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Synchrony and asynchrony between an epigenetic clock and developmental timing [EPIC array]

ABSTRACT: Genome wide DNA methylation profiling of human fetal retina samples. The Illumina Infinium DNA methylation Beadchip was used to obtain DNA methylation profiles in human fetal retina samples that were cultured in different ways. To better undrestand the relationship between developmental stage and epigenetic age (measured by the Horvath clock based on 353 CpGs as detailed in pubmed identifier: 24138928), we analyzed the highly regular sequence of developmental stage in the human neural retina. Findings: epigenetic age of fetal retina is highly correlated with chronological age. We find that epigenetic aging progresses normally in vitro. The correlation is retained in stem cell derived organoids but is accelerated in individuals with Down syndrome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE124568 | GEO | 2020/03/12

REPOSITORIES: GEO

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Synchrony and asynchrony between an epigenetic clock and developmental timing [450K array]

Project description:Genome wide DNA methylation profiling of human fetal retina samples. The Illumina Infinium DNA methylation Beadchip was used to obtain DNA methylation profiles in human fetal retina samples that were cultured in different ways. To better undrestand the relationship between developmental stage and epigenetic age (measured by the Horvath clock based on 353 CpGs as detailed in pubmed identifier: 24138928), we analyzed the highly regular sequence of developmental stage in the human neural retina. Findings: epigenetic age of fetal retina is highly correlated with chronological age. We find that epigenetic aging progresses normally in vitro. The correlation is retained in stem cell derived organoids but is accelerated in individuals with Down syndrome.

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Project description:Epigenetic changes have been used to estimate chronological age across the lifespan, and some studies suggest that epigenetic "aging" clocks may already operate in developing tissue. To better understand the relationship between developmental stage and epigenetic age, we utilized the highly regular sequence of development found in the mammalian neural retina and a well-established epigenetic aging clock based on DNA methylation. Our results demonstrate that the epigenetic age of fetal retina is highly correlated with chronological age. We further establish that epigenetic aging progresses normally in vitro, suggesting that epigenetic aging is a property of individual tissues. This correlation is also retained in stem cell-derived retinal organoids, but is accelerated in individuals with Down's syndrome, a progeroid-like condition. Overall, our results suggest that epigenetic aging begins as early as a few weeks post-conception, in fetal tissues, and the mechanisms underlying the phenomenon of epigenetic aging might be studied in developing organs.

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Project description:Human DNA methylation Beadchip v1.2 was used to analyze n=259 human saliva samples from Caucasians (non-Hispanic whites) and Hispanics collected from the PEG study (directed by Dr Beate Ritz). The main goal of the study was to measure the epigenetic age (also known as DNA methylation age) of saliva. To measure DNA methylation age, we used the epigenetic clock software described in Horvath S (n=2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928.

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