chronobiol Int, 2010. 27(5): p. 1093-104.
    25. 25. Ciccarone, F., et al., DNA methylation dynamics in aging: how far are we from understanding the mechanisms? Mech Ageing Dev, 2018. 174: p. 3-17.
    26. 26. Lu, T., et al., Gene regulation and DNA damage in the ageing human brain. Nature, 2004. 429(6994): p. 883-91.
    27. 27. Iqbal, K., et al., Tau in Alzheimer disease and related tauopathies. Curr Alzheimer Res, 2010. 7(8): p. 656-64.
    28. 28. Mastroeni, D., et al., Epigenetic changes in Alzheimer's disease: decrements in DNA methylation. Neurobiol Aging, 2010. 31(12): p. 2025-37.
    29. 29. Mastroeni, D., et al., Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer's disease. PLoS One, 2009. 4(8): p. e6617.
    30. 30. DeKosky, S.T. and S.W. Scheff, Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol, 1990. 27(5): p. 457-64.
    31. 31. Coppieters, N., et al., Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain. Neurobiol Aging, 2014. 35(6): p. 1334-44.
    32. 32. Rao, J.S., et al., Epigenetic modifications in frontal cortex from Alzheimer's disease and bipolar disorder patients. Transl Psychiatry, 2012. 2(7): p. e132.
    33. 33. Chouliaras, L., et al., Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer's disease patients. Neurobiol Aging, 2013. 34(9): p. 2091-9.
    34. 34. Di Francesco, A., et al., Global changes in DNA methylation in Alzheimer's disease peripheral blood mononuclear cells. Brain Behav Immun, 2015. 45: p. 139-44.
    35. 35. Bjornsson, H.T., et al., Intra-individual change over time in DNA methylation with familial clustering. JAMA, 2008. 299(24): p. 2877-83.
    36. 36. Baylin, S.B. and P.A. Jones, A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer, 2011. 11(10): p. 726-34.
    37. 37. Li, Y. and T.O. Tollefsbol, Age-related epigenetic drift and phenotypic plasticity loss: implications in prevention of age-related human diseases. Epigenomics, 2016. 8(12): p. 1637-1651.
    38. 38. Christensen, B.C., et al., Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet, 2009. 5(8): p. e1000602.
    39. 39. Hannum, G., et al., Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell, 2013. 49(2): p. 359-367.
    40. 40. Issa, J.P., Aging and epigenetic drift: a vicious cycle. J Clin Invest, 2014. 124(1): p. 24-9.
    41. 41. Zampieri, M., et al., Reconfiguration of DNA methylation in aging. Mech Ageing Dev, 2015. 151: p. 60-70.
    42. 42. Thomas, P. and M. Fenech, A review of genome mutation and Alzheimer's disease. Mutagenesis, 2007. 22(1): p. 15-33.
    43. 43. Bagyinszky, E., et al., The genetics of Alzheimer's disease. Clin Interv Aging, 2014. 9: p. 535-51.
    44. 44. Iwata, A., et al., Altered CpG methylation in sporadic Alzheimer's disease is associated with APP and MAPT dysregulation. Hum Mol Genet, 2014. 23(3): p. 648-56.
    45. 45. Fransquet, P.D., et al., DNA methylation analysis of candidate genes associated with dementia in peripheral blood. Epigenomics, 2020. 12(23): p. 2109-2123.
    46. 46. D'Addario, C., et al., Transcriptional and epigenetic phenomena in peripheral blood cells of monozygotic twins discordant for alzheimer's disease, a case report. J Neurol Sci, 2017. 372: p. 211-216.
    47. 47. Tannorella, P., et al., Methylation analysis of multiple genes in blood DNA of Alzheimer's disease and healthy individuals. Neurosci Lett, 2015. 600: p. 143-7.
    48. 48. Tohgi, H., et al., The methylation status of cytosines in a tau gene promoter region alters with age to downregulate transcriptional activity in human cerebral cortex. Neurosci Lett, 1999. 275(2): p. 89-92.
    49. 49. Poirier, J., et al., Apolipoprotein E polymorphism and Alzheimer's disease. Lancet, 1993. 342(8873): p. 697-9.
    50. 50. Wang, S.C., B. Oelze, and A. Schumacher, Age-specific epigenetic drift in late-onset Alzheimer's disease. PLoS One, 2008. 3(7): p. e2698.
    51. 51. Wang, C., et al., Meta-analysis of peripheral blood apolipoprotein E levels in Alzheimer's disease. PLoS One, 2014. 9(2): p. e89041.
    52. 52. Karlsson, I.K., et al., Apolipoprotein E DNA methylation and late-life disease. Int J Epidemiol, 2018. 47(3): p. 899-907.
    53. 53. Nicolia, V., et al., GSK3β 5'-flanking DNA Methylation and Expression in Alzheimer's Disease Patients. Curr Alzheimer Res, 2017. 14(7): p. 753-759.
    54. 54. Akiyama, H., et al., Inflammation and Alzheimer's disease. Neurobiol Aging, 2000. 21(3): p. 383-421.
    55. 55. Fakhoury, M., Microglia and Astrocytes in Alzheimer's Disease: Implications for Therapy. Curr Neuropharmacol, 2018. 16(5): p. 508-518.
    56. 56. Ma, Y., et al., Epigenetic Regulation of Neuroinflammation in Alzheimer's Disease. Cells, 2023. 13(1).
    57. 57. Smith, A.R., et al., Increased DNA methylation near TREM2 is consistently seen in the superior temporal gyrus in Alzheimer's disease brain. Neurobiol Aging, 2016. 47: p. 35-40.
    58. 58. Skaper, S.D., et al., Synaptic Plasticity, Dementia and Alzheimer Disease. CNS Neurol Disord Drug Targets, 2017. 16(3): p. 220-233.
    59. 59. Meftah, S. and J. Gan, Alzheimer's disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression. Front Synaptic Neurosci, 2023. 15: p. 1129036.
    60. 60. Connor, B., et al., Brain-derived neurotrophic factor is reduced in Alzheimer's disease. Brain Res Mol Brain Res, 1997. 49(1-2): p. 71-81.
    61. 61. Nagata, T., et al., Association between DNA Methylation of the BDNF Promoter Region and Clinical Presentation in Alzheimer's Disease. Dement Geriatr Cogn Dis Extra, 2015. 5(1): p. 64-73.
    62. 62. Vasanthakumar, A., et al., Harnessing peripheral DNA methylation differences in the Alzheimer's Disease Neuroimaging Initiative (ADNI) to reveal novel biomarkers of disease. Clin Epigenetics, 2020. 12(1): p. 84.
    63. 63. Miao, Z., Y. Wang, and Z. Sun, The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF. Int J Mol Sci, 2020. 21(4).
    64. 64. Rosa, E. and M. Fahnestock, CREB expression mediates amyloid β-induced basal BDNF downregulation. Neurobiol Aging, 2015. 36(8): p. 2406-13.
    65. 65. Siegmund, K.D., et al., DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS One, 2007. 2(9): p. e895.
    66. 66. Sanchez-Mut, J.V., et al., DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease. Brain, 2013. 136(Pt 10): p. 3018-27.
    67. 67. Anglim, P.P., T.A. Alonzo, and I.A. Laird-Offringa, DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update. Mol Cancer, 2008. 7: p. 81.
    68. 68. Liu, J., et al., Global DNA 5-Hydroxymethylcytosine and 5-Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma. Hepatology, 2019. 69(1): p. 196-208.
    69. 69. Shinagawa, S., et al., DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy in Alzheimer's disease and amnesic mild cognitive impairment patients. Neurosci Lett, 2016. 629: p. 33-37.
    70. 70. Breen, C., et al., Whole genome methylation sequencing in blood identifies extensive differential DNA methylation in late-onset dementia due to Alzheimer's disease. Alzheimers Dement, 2024. 20(2): p. 1050-1062.
    71. 71. Declerck, K. and W. Vanden Berghe, Back to the future: Epigenetic clock plasticity towards healthy aging. Mech Ageing Dev, 2018. 174: p. 18-29.
    72. 72. Bormann, F., et al., Reduced DNA methylation patterning and transcriptional connectivity define human skin aging. Aging Cell, 2016. 15(3): p. 563-71.
    73. 73. Horvath, S., et al., Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol, 2012. 13(10): p. R97.
    74. 74. Horvath, S. and K. Raj, DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet, 2018. 19(6): p. 371-384.
    75. 75. Bell, C.G., et al., DNA methylation aging clocks: challenges and recommendations. Genome Biol, 2019. 20(1): p. 249.
    76. 76. Marioni, R.E., et al., DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol, 2015. 16(1): p. 25.
    77. 77. Gross, A.M., et al., Methylome-wide Analysis of Chronic HIV Infection Reveals Five-Year Increase in Biological Age and Epigenetic Targeting of HLA. Mol Cell, 2016. 62(2): p. 157-168.
    78. 78. Horvath, S. and A.J. Levine, HIV-1 Infection Accelerates Age According to the Epigenetic Clock. J Infect Dis, 2015. 212(10): p. 1563-73.
    79. 79. Marioni, R.E., et al., The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936. Int J Epidemiol, 2015. 44(4): p. 1388-96.
    80. 80. Horvath, S., DNA methylation age of human tissues and cell types. Genome Biol, 2013. 14(10): p. R115.
    81. 81. Zhang, Q., et al., Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing. Genome Med, 2019. 11(1): p. 54.
    82. 82. Yang, Z., et al., Correlation of an epigenetic mitotic clock with cancer risk. Genome Biol, 2016. 17(1): p. 205.
    83. 83. Youn, A. and S. Wang, The MiAge Calculator: a DNA methylation-based mitotic age calculator of human tissue types. Epigenetics, 2018. 13(2): p. 192-206.
    84. 84. Levine, M.E., et al., An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY), 2018. 10(4): p. 573-591.
    85. 85. Lu, A.T., et al., DNA methylation-based estimator of telomere length. Aging (Albany NY), 2019. 11(16): p. 5895-5923.
    86. 86. Lu, A.T., et al., DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY), 2019. 11(2): p. 303-327.
    87. 87. Belsky, D.W., et al., DunedinPACE, a DNA methylation biomarker of the pace of aging. Elife, 2022. 11.
    88. 88. Lin, Q., et al., DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy. Aging (Albany NY), 2016. 8(2): p. 394-401.
    89. 89. Sebastiani, P., et al., Biomarker signatures of aging. Aging Cell, 2017. 16(2): p. 329-338.
    90. 90. Drew, L., Turning back time with epigenetic clocks. Nature, 2022. 601(7893): p. S20-S22.
    91. 91. Vasileva, D., C.M.T. Greenwood, and D. Daley, A Review of the Epigenetic Clock: Emerging Biomarkers for Asthma and Allergic Disease. Genes (Basel), 2023. 14(9).
    92. 92. Milicic, L., et al., Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume. Geroscience, 2022. 44(3): p. 1807-1823.
    93. 93. Levine, M.E., et al., 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(12): p. 1198-211.
    94. 94. Degerman, S., et al., Maintained memory in aging is associated with young epigenetic age. Neurobiol Aging, 2017. 55: p. 167-171.
    95. 95. Vaccarino, V., et al., Epigenetic Age Acceleration and Cognitive Decline: A Twin Study. J Gerontol A Biol Sci Med Sci, 2021. 76(10): p. 1854-1863.
    96. 96. Chouliaras, L., et al., Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study. Epigenomics, 2018. 10(5): p. 585-595.
    97. 97. Starnawska, A., et al., Blood DNA methylation age is not associated with cognitive functioning in middle-aged monozygotic twins. Neurobiol Aging, 2017. 50: p. 60-63.
    98. 98. Beydoun, M.A., et al., Accelerated epigenetic age and cognitive decline among urban-dwelling adults. Neurology, 2020. 94(6): p. e613-e625.
    99. 99. Wu, J.W., et al., Biological age in healthy elderly predicts aging-related diseases including dementia. Sci Rep, 2021. 11(1): p. 15929.
    100. 100. Hillary, R.F., et al., An epigenetic predictor of death captures multi-modal measures of brain health. Mol Psychiatry, 2021. 26(8): p. 3806-3816.
    101. 101. la Torre, A., F. Lo Vecchio, and A. Greco, Epigenetic Mechanisms of Aging and Aging-Associated Diseases. Cells, 2023. 12(8).
    102. 102. Zhu, X., et al., Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention. Signal Transduct Target Ther, 2021. 6(1): p. 245.
    103. 103. Franceschi, C. and J. Campisi, Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci, 2014. 69 Suppl 1: p. S4-9.
    104. 104. Alimohammadi, M., et al., DNA methylation changes and inflammaging in aging-associated diseases. Epigenomics, 2022. 14(16): p. 965-986.
    105. 105. Labbadia, J. and R.I. Morimoto, The biology of proteostasis in aging and disease. Annu Rev Biochem, 2015. 84: p. 435-64.
    106. 106. Hipp, M.S., P. Kasturi, and F.U. Hartl, The proteostasis network and its decline in ageing. Nat Rev Mol Cell Biol, 2019. 20(7): p. 421-435.
    107. 107. Jiang, S. and Y. Guo, Epigenetic Clock: DNA Methylation in Aging. Stem Cells Int, 2020. 2020: p. 1047896.
    108. 108. Davies, M.N., et al., Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biol, 2012. 13(6): p. R43.
    109. 109. Zhang, W., et al., Distinct CSF biomarker-associated DNA methylation in Alzheimer's disease and cognitively normal subjects. Alzheimers Res Ther, 2023. 15(1): p. 78.
    110. 110. Houseman, E.A., et al., DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics, 2012. 13: p. 86.
    111. 111. Guintivano, J., M.J. Aryee, and Z.A. Kaminsky, 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(3): p. 290-302.
    112. 112. Luo, C., et al., Single-cell methylomes identify neuronal subtypes and regulatory elements in mammalian cortex. Science, 2017. 357(6351): p. 600-604.
    113. 113. Liu, H., et al., DNA methylation atlas of the mouse brain at single-cell resolution. Nature, 2021. 598(7879): p. 120-128.
    114. 114. Klein, C., Decoding regulatory elements and brain cell-type shifts offers insights into neuropsychiatric disorders. Sci Adv, 2024. 10(21): p. eadq2375.
    115. 115. Yap, C.X., et al., Brain cell-type shifts in Alzheimer's disease, autism, and schizophrenia interrogated using methylomics and genetics. Sci Adv, 2024. 10(21): p. eadn7655.
    116. 116. Tomita, H., et al., Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain. Biol Psychiatry, 2004. 55(4): p. 346-52.
    117. 117. Sjöholm, L., et al., Evaluation of Post-Mortem Effects on Global Brain DNA Methylation and Hydroxymethylation. Basic Clin Pharmacol Toxicol, 2018. 122(2): p. 208-213.
    118. 118. Jarmasz, J.S., et al., DNA methylation and histone post-translational modification stability in post-mortem brain tissue. Clin Epigenetics, 2019. 11;11(1):5.
    119. 119. Smith, R.G., et al., Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer's disease neuropathology. Alzheimers Dement, 2018. 14(12): p. 1580-1588.

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    “DNA Methylation in Aging and Alzheimer’s Disease”. Human Brain, vol. 3, no. 3, Dec. 2024, https://doi.org/10.37819/hb.3.2027.
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    “DNA Methylation in Aging and Alzheimer’s Disease”. Human Brain, vol. 3, no. 3, Dec. 2024, https://doi.org/10.37819/hb.3.2027.

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    Jingmin Shu
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