Cross-Tissue Comparison of Epigenetic Aging Clocks in Humans
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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: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
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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:Organisms have adapted to the changing environmental conditions within the 24h cycle of the day by temporally segregating tissue physiology to the optimal time of the day. On the cellular level temporal segregation of physiological processes is established by the circadian clock, a Bmal1 dependent transcriptional oscillator network. The circadian clocks within individual cells of a tissue are synchronised by environmental signals, mainly light, in order to reach temporally segregated physiology on the tissue level. However, how light mediated synchronisation of peripheral tissue clocks is achieved mechanistically and whether circadian clocks in different organs are autonomous or interact with each other to achieve rhythmicity is unknown. Here we report that light can synchronise core circadian clocks in two peripheral tissues, the epidermis and liver hepatocytes, even in the complete absence of functional clocks in any other tissue within the whole organism. On the other hand, tissue extrinsic circadian clock rhythmicity is necessary to retain rhythmicity of the epidermal clock in the absence of light, proving for the first time that the circadian clockwork acts as a memory of time for the synchronisation of peripheral clocks in the absence of external entrainment signals. Furthermore, we find that tissue intrinsic Bmal1 is an important regulator of the epidermal differentiation process whose deregulation leads to a premature aging like phenotype of the epidermis. Thus, our results establish a new model for the segregation of peripheral tissue physiology whereby the synchronisation of peripheral clocks is acquired by the interaction of a light dependent but circadian clock independent pathway with circadian clockwork dependent cues.
2019-03-25 | GSE115104 | GEO
Project description:We used two RNA samples that differed only by a set of three hemoglobin transcripts to compare microarray cross-hybridization between two target preparation protocols. We found widespread cross-hybridization using standard cRNA target but substantially less cross-hybridization using cDNA target. Keywords: protocol comparison
2006-09-08 | GSE4532 | GEO
Project description:The brain of the tree shrew (Tupaia belangeri chinensis, TS) has drawn considerable attention due to its high similarities to that of humans. The hippocampal formation is one of the main brain regions affected in aging and neurological diseases. However, the cellular compositions of the TS hippocampus involving in aging development remain elusive. Here we established the first single-nucleus transcriptomic profiles of TS hippocampus and identified 16 cell subpopulations. The cross-species comparison of multi-species hippocampus revealed the cell landscape and associated specific gene expression patterns at the single-cell resolution. We validated ROBO2 and FGF14 as a TS/primate-specific NB[1] marker and confirmed TS-specific neural stem cells (NSCs) with SOX5/SOX6 high expression. Then, we identified TS cell types and molecular pathways closely associated with human neurological disorders, bridging the gap between gene mutations and pathogenesis. Importantly, we established the first single-nucleus transcriptomic atlas of TS hippocampal aging, in which the dynamics of the neurogenic lineage and the diversity of oligodendrocyte and microglia was revealed and delineated. Specifically, the regulatory continuum from adult NSCs to immature and mature granule cells was addressed in the neurogenic lineage. Meanwhile, in-depth dissection of gene-expression dynamics revealed impaired neurogenesis along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and endothelial cells may contribute to a hostile microenvironment for neurogenesis. Together, to our knowledge, this is the first time to report a single-cell atlas of TS in hippocampus aging which therefore provides extensive resources in both cell compositions and specific gene map for future research regarding neural science, evolutionary developmental biology, and regenerative medicine, combined with a comprehensive analysis across species.
2025-03-12 | GSE229035 | GEO
Project description:Organisms have adapted to the changing environmental conditions within the 24h cycle of the day by temporally segregating tissue physiology to the optimal time of the day. On the cellular level temporal segregation of physiological processes is established by the circadian clock, a Bmal1 dependent transcriptional oscillator network. The circadian clocks within individual cells of a tissue are synchronised by environmental signals, mainly light, in order to reach temporally segregated physiology on the tissue level. However, how light mediated synchronisation of peripheral tissue clocks is achieved mechanistically and whether circadian clocks in different organs are autonomous or interact with each other to achieve rhythmicity is unknown. Here we report that light can synchronise core circadian clocks in two peripheral tissues, the epidermis and liver hepatocytes, even in the complete absence of functional clocks in any other tissue within the whole organism. On the other hand, tissue extrinsic circadian clock rhythmicity is necessary to retain rhythmicity of the epidermal clock in the absence of light, proving for the first time that the circadian clockwork acts as a memory of time for the synchronisation of peripheral clocks in the absence of external entrainment signals. Furthermore, we find that tissue intrinsic Bmal1 is an important regulator of the epidermal differentiation process whose deregulation leads to a premature aging like phenotype of the epidermis. Thus, our results establish a new model for the segregation of peripheral tissue physiology whereby the synchronisation of peripheral clocks is acquired by the interaction of a light dependent but circadian clock independent pathway with circadian clockwork dependent cues.
2019-03-25 | GSE114943 | GEO
Project description:Cross-tissue immune cell analysis reveals tissue-specific features in humans
| PRJEB51634 | ENA