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The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Partial reprogramming induces a steady decline in epigenetic age before loss of somatic identity

Olova, Nelly, Simpson, Daniel J., Marioni, Riccardo E., Chandra, Tamir·2019·Aging Cell
DOI 10.1111/acel.12877PMC PMC6351826

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Abstract

Induced pluripotent stem cells (IPSCs), with their unlimited regenerative capacity, carry the promise for tissue replacement to counter age‐related decline. However, attempts to realize in vivo iPSC have invariably resulted in the formation of teratomas. Partial reprogramming in prematurely aged mice has shown promising results in alleviating age‐related symptoms without teratoma formation. Does partial reprogramming lead to rejuvenation (i.e., “younger” cells), rather than dedifferentiation, which bears the risk of cancer? Here, we analyse the dynamics of cellular age during human iPSC reprogramming and find that partial reprogramming leads to a reduction in the epigenetic age of cells. We also find that the loss of somatic gene expression and epigenetic age follows different kinetics, suggesting that they can be uncoupled and there could be a safe window where rejuvenation can be achieved with a minimized risk of cancer.

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  • Many aging-associated epigenetic marks are shed without the initiation of actual pluripotency programs.

    “many aging-associated epigenetic marks are shed without the initiation of actual pluripotency programs.”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [114]

    In Introduction, Results and Discussion (page not available), the paper reports that epigenetic age declines before full pluripotency, but says this decline occurs within the first wave of pluripotency gene expression. It also describes the early reprogramming phase as involving activation of pluripotency genes, contrary to the claim that the decline occurs without initiation of those programs. (LLM, conf=0.87)

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  • Pluripotency genes showed an inverse relationship that steadily increased over time until reaching an apparent threshold around day 15.

    “pluripotency genes showed an inverse relationship that steadily increased over time until reaching an apparent threshold around the same time.”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [114]

    In Results and Discussion (page unavailable), the paper reports that pluripotency-gene expression rose as epigenetic age declined. It does not report a shared threshold around day 15: the early gene cluster reached stable expression by day 20, and the late cluster by day 28. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Maintenance of somatic profiles makes cells more probable to revert toward the original and previously established cell fate when expression of reprogramming factors is stopped.

    “Maintenance of somatic profiles makes these cells more probable to revert toward the original and previously established cell fate when the expression of reprogramming factors is stopped.”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [114]

    In the Introduction, Results and Discussion, the paper says maintained fibroblast gene expression, together with increased senescence-gene expression, likely contributes to partially reprogrammed cells' high propensity to revert to a somatic phenotype. It separately reports that mouse fibroblasts revert when OSKM expression is discontinued. The claim presents maintenance alone as the cause of reversion after factors are stopped, which is stronger and more specific than the paper's account. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The time point around day 15 represents an optimal point for achieving epigenetic rejuvenation without losing cell identity.

    “These observations led to the conclusion that this time point represents an optimal point for achieving epigenetic rejuvenation without losing cell identity.”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [114]

    In Results and Discussion (page not provided), the paper reports a substantial decline in epigenetic age by day 15 while some fibroblast-specific genes still had high expression. It suggests a window for rejuvenation with partial maintenance of identity, but explicitly says its analysis cannot define precise safe boundaries. It therefore does not establish day 15 as an optimal point without loss of cell identity. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The reprogramming cassette induced a substantial reduction of DNA methylation age throughout the reprogramming process.

    “induced a substantial reduction of DNA methylation age throughout the reprogramming process, consistent with previous work using a different reprogramming system (Olova et al., 2019; Figure 1A).”

    From Multi-omic rejuvenation of human cells by maturation phase transient reprogramming (2022) · cites this paper as Olova et al., 2019

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Citations

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Metadata

Authors
Olova, N., Simpson, D. J., Marioni, R. E., & Chandra, T.
Affiliations
  • MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UK
  • Centre for Cognitive Ageing and Cognitive Epidemiology, Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine, University of Edinburgh Edinburgh UK
Venue
Aging Cell
Publisher
Wiley
Published
2018-11-18
Volume
18
Issue
1
ISSN
  • 1474-9718
  • 1474-9726
DOI
10.1111/acel.12877
PMC
PMC6351826
Cited by
190
References
9
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • University of Edinburgh
  • Biotechnology and Biological Sciences Research Council
  • Medical Research Council

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