Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE171332 | GEO | 2021/05/10
REPOSITORIES: GEO
Similar Datasets
Project description:Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been proposed. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. We studied the transcriptional changes in young, aged and mechanically rejuvenated fibroblasts using RNA-seq. The mechanically rejuvenated aged fibroblasts, that had reset their transcription to a younger cell state. In addition, the rejuvenated cells contractile properties were maintained over multiple cell passages. Taken together, our results provide a multi-scale characterization of the chromatin reorganization that accompanies cellular aging and rejuvenation.
2024-03-20 | GSE237269 | GEO
Project description:Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been proposed. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. We studied the transcriptional and genome-wide chromatin organization changes in young, aged and mechanically rejuvenated fibroblasts using RNA-seq and Hi-C experiments. The mechanically rejuvenated aged fibroblasts, that had reset their transcription to a younger cell state, showed a reorganization of the inter-chromosomal contacts and lamina-associated domains. Interestingly, the observed chromatin reorganization correlated with the transcriptional changes. Immunofluorescence experiments in the rejuvenated state confirmed increased contractility and reduced chromosome copy number variations, similar to younger fibroblasts. In addition, the rejuvenated contractile properties were maintained over multiple cell passages. Taken together, our results provide a multi-scale characterization of the chromatin reorganization that accompanies cellular aging and rejuvenation.
2024-03-20 | GSE237268 | GEO
Project description:Ageing is the gradual decline in organismal fitness that occurs over time leading to tissue dysfunction and disease. At the cellular level, ageing is associated with reduced function, altered gene expression and a perturbed epigenome. Somatic cell reprogramming, the process of converting somatic cells to induced pluripotent stem cells (iPSCs), can reverse these age-associated changes. However, during iPSC reprogramming somatic cell identity is lost, and can be difficult to reacquire as re-differentiated iPSCs often resemble foetal rather than mature adult cells. Recent work has demonstrated that the epigenome is already rejuvenated by the maturation phase of reprogramming, which suggests full iPSC reprogramming is not required to reverse ageing of somatic cells. Here we have developed the first “maturation phase transient reprogramming” (MPTR) method, where reprogramming factors are expressed until this rejuvenation point followed by withdrawal of their induction. Using dermal fibroblasts from middle age donors, we found that cells reacquire their fibroblast identity following MPTR, possibly as a result of persisting epigenetic memory at enhancers. Excitingly, our method substantially rejuvenated multiple cellular attributes including the transcriptome, which was rejuvenated by around 30 years as measured by a novel transcriptome clock. The epigenome, including H3K9me3 histone methylation levels and the DNA methylation ageing clock, was rejuvenated to a similar extent. MPTR fibroblasts produced youthful levels of collagen proteins, suggesting functional rejuvenation. Overall, our work demonstrates that it is possible to separate rejuvenation from pluripotency reprogramming, which should facilitate the discovery of novel anti-ageing genes and therapies.
2022-04-19 | GSE165179 | GEO
Project description:Ageing is the gradual decline in organismal fitness that occurs over time leading to tissue dysfunction and disease. At the cellular level, ageing is associated with reduced function, altered gene expression and a perturbed epigenome. Somatic cell reprogramming, the process of converting somatic cells to induced pluripotent stem cells (iPSCs), can reverse these age-associated changes. However, during iPSC reprogramming somatic cell identity is lost, and can be difficult to reacquire as re-differentiated iPSCs often resemble foetal rather than mature adult cells. Recent work has demonstrated that the epigenome is already rejuvenated by the maturation phase of reprogramming, which suggests full iPSC reprogramming is not required to reverse ageing of somatic cells. Here we have developed the first “maturation phase transient reprogramming” (MPTR) method, where reprogramming factors are expressed until this rejuvenation point followed by withdrawal of their induction. Using dermal fibroblasts from middle age donors, we found that cells reacquire their fibroblast identity following MPTR, possibly as a result of persisting epigenetic memory at enhancers. Excitingly, our method substantially rejuvenated multiple cellular attributes including the transcriptome, which was rejuvenated by around 30 years as measured by a novel transcriptome clock. The epigenome, including H3K9me3 histone methylation levels and the DNA methylation ageing clock, was rejuvenated to a similar extent. MPTR fibroblasts produced youthful levels of collagen proteins, suggesting functional rejuvenation. Overall, our work demonstrates that it is possible to separate rejuvenation from pluripotency reprogramming, which should facilitate the discovery of novel anti-ageing genes and therapies.
2022-04-19 | GSE165178 | GEO
Project description:Ageing is the gradual decline in organismal fitness that occurs over time leading to tissue dysfunction and disease. At the cellular level, ageing is associated with reduced function, altered gene expression and a perturbed epigenome. Somatic cell reprogramming, the process of converting somatic cells to induced pluripotent stem cells (iPSCs), can reverse these age-associated changes. However, during iPSC reprogramming somatic cell identity is lost, and can be difficult to reacquire as re-differentiated iPSCs often resemble foetal rather than mature adult cells. Recent work has demonstrated that the epigenome is already rejuvenated by the maturation phase of reprogramming, which suggests full iPSC reprogramming is not required to reverse ageing of somatic cells. Here we have developed the first “maturation phase transient reprogramming” (MPTR) method, where reprogramming factors are expressed until this rejuvenation point followed by withdrawal of their induction. Using dermal fibroblasts from middle age donors, we found that cells reacquire their fibroblast identity following MPTR, possibly as a result of persisting epigenetic memory at enhancers. Excitingly, our method substantially rejuvenated multiple cellular attributes including the transcriptome, which was rejuvenated by around 30 years as measured by a novel transcriptome clock. The epigenome, including H3K9me3 histone methylation levels and the DNA methylation ageing clock, was rejuvenated to a similar extent. MPTR fibroblasts produced youthful levels of collagen proteins, suggesting functional rejuvenation. Overall, our work demonstrates that it is possible to separate rejuvenation from pluripotency reprogramming, which should facilitate the discovery of novel anti-ageing genes and therapies.
2022-04-19 | GSE165177 | GEO
Project description:Ageing is the gradual decline in organismal fitness that occurs over time leading to tissue dysfunction and disease. At the cellular level, ageing is associated with reduced function, altered gene expression and a perturbed epigenome. Somatic cell reprogramming, the process of converting somatic cells to induced pluripotent stem cells (iPSCs), can reverse these age-associated changes. However, during iPSC reprogramming somatic cell identity is lost, and can be difficult to reacquire as re-differentiated iPSCs often resemble foetal rather than mature adult cells. Recent work has demonstrated that the epigenome is already rejuvenated by the maturation phase of reprogramming, which suggests full iPSC reprogramming is not required to reverse ageing of somatic cells. Here we have developed the first “maturation phase transient reprogramming” (MPTR) method, where reprogramming factors are expressed until this rejuvenation point followed by withdrawal of their induction. Using dermal fibroblasts from middle age donors, we found that cells reacquire their fibroblast identity following MPTR, possibly as a result of persisting epigenetic memory at enhancers. Excitingly, our method substantially rejuvenated multiple cellular attributes including the transcriptome, which was rejuvenated by around 30 years as measured by a novel transcriptome clock. The epigenome, including H3K9me3 histone methylation levels and the DNA methylation ageing clock, was rejuvenated to a similar extent. MPTR fibroblasts produced youthful levels of collagen proteins, suggesting functional rejuvenation. Overall, our work demonstrates that it is possible to separate rejuvenation from pluripotency reprogramming, which should facilitate the discovery of novel anti-ageing genes and therapies.
2022-04-19 | GSE165176 | GEO
Project description:Molecular mechanisms of organismal and cell aging remain incompletely understood. We, therefore, generated a body-wide map of noncoding RNA (ncRNA) expression in aging (16 organs at ten timepoints from 1 to 27 months) and rejuvenated mice. We found molecular aging trajectories are largely tissue-specific except for eight broadly deregulated microRNAs (miRNAs). Their individual abundance mirrors their presence in circulating plasma and extracellular vesicles (EVs) whereas tissue-specific ncRNAs were less present. For miR-29c-3p, we observe the largest correlation with aging in solid organs, plasma and EVs. In mice rejuvenated by heterochronic parabiosis, miR-29c-3p was the most prominent miRNA restored to similar levels found in young liver. miR-29c-3p targets the extracellular matrix and secretion pathways, known to be implicated in aging. We provide a map of organism-wide expression of ncRNAs with aging and rejuvenation and identify a set of broadly deregulated miRNAs, which may function as systemic regulators of aging via plasma and EVs.
2023-03-10 | GSE217458 | GEO
Project description:Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply deep sequencing of RNA 3' ends ("3-seq") to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed "skin aging") and the impact of broadband light (BBL) treatment. We find that skin aging was associated with the significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became "rejuvenated" after BBL treatment, i.e. more similar in expression level of youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long non-coding RNAs. Skin aging is not associated with systematic changes in 3' end mRNA processing. Hence, BBL treatment can restore the gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveals a novel set of targets that may lead to new insights into the human skin aging process. Examination of broadband light treated and untreated human skin transcriptomes of 5 women aged 50 years or more. They were compared to the skin transcriptomes of 5 young women aged 30 years or less.
2012-07-30 | E-GEOD-39170 | biostudies-arrayexpress
Project description:Aging of hematopoietic stem cells (HSCs) is associated with the decline of their regenerative capacity, and multi-lineage differentiation potential, contributing to development of blood disorders. The bone marrow microenvironment was recently suggested to influence HSC aging, however the underlying mechanisms remain largely unknown. Here, we show that HSC aging critically depends on bone marrow innervation by the sympathetic nervous system (SNS), as premature loss of SNS nerves or adrenoreceptor b3 (ADRb3) signaling in the microenvironment accelerated the appearance of HSC aging phenotypes reminiscent of physiological aging. Strikingly, supplementation of ADRb3 sympathomimetics to old mice significantly rejuvenated in vivo function of old HSCs, suggesting that the preservation or restitution of SNS innervation during aging may hold the potential for novel HSC rejuvenation strategies.
2018-05-01 | GSE109546 | GEO
Project description:Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply deep sequencing of RNA 3' ends ("3-seq") to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed "skin aging") and the impact of broadband light (BBL) treatment. We find that skin aging was associated with the significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became "rejuvenated" after BBL treatment, i.e. more similar in expression level of youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long non-coding RNAs. Skin aging is not associated with systematic changes in 3' end mRNA processing. Hence, BBL treatment can restore the gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveals a novel set of targets that may lead to new insights into the human skin aging process.
2012-07-30 | GSE39170 | GEO