Characterising developmental dynamics of adult epigenetic clock sitesResearch in context
Summary: Background: DNA methylation (DNAm), an epigenetic mechanism that regulates gene activity in response to genetic and environmental influences, changes as we age. DNAm at specific sites on the genome can be used to calculate ‘epigenetic clocks’, which are powerful biomarkers of age, as well...
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Elsevier
2024-11-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396424004614 |
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| author | Rosa H. Mulder Alexander Neumann Janine F. Felix Matthew Suderman Charlotte A.M. Cecil |
| author_facet | Rosa H. Mulder Alexander Neumann Janine F. Felix Matthew Suderman Charlotte A.M. Cecil |
| author_sort | Rosa H. Mulder |
| collection | DOAJ |
| description | Summary: Background: DNA methylation (DNAm), an epigenetic mechanism that regulates gene activity in response to genetic and environmental influences, changes as we age. DNAm at specific sites on the genome can be used to calculate ‘epigenetic clocks’, which are powerful biomarkers of age, as well as of ageing. However, little is known about how these clock sites ‘behave’ during development and what factors influence their variability in early life. This knowledge could be used to optimise healthy ageing well before the onset of age-related conditions. Methods: We leveraged results from two longitudinal population-based cohorts (N = 5019 samples from 2348 individuals) to characterise trajectories of adult clock sites from birth to early adulthood. To explore what factors may drive early individual differences at these clock sites, we also tested for enrichment of genetic factors and prenatal exposures based on existing epigenome-wide association meta-analyses. Findings: We find that clock sites (i) diverge widely in their developmental trajectories, often showing non-linear change over time; (ii) are substantially more likely than non-clock sites to vary between individuals already from birth, differences that are predictive of DNAm variation at later ages; and (iii) show enrichment for genetic influences and prenatal environmental exposures, including prenatal smoking, diet and maternal physical health conditions. Interpretation: These results suggests that age(ing)-related epigenetic processes might originate—and differ between individuals—already very early in development. Understanding what drives these differences may in future help us to devise better strategies to promote healthy ageing. Funding: This research was conducted while C.A.M.C. was a Hevolution/AFAR New Investigator Awardee in Aging Biology and Geroscience Research. Full personal funding details, as well as cohort funding details, can be found in the Acknowledgements. |
| format | Article |
| id | doaj-art-6a8cef2665c44917870adb77c890e6b7 |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-6a8cef2665c44917870adb77c890e6b72024-11-14T04:32:30ZengElsevierEBioMedicine2352-39642024-11-01109105425Characterising developmental dynamics of adult epigenetic clock sitesResearch in contextRosa H. Mulder0Alexander Neumann1Janine F. Felix2Matthew Suderman3Charlotte A.M. Cecil4Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Corresponding author. Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, PO Box 2060, 3000 CB, Rotterdam, The Netherlands.Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the NetherlandsThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the NetherlandsMRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UKDepartment of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the NetherlandsSummary: Background: DNA methylation (DNAm), an epigenetic mechanism that regulates gene activity in response to genetic and environmental influences, changes as we age. DNAm at specific sites on the genome can be used to calculate ‘epigenetic clocks’, which are powerful biomarkers of age, as well as of ageing. However, little is known about how these clock sites ‘behave’ during development and what factors influence their variability in early life. This knowledge could be used to optimise healthy ageing well before the onset of age-related conditions. Methods: We leveraged results from two longitudinal population-based cohorts (N = 5019 samples from 2348 individuals) to characterise trajectories of adult clock sites from birth to early adulthood. To explore what factors may drive early individual differences at these clock sites, we also tested for enrichment of genetic factors and prenatal exposures based on existing epigenome-wide association meta-analyses. Findings: We find that clock sites (i) diverge widely in their developmental trajectories, often showing non-linear change over time; (ii) are substantially more likely than non-clock sites to vary between individuals already from birth, differences that are predictive of DNAm variation at later ages; and (iii) show enrichment for genetic influences and prenatal environmental exposures, including prenatal smoking, diet and maternal physical health conditions. Interpretation: These results suggests that age(ing)-related epigenetic processes might originate—and differ between individuals—already very early in development. Understanding what drives these differences may in future help us to devise better strategies to promote healthy ageing. Funding: This research was conducted while C.A.M.C. was a Hevolution/AFAR New Investigator Awardee in Aging Biology and Geroscience Research. Full personal funding details, as well as cohort funding details, can be found in the Acknowledgements.http://www.sciencedirect.com/science/article/pii/S2352396424004614Epigenetic clocksDNA methylationDevelopmentEarly originsThe generation R studyALSPAC |
| spellingShingle | Rosa H. Mulder Alexander Neumann Janine F. Felix Matthew Suderman Charlotte A.M. Cecil Characterising developmental dynamics of adult epigenetic clock sitesResearch in context EBioMedicine Epigenetic clocks DNA methylation Development Early origins The generation R study ALSPAC |
| title | Characterising developmental dynamics of adult epigenetic clock sitesResearch in context |
| title_full | Characterising developmental dynamics of adult epigenetic clock sitesResearch in context |
| title_fullStr | Characterising developmental dynamics of adult epigenetic clock sitesResearch in context |
| title_full_unstemmed | Characterising developmental dynamics of adult epigenetic clock sitesResearch in context |
| title_short | Characterising developmental dynamics of adult epigenetic clock sitesResearch in context |
| title_sort | characterising developmental dynamics of adult epigenetic clock sitesresearch in context |
| topic | Epigenetic clocks DNA methylation Development Early origins The generation R study ALSPAC |
| url | http://www.sciencedirect.com/science/article/pii/S2352396424004614 |
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