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: Not available
| S-EPMC11984668 | biostudies-literature
Project description:Aging is the primary risk factor for most neurodegenerative diseases, yet the cell-type-specific progression of brain aging remains poorly understood. Here, human cell-type-specific transcriptomic aging clocks are developed using high-quality single-nucleus RNA sequencing data from post mortem human prefrontal cortex tissue of 31 donors aged 18–94 years, encompassing 73,941 high-quality nuclei. Distinct transcriptomic changes are observed across major cell types, including upregulation of inflammatory response genes in microglia from older samples. Aging clocks trained on each major cell type accurately predict chronological age, capture biologically relevant pathways, and remain robust in independent single-nucleus RNA-sequencing datasets, underscoring their broad applicability. Notably, cell-type-specific age acceleration is identified in individuals with Alzheimer's disease and schizophrenia, suggesting altered aging trajectories in these conditions. These findings demonstrate the feasibility of cell-type-specific transcriptomic clocks to measure biological aging in the human brain and highlight potential mechanisms of selective vulnerability in neurodegenerative diseases.
2025-08-29 | GSE291605 | 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:By analyzing ChIP-seq data across six tissues and six histone marks, we developed 36 tissue-specific histone modification-based epigenetic clocks that detect age acceleration in leukemia and reversal following treatment. Many age-associated loci showed nonlinear trajectories peaking at midlife, and super-enhancer fragmentation was observed with age. Functional validation of an H3K27ac peak near IGF2BP3 confirmed its role in senescence via TRA2A regulation. These clocks also generalized to Drosophila melanogaster, highlighting the evolutionary conservation and utility of histone modifications as aging biomarkers.
2026-02-24 | GSE296812 | GEO
Project description:Cross species comparison of expression patterns
| PRJNA91829 | ENA
Project description:Human Brain Cell-Type-Specific Aging Clocks Based on Single-Nuclei Transcriptomics
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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:Histone modification clocks for robust cross-species biological age prediction and elucidating senescence regulation
| PRJNA1261086 | ENA