Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA389099 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Osteoporosis is an age-related metabolic bone disease. Hence, osteoporotic patients might suffer from molecular features of accelerated aging, which is generally reflected by specific age-associated DNA methylation (DNAm) changes. In this study, we analyzed genome wide DNAm profiles of peripheral blood from patients with manifest primary osteoporosis and non-osteoporotic controls. Statistical analysis did not reveal any individual CG dinucleotides (CpG sites) with significant aberrant DNAm in osteoporosis. Subsequently, we analyzed if age-associated DNAm patterns are increased in OP. Using three independent age-predictors we did not find any evidence for accelerated epigenetic age in blood of osteoporotic patients. Taken together, osteoporosis is not reflected by characteristic DNAm patterns of peripheral blood that might be used as biomarker for the disease. The prevalence of osteoporosis is age-associated – but it is not associated with premature epigenetic aging in peripheral blood.
2018-03-13 | GSE99624 | 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 | 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 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 | GSE269754 | 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 | 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 | GSE269753 | 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:Epigenetic clocks can quantify DNA methylation by measuring the methylation levels at specific sites in the genome, which correlate with biological age (BA). Accelerated aging, where BA exceeds chronological age (CA), has been studied in relation to cancer development, but its utility in cancer prevention remains unclear. Accelerated aging holds promise as a tool to explain the rise in early onset colorectal cancer (EOCRC). We investigate the association of accelerated aging and the presence of pre-neoplastic polyps (PNP) in the colon, defined as tubular adenomas and sessile serrated adenomas. In this study of persons under age 50 undergoing colonoscopy, we used peripheral blood samples to determine BA and age acceleration metrics. Age acceleration was determined by interrogating DNA methylation (DNAm) at specific CpG sites across the genome, which has been shown to correlate with age. We then conducted logistic regression analyses to evaluate the association between age acceleration and PNPs. In total, 51 patient samples were evaluated. We found that that the odds of harboring a PNP are 17% higher with 1 year of accelerated aging, as measured by GrimAge. However, the strongest risk factor for PNPs remained male sex. This represents one of the first studies to explore accelerated aging and PNP in patients under the age of 50. A risk-stratified approach to EOCRC screening would minimize unnecessary colonoscopies and minimize healthcare burden while addressing the rise in EOCRC. Our findings suggest that BA calculations with peripheral blood collections could be an important component of such a risk model.
2024-12-11 | GSE282666 | GEO