New targeted approaches for epigenetic age predictions

• Verfasst von: Han, Yang [VerfasserIn]
• Verfasst von: Franzen, Julia [VerfasserIn]
• Verfasst von: Stiehl, Thomas [VerfasserIn]
• Verfasst von: Gobs, Michael [VerfasserIn]
• Verfasst von: Kuo, Chao-Chung [VerfasserIn]
• Verfasst von: Nikolić, Miloš [VerfasserIn]
• Verfasst von: Hapala, Jan [VerfasserIn]
• Verfasst von: Koop, Barbara Elisabeth [VerfasserIn]
• Verfasst von: Strathmann, Klaus [VerfasserIn]
• Verfasst von: Ritz-Timme, Stefanie [VerfasserIn]
• Verfasst von: Wagner, Wolfgang [VerfasserIn]
• Titel: New targeted approaches for epigenetic age predictions
• Verf.angabe: Yang Han, Julia Franzen, Thomas Stiehl, Michael Gobs, Chao-Chung Kuo, Miloš Nikolić, Jan Hapala, Barbara Elisabeth Koop, Klaus Strathmann, Stefanie Ritz-Timme and Wolfgang Wagner
• E-Jahr: 2020
• Jahr: 24 June 2020
• Umfang: 15 S.
• Fussnoten: Gesehen am 13.08.2020
• Titel Quelle: Enthalten in: BMC biology
• Ort Quelle: Berlin : Springer, 2003
• Jahr Quelle: 2020
• Band/Heft Quelle: 18(2020) Artikel-Nummer 71, 15 Seiten
• ISSN Quelle: 1741-7007
• DOI: doi:10.1186/s12915-020-00807-2
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Aging
• Sach-SW: Amplicon sequencing
• Sach-SW: association
• Sach-SW: binding
• Sach-SW: biomarkers
• Sach-SW: Blood
• Sach-SW: blood-cells
• Sach-SW: Buccal swabs
• Sach-SW: combination
• Sach-SW: ctcf
• Sach-SW: DNA methylation
• Sach-SW: dna methylation changes
• Sach-SW: Droplet digital PCR
• Sach-SW: Epigenetic
• Sach-SW: Human
• Sach-SW: methylome
• Sach-SW: pcr
• Sach-SW: signature
• K10plus-PPN: 172701958X

Abstract

Background Age-associated DNA methylation changes provide a promising biomarker for the aging process. While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurements at specific CpGs that better support standardized and cost-effective high-throughput analysis. Results In this study, we utilized 4647 Illumina BeadChip profiles of blood to select CpG sites that facilitate reliable age-predictions based on pyrosequencing. We demonstrate that the precision of DNA methylation measurements can be further increased with droplet digital PCR (ddPCR). In comparison, bisulfite barcoded amplicon sequencing (BBA-seq) gave slightly lower correlation between chronological age and DNA methylation at individual CpGs, while the age-predictions were overall relatively accurate. Furthermore, BBA-seq data revealed that the correlation of methylation levels with age at neighboring CpG sites follows a bell-shaped curve, often associated with a CTCF binding site. We demonstrate that within individual BBA-seq reads the DNA methylation at neighboring CpGs is not coherently modified, but reveals a stochastic pattern. Based on this, we have developed a new approach for epigenetic age predictions based on the binary sequel of methylated and non-methylated sites in individual reads, which reflects heterogeneity in epigenetic aging within a sample. Conclusion Targeted DNA methylation analysis at few age-associated CpGs by pyrosequencing, BBA-seq, and particularly ddPCR enables high precision of epigenetic age-predictions. Furthermore, we demonstrate that the stochastic evolution of age-associated DNA methylation patterns in BBA-seq data enables epigenetic clocks for individual DNA strands.