Nonlinear DNA methylation trajectories in aging male mice
Abstract Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow the gap, we investigate the methylation trajectories of male mouse colon at five different time points of aging. Our...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47316-2 |
| _version_ | 1827284204480626688 |
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| author | Maja Olecka Alena van Bömmel Lena Best Madlen Haase Silke Foerste Konstantin Riege Thomas Dost Stefano Flor Otto W. Witte Sören Franzenburg Marco Groth Björn von Eyss Christoph Kaleta Christiane Frahm Steve Hoffmann |
| author_facet | Maja Olecka Alena van Bömmel Lena Best Madlen Haase Silke Foerste Konstantin Riege Thomas Dost Stefano Flor Otto W. Witte Sören Franzenburg Marco Groth Björn von Eyss Christoph Kaleta Christiane Frahm Steve Hoffmann |
| author_sort | Maja Olecka |
| collection | DOAJ |
| description | Abstract Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow the gap, we investigate the methylation trajectories of male mouse colon at five different time points of aging. Our study indicates the existence of sudden hypermethylation events at specific stages of life. Precisely, we identify two epigenomic switches during early-to-midlife (3-9 months) and mid-to-late-life (15-24 months) transitions, separating the rodents’ life into three stages. These nonlinear methylation dynamics predominantly affect genes associated with the nervous system and enrich in bivalently marked chromatin regions. Based on groups of nonlinearly modified loci, we construct a clock-like classifier STageR (STage of aging estimatoR) that accurately predicts murine epigenetic stage. We demonstrate the universality of our clock in an independent mouse cohort and with publicly available datasets. |
| first_indexed | 2024-04-24T09:50:43Z |
| format | Article |
| id | doaj.art-1b1921c741ae4512a8ba29546dcdf82a |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T09:50:43Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-1b1921c741ae4512a8ba29546dcdf82a2024-04-14T11:22:21ZengNature PortfolioNature Communications2041-17232024-04-0115111510.1038/s41467-024-47316-2Nonlinear DNA methylation trajectories in aging male miceMaja Olecka0Alena van Bömmel1Lena Best2Madlen Haase3Silke Foerste4Konstantin Riege5Thomas Dost6Stefano Flor7Otto W. Witte8Sören Franzenburg9Marco Groth10Björn von Eyss11Christoph Kaleta12Christiane Frahm13Steve Hoffmann14Hoffmann Lab, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)Hoffmann Lab, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)Research Group Medical Systems Biology, Institute for Experimental Medicine, University of Kiel and University Medical Center Schleswig-HolsteinDepartment of Neurology, Jena University HospitalHoffmann Lab, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)Hoffmann Lab, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)Research Group Medical Systems Biology, Institute for Experimental Medicine, University of Kiel and University Medical Center Schleswig-HolsteinResearch Group Medical Systems Biology, Institute for Experimental Medicine, University of Kiel and University Medical Center Schleswig-HolsteinDepartment of Neurology, Jena University HospitalInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-HolsteinHoffmann Lab, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)Hoffmann Lab, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)Research Group Medical Systems Biology, Institute for Experimental Medicine, University of Kiel and University Medical Center Schleswig-HolsteinDepartment of Neurology, Jena University HospitalHoffmann Lab, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)Abstract Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow the gap, we investigate the methylation trajectories of male mouse colon at five different time points of aging. Our study indicates the existence of sudden hypermethylation events at specific stages of life. Precisely, we identify two epigenomic switches during early-to-midlife (3-9 months) and mid-to-late-life (15-24 months) transitions, separating the rodents’ life into three stages. These nonlinear methylation dynamics predominantly affect genes associated with the nervous system and enrich in bivalently marked chromatin regions. Based on groups of nonlinearly modified loci, we construct a clock-like classifier STageR (STage of aging estimatoR) that accurately predicts murine epigenetic stage. We demonstrate the universality of our clock in an independent mouse cohort and with publicly available datasets.https://doi.org/10.1038/s41467-024-47316-2 |
| spellingShingle | Maja Olecka Alena van Bömmel Lena Best Madlen Haase Silke Foerste Konstantin Riege Thomas Dost Stefano Flor Otto W. Witte Sören Franzenburg Marco Groth Björn von Eyss Christoph Kaleta Christiane Frahm Steve Hoffmann Nonlinear DNA methylation trajectories in aging male mice Nature Communications |
| title | Nonlinear DNA methylation trajectories in aging male mice |
| title_full | Nonlinear DNA methylation trajectories in aging male mice |
| title_fullStr | Nonlinear DNA methylation trajectories in aging male mice |
| title_full_unstemmed | Nonlinear DNA methylation trajectories in aging male mice |
| title_short | Nonlinear DNA methylation trajectories in aging male mice |
| title_sort | nonlinear dna methylation trajectories in aging male mice |
| url | https://doi.org/10.1038/s41467-024-47316-2 |
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