The Relationship Between DNA Methylation in Neurotrophic Genes and Age As Evidenced from Three Independent Cohorts: Differences by Delirium Status

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2020 Jul 11

PMID 32650186

Citations 13

Authors

Taku Saito

Patricia R Braun

Sophia Daniel

Sydney S Jellison

Mandy Hellman

Eri Shinozaki

Sangil Lee

Hyunkeun R Cho

Aihide Yoshino

Hiroyuki Toda

Gen Shinozaki

Affiliations

Soon will be listed here.

Abstract

We previously reported the association between DNA methylation (DNAm) of pro-inflammatory cytokine genes and age. In addition, neurotrophic factors are known to be associated with age and neurocognitive disorders. Therefore, we hypothesized that DNAm of neurotrophic genes change with age, especially in delirium patients. DNAm was analyzed using the Illumina HumanMethylation450 or HumanMethylationEPIC BeadChip Kit in 3 independent cohorts: blood from 383 Grady Trauma Project subjects, brain from 21 neurosurgery patients, and blood from 87 inpatients with and without delirium. Both blood and brain samples showed that most of the DNAm of neurotrophic genes were positively correlated with age. Furthermore, DNAm of neurotrophic genes was more positively correlated with age in delirium cases than in non-delirium controls. These findings support our hypothesis that the neurotrophic genes may be epigenetically modulated with age, and this process may be contributing to the pathophysiology of delirium.

Citing Articles

Epigenetic signals associated with delirium replicated across four independent cohorts.

Nishizawa Y, Thompson K, Yamanashi T, Wahba N, Saito T, Marra P Transl Psychiatry. 2024; 14(1):275.

PMID: 38965205 PMC: 11224347. DOI: 10.1038/s41398-024-02986-w.

Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol Withdrawal.

Malewska-Kasprzak M, Skibinska M, Dmitrzak-Weglarz M Brain Sci. 2024; 14(6).

PMID: 38928583 PMC: 11202159. DOI: 10.3390/brainsci14060583.

An Overview of the Epigenetic Modifications in the Brain under Normal and Pathological Conditions.

Lossi L, Castagna C, Merighi A Int J Mol Sci. 2024; 25(7).

PMID: 38612690 PMC: 11011998. DOI: 10.3390/ijms25073881.

NSAIDs use history: impact on the genome-wide DNA methylation profile and possible mechanisms of action.

Marra P, Nishizawa Y, Yamanashi T, Sullivan E, Comp K, Crutchley K Clin Exp Med. 2023; 23(7):3509-3516.

PMID: 37341931 DOI: 10.1007/s10238-023-01119-9.

A Review of Biomarkers in Delirium Superimposed on Dementia (DSD) and Their Clinical Application to Personalized Treatment and Management.

Jahangir S, Allala M, Khan A, Muyolema Arce V, Patel A, Soni K Cureus. 2023; 15(5):e38627.

PMID: 37159618 PMC: 10163832. DOI: 10.7759/cureus.38627.

References

Houseman E, Accomando W, Koestler D, Christensen B, Marsit C, Nelson H . DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics. 2012; 13:86. PMC: 3532182. DOI: 10.1186/1471-2105-13-86. View

Christensen B, Houseman E, Marsit C, Zheng S, Wrensch M, Wiemels J . Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 2009; 5(8):e1000602. PMC: 2718614. DOI: 10.1371/journal.pgen.1000602. View

Mei X, Tong J . The plasma levels of brain-derived neurotrophic factor are positively associated with emergence agitation in the elderly after gastrointestinal surgery. J Anesth. 2016; 30(5):811-6. DOI: 10.1007/s00540-016-2212-3. View

Pal S, Tyler J . Epigenetics and aging. Sci Adv. 2016; 2(7):e1600584. PMC: 4966880. DOI: 10.1126/sciadv.1600584. View

Shinozaki G, Bormann N, Chan A, Zarei K, Sparr N, Klisares M . Identification of Patients With High Mortality Risk and Prediction of Outcomes in Delirium by Bispectral EEG. J Clin Psychiatry. 2019; 80(5). PMC: 7181374. DOI: 10.4088/JCP.19m12749. View

Pidsley R, Zotenko E, Peters T, Lawrence M, Risbridger G, Molloy P . Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol. 2016; 17(1):208. PMC: 5055731. DOI: 10.1186/s13059-016-1066-1. View

Danka Mohammed C, Park J, Nam H, Kim K . MicroRNAs in brain aging. Mech Ageing Dev. 2017; 168:3-9. DOI: 10.1016/j.mad.2017.01.007. View

Tsai P, Spector T, Bell J . Using epigenome-wide association scans of DNA methylation in age-related complex human traits. Epigenomics. 2012; 4(5):511-26. DOI: 10.2217/epi.12.45. View

Ratanatharathorn A, Boks M, Maihofer A, Aiello A, Amstadter A, Ashley-Koch A . Epigenome-wide association of PTSD from heterogeneous cohorts with a common multi-site analysis pipeline. Am J Med Genet B Neuropsychiatr Genet. 2017; 174(6):619-630. PMC: 5592721. DOI: 10.1002/ajmg.b.32568. View

10.

Beveridge N, Santarelli D, Wang X, Tooney P, Webster M, Weickert C . Maturation of the human dorsolateral prefrontal cortex coincides with a dynamic shift in microRNA expression. Schizophr Bull. 2013; 40(2):399-409. PMC: 3932079. DOI: 10.1093/schbul/sbs198. View

11.

Schuurmans M, Shortridge-Baggett L, Duursma S . The Delirium Observation Screening Scale: a screening instrument for delirium. Res Theory Nurs Pract. 2003; 17(1):31-50. DOI: 10.1891/rtnp.17.1.31.53169. View

12.

Horvath S . DNA methylation age of human tissues and cell types. Genome Biol. 2013; 14(10):R115. PMC: 4015143. DOI: 10.1186/gb-2013-14-10-r115. View

13.

Nordlund J, Backlin C, Wahlberg P, Busche S, Berglund E, Eloranta M . Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia. Genome Biol. 2013; 14(9):r105. PMC: 4014804. DOI: 10.1186/gb-2013-14-9-r105. View

14.

Inouye S, van Dyck C, Alessi C, Balkin S, Siegal A, Horwitz R . Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990; 113(12):941-8. DOI: 10.7326/0003-4819-113-12-941. View

15.

Ihara K, Fuchikami M, Hashizume M, Okada S, Kawai H, Obuchi S . The influence of aging on the methylation status of brain-derived neurotrophic factor gene in blood. Int J Geriatr Psychiatry. 2018; 33(10):1312-1318. DOI: 10.1002/gps.4927. View

16.

Gong H, Qian H, Ertl R, Astle C, Wang G, Harrison D . Histone modifications change with age, dietary restriction and rapamycin treatment in mouse brain. Oncotarget. 2015; 6(18):15882-90. PMC: 4599244. DOI: 10.18632/oncotarget.4137. View

17.

Spronk P, Riekerk B, Hofhuis J, Rommes J . Occurrence of delirium is severely underestimated in the ICU during daily care. Intensive Care Med. 2009; 35(7):1276-80. PMC: 2698979. DOI: 10.1007/s00134-009-1466-8. View

18.

Teschendorff A, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D . A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics. 2012; 29(2):189-96. PMC: 3546795. DOI: 10.1093/bioinformatics/bts680. View

19.

Nishimura K, Yokoyama K, Yamauchi N, Koizumi M, Harasawa N, Yasuda T . Sensitivity and specificity of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) for detecting post-cardiac surgery delirium: A single-center study in Japan. Heart Lung. 2015; 45(1):15-20. DOI: 10.1016/j.hrtlng.2015.11.001. View

20.

Aryee M, Jaffe A, Corrada-Bravo H, Ladd-Acosta C, Feinberg A, Hansen K . Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014; 30(10):1363-9. PMC: 4016708. DOI: 10.1093/bioinformatics/btu049. View