Similar Datasets
Project description:Aging is reflected by genome-wide DNA methylation changes, but it is largely unclear how these epigenetic modifications are regulated. In this study, we explored the possibility to interfere with epigenetic clocks by epigenetic editing at individual CpG sites. CRISPR-guided approaches (dCas9-DNMT3A and CRISPRoff) facilitated targeted methylation at age-associated genomic regions that remained stable for up to three months. Furthermore, epigenetic editing evoked many genome-wide off-target effects, which were highly reproducible and enriched at other age-associated CpGs – thus, they are not random off-target effects but seem to resemble co-regulated epigenetic bystander modifications. 4C chromatin conformation analysis at age-associated sites revealed increased interactions with bystander modifications and other age-associated CpG sites. Subsequently, we multiplexed epigenetic modifications in HEK293T, mesenchymal stromal cells, and T cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While epigenetic editing at age-hypomethylated CpGs appeared less stable, it also resulted preferentially in bystander modifications at CpGs with highest correlation with chronological age. Notably, modifications were simultaneously observed at CpGs that gain and lose methylation with age. These results demonstrate that targeted epigenetic editing can modulate the epigenetic aging network in its entirety and thereby interfere with epigenetic clocks.
2025-02-11 | GSE285251 | GEO
Project description:Aging is reflected by genome-wide DNA methylation changes, but it is largely unclear how these epigenetic modifications are regulated. In this study, we explored the possibility to interfere with epigenetic clocks by epigenetic editing at individual CpG sites. CRISPR-guided approaches (dCas9-DNMT3A and CRISPRoff) facilitated targeted methylation at age-associated genomic regions that remained stable for up to three months. Furthermore, epigenetic editing evoked many genome-wide off-target effects, which were highly reproducible and enriched at other age-associated CpGs – thus, they are not random off-target effects but seem to resemble co-regulated epigenetic bystander modifications. 4C chromatin conformation analysis at age-associated sites revealed increased interactions with bystander modifications and other age-associated CpG sites. Subsequently, we multiplexed epigenetic modifications in HEK293T, mesenchymal stromal cells, and T cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While epigenetic editing at age-hypomethylated CpGs appeared less stable, it also resulted preferentially in bystander modifications at CpGs with highest correlation with chronological age. Notably, modifications were simultaneously observed at CpGs that gain and lose methylation with age. These results demonstrate that targeted epigenetic editing can modulate the epigenetic aging network in its entirety and thereby interfere with epigenetic clocks.
2025-02-11 | GSE285250 | GEO
Project description:Aging is reflected by genome-wide DNA methylation changes, but it is largely unclear how these epigenetic modifications are regulated. In this study, we explored the possibility to interfere with epigenetic clocks by epigenetic editing at individual CpG sites. CRISPR-guided approaches (dCas9-DNMT3A and CRISPRoff) facilitated targeted methylation at an age-associated genomic region in PDE4C that remained stable for more than three months. Furthermore, epigenetic editing evoked many genome-wide off-target effects, which were highly reproducible and enriched at other age-associated CpGs - thus, they are not random off-target effects, but seem to resemble coregulated epigenetic bystander modifications. 4C chromatin conformation analysis at age-associated sites revealed increased interactions with bystander modifications and other age-associated CpG sites. Subsequently, we multiplexed epigenetic modifications in HEK293T and primary T cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While epigenetic editing at age-hypomethylated CpGs appeared less stable, it also resulted in a clear enrichment of bystander modifications at other age-associated CpGs. Conversely, epigenetic clocks tend to be accelerated up to ten years after targeted DNA methylation, particularly at hypermethylated CpGs. These results demonstrate that targeted epigenome editing can modulate the epigenetic aging network in its entirety and thereby interfere with epigenetic clocks.
2025-02-11 | GSE269759 | GEO
Project description:Aging is reflected by genome-wide DNA methylation changes, but it is largely unclear how these epigenetic modifications are regulated. In this study, we explored the possibility to interfere with epigenetic clocks by epigenetic editing at individual CpG sites. CRISPR-guided approaches (dCas9-DNMT3A and CRISPRoff) facilitated targeted methylation at an age-associated genomic region in PDE4C that remained stable for more than three months. Furthermore, epigenetic editing evoked many genome-wide off-target effects, which were highly reproducible and enriched at other age-associated CpGs - thus, they are not random off-target effects, but seem to resemble coregulated epigenetic bystander modifications. 4C chromatin conformation analysis at age-associated sites revealed increased interactions with bystander modifications and other age-associated CpG sites. Subsequently, we multiplexed epigenetic modifications in HEK293T and primary T cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While epigenetic editing at age-hypomethylated CpGs appeared less stable, it also resulted in a clear enrichment of bystander modifications at other age-associated CpGs. Conversely, epigenetic clocks tend to be accelerated up to ten years after targeted DNA methylation, particularly at hypermethylated CpGs. These results demonstrate that targeted epigenome editing can modulate the epigenetic aging network in its entirety and thereby interfere with epigenetic clocks.
2025-02-11 | GSE269650 | GEO
Project description:Aging is reflected by genome-wide DNA methylation changes, but it is largely unclear how these epigenetic modifications are regulated. In this study, we explored the possibility to interfere with epigenetic clocks by epigenetic editing at individual CpG sites. CRISPR-guided approaches (dCas9-DNMT3A and CRISPRoff) facilitated targeted methylation at an age-associated genomic region in PDE4C that remained stable for more than three months. Furthermore, epigenetic editing evoked many genome-wide off-target effects, which were highly reproducible and enriched at other age-associated CpGs - thus, they are not random off-target effects, but seem to resemble coregulated epigenetic bystander modifications. 4C chromatin conformation analysis at age-associated sites revealed increased interactions with bystander modifications and other age-associated CpG sites. Subsequently, we multiplexed epigenetic modifications in HEK293T and primary T cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While epigenetic editing at age-hypomethylated CpGs appeared less stable, it also resulted in a clear enrichment of bystander modifications at other age-associated CpGs. Conversely, epigenetic clocks tend to be accelerated up to ten years after targeted DNA methylation, particularly at hypermethylated CpGs. These results demonstrate that targeted epigenome editing can modulate the epigenetic aging network in its entirety and thereby interfere with epigenetic clocks.
2025-02-11 | GSE269758 | GEO
Project description:Aging is reflected by genome-wide DNA methylation changes, but it is largely unclear how these epigenetic modifications are regulated. In this study, we explored the possibility to interfere with epigenetic clocks by epigenetic editing at individual CpG sites. CRISPR-guided approaches (dCas9-DNMT3A and CRISPRoff) facilitated targeted methylation at an age-associated genomic region in PDE4C that remained stable for more than three months. Furthermore, epigenetic editing evoked many genome-wide off-target effects, which were highly reproducible and enriched at other age-associated CpGs - thus, they are not random off-target effects, but seem to resemble coregulated epigenetic bystander modifications. 4C chromatin conformation analysis at age-associated sites revealed increased interactions with bystander modifications and other age-associated CpG sites. Subsequently, we multiplexed epigenetic modifications in HEK293T and primary T cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While epigenetic editing at age-hypomethylated CpGs appeared less stable, it also resulted in a clear enrichment of bystander modifications at other age-associated CpGs. Conversely, epigenetic clocks tend to be accelerated up to ten years after targeted DNA methylation, particularly at hypermethylated CpGs. These results demonstrate that targeted epigenome editing can modulate the epigenetic aging network in its entirety and thereby interfere with epigenetic clocks.
2025-02-11 | GSE269757 | GEO
Project description:Aging is reflected by genome-wide DNA methylation changes, but it is largely unclear how these epigenetic modifications are regulated. In this study, we explored the possibility to interfere with epigenetic clocks by epigenetic editing at individual CpG sites. CRISPR-guided approaches (dCas9-DNMT3A and CRISPRoff) facilitated targeted methylation at an age-associated genomic region in PDE4C that remained stable for more than three months. Furthermore, epigenetic editing evoked many genome-wide off-target effects, which were highly reproducible and enriched at other age-associated CpGs - thus, they are not random off-target effects, but seem to resemble coregulated epigenetic bystander modifications. 4C chromatin conformation analysis at age-associated sites revealed increased interactions with bystander modifications and other age-associated CpG sites. Subsequently, we multiplexed epigenetic modifications in HEK293T and primary T cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While epigenetic editing at age-hypomethylated CpGs appeared less stable, it also resulted in a clear enrichment of bystander modifications at other age-associated CpGs. Conversely, epigenetic clocks tend to be accelerated up to ten years after targeted DNA methylation, particularly at hypermethylated CpGs. These results demonstrate that targeted epigenome editing can modulate the epigenetic aging network in its entirety and thereby interfere with epigenetic clocks.
2025-02-11 | GSE269756 | GEO
Project description:Aging is reflected by genome-wide DNA methylation changes, but it is largely unclear how these epigenetic modifications are regulated. In this study, we explored the possibility to interfere with epigenetic clocks by epigenetic editing at individual CpG sites. CRISPR-guided approaches (dCas9-DNMT3A and CRISPRoff) facilitated targeted methylation at an age-associated genomic region in PDE4C that remained stable for more than three months. Furthermore, epigenetic editing evoked many genome-wide off-target effects, which were highly reproducible and enriched at other age-associated CpGs - thus, they are not random off-target effects, but seem to resemble coregulated epigenetic bystander modifications. 4C chromatin conformation analysis at age-associated sites revealed increased interactions with bystander modifications and other age-associated CpG sites. Subsequently, we multiplexed epigenetic modifications in HEK293T and primary T cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While epigenetic editing at age-hypomethylated CpGs appeared less stable, it also resulted in a clear enrichment of bystander modifications at other age-associated CpGs. Conversely, epigenetic clocks tend to be accelerated up to ten years after targeted DNA methylation, particularly at hypermethylated CpGs. These results demonstrate that targeted epigenome editing can modulate the epigenetic aging network in its entirety and thereby interfere with epigenetic clocks.
2025-02-11 | GSE269755 | GEO
Project description:Aging is reflected by genome-wide DNA methylation changes, but it is largely unclear how these epigenetic modifications are regulated. In this study, we explored the possibility to interfere with epigenetic clocks by epigenetic editing at individual CpG sites. CRISPR-guided approaches (dCas9-DNMT3A and CRISPRoff) facilitated targeted methylation at age-associated genomic regions that remained stable for up to three months. Furthermore, epigenetic editing evoked many genome-wide off-target effects, which were highly reproducible and enriched at other age-associated CpGs – thus, they are not random off-target effects but seem to resemble co-regulated epigenetic bystander modifications. 4C chromatin conformation analysis at age-associated sites revealed increased interactions with bystander modifications and other age-associated CpG sites. Subsequently, we multiplexed epigenetic modifications in HEK293T, mesenchymal stromal cells, and T cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While epigenetic editing at age-hypomethylated CpGs appeared less stable, it also resulted preferentially in bystander modifications at CpGs with highest correlation with chronological age. Notably, modifications were simultaneously observed at CpGs that gain and lose methylation with age. These results demonstrate that targeted epigenetic editing can modulate the epigenetic aging network in its entirety and thereby interfere with epigenetic clocks.
2025-02-11 | GSE285252 | GEO
Project description:Aging is reflected by genome-wide DNA methylation changes, but it is largely unclear how these epigenetic modifications are regulated. In this study, we explored the possibility to interfere with epigenetic clocks by epigenetic editing at individual CpG sites. CRISPR-guided approaches (dCas9-DNMT3A and CRISPRoff) facilitated targeted methylation at an age-associated genomic region in PDE4C that remained stable for more than three months. Furthermore, epigenetic editing evoked many genome-wide off-target effects, which were highly reproducible and enriched at other age-associated CpGs - thus, they are not random off-target effects, but seem to resemble coregulated epigenetic bystander modifications. 4C chromatin conformation analysis at age-associated sites revealed increased interactions with bystander modifications and other age-associated CpG sites. Subsequently, we multiplexed epigenetic modifications in HEK293T and primary T cells at five genomic regions that become either hypermethylated or hypomethylated upon aging. While epigenetic editing at age-hypomethylated CpGs appeared less stable, it also resulted in a clear enrichment of bystander modifications at other age-associated CpGs. Conversely, epigenetic clocks tend to be accelerated up to ten years after targeted DNA methylation, particularly at hypermethylated CpGs. These results demonstrate that targeted epigenome editing can modulate the epigenetic aging network in its entirety and thereby interfere with epigenetic clocks.
2025-02-11 | GSE269753 | GEO