Cross-Tissue Comparison of Epigenetic Aging Clocks in Humans
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ABSTRACT:
PROVIDER: PRJNA1178652 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetic clocks are a common group of tools used to measure biological aging – the progressive deterioration of cells, tissues and organs. Epigenetic clocks have been trained almost exclusively using blood-based tissues but there is growing interest in estimating epigenetic age using less-invasive oral-based tissues (i.e., buccal or saliva) in both research and commercial settings. However, differentiated cell types across body tissues exhibit unique DNA methylation landscapes and age-related alterations to the DNA methylome. Applying epigenetic clocks derived from blood-based tissues to estimate epigenetic age of oral-based tissues may introduce biases. We tested the within-person comparability of common epigenetic clocks across four tissue types: buccal epithelial, saliva, dry blood spots, and peripheral blood mononuclear cells. We tested 163 distinct tissue samples from 47 individuals aged 19-70 years. Overall, there were significant within-person differences in epigenetic clock estimates from oral-based versus blood-based tissues, with average differences of almost 30 years observed in some age clocks. In addition, most epigenetic clock estimates of blood-based tissues exhibited low correlation with estimates from oral-based tissues despite controlling for cellular proportions and other technical factors. Notably, the Skin and Blood clock exhibited the lowest age acceleration values of any clock across all tissue types, indicating its unique ability to accurately estimate chronological age in both oral- and blood-based tissues. Our findings indicate that application of blood-derived epigenetic clocks in oral-based tissues may not yield comparable estimates of epigenetic age, highlighting the need for careful consideration of tissue type when estimating epigenetic age. NOTE: The full study included children and adult samples, however, the current data only includes the adult samples (sample sizes and age range have been adjusted to reflect the adult data only).
2025-02-07 | GSE280465 | GEO
Project description:The notion that germline does not age goes back to the 19th century ideas of August Weismann. However, being in a metabolically active state, germline accumulates damage and other age-related changes over time, i.e., they age. For new life to begin in the same young state, they must be rejuvenated in the offspring. Here, we developed a new multi-tissue epigenetic clock and applied it, together with other aging clocks, to track changes in biological age during mouse and human prenatal development. This analysis revealed a significant decrease in biological age, i.e. rejuvenation, during early stages of embryogenesis, followed by an increase in later stages. We further found that pluripotent stem cells do not age even after extensive passaging and that the examined epigenetic age dynamics is conserved across species. Overall, this study uncovers a natural rejuvenation event during embryogenesis and suggests that the minimal biological age (the ground zero) marks the beginning of organismal aging.
2021-05-10 | GSE171332 | GEO
Project description:We carried out blood transcriptome-wide association studies and replicated results to identify genes whose expression differs across the human aging spectrum. The transcriptional landscape of aging in humans
2014-06-15 | E-GEOD-58137 | biostudies-arrayexpress
Project description:Chronological aging correlates with epigenetic modifications at specific loci, calibrated to species lifespan. Such ‘epigenetic clocks’ appear conserved among mammals, but whether they are cell-autonomous and restricted by maximal organismal lifespan remains unknown. We used a multi-lifetime murine model of repeat vaccination and memory T cell transplantation to test whether epigenetic aging tracks with cellular replication, and if such clocks continue ‘counting’ beyond species lifespan. We found that memory T cell epigenetic clocks tick independently of host age and continue through four lifetimes. Instead of recording chronological time, T cells recorded proliferative experience through modification of cell cycle regulatory genes. Applying this epigenetic profile across a range of human T cell contexts, we found that naïve T cells appeared ‘young’ regardless of organism age, while in pediatric patients, T-cell acute lymphoblastic leukemia (T-ALL) appeared to have epigenetically aged for up to 200 years. Thus, T cell epigenetic clocks measure replicative history and can continue to accumulate well-beyond organismal lifespan.
2024-05-06 | GSE263941 | GEO
Project description:Identification of the key epigenetic determinants of chondrocyte aging in humans
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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 | 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 | 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 | GSE269759 | GEO