Evidence map›Paper›PMID 35390271›Full record

ArticleeLife2022

Multi-omic rejuvenation of human cells by maturation phase transient reprogramming.

Diljeet Gill, Aled Parry, Fátima Santos, Hanneke Okkenhaug, Christopher D Todd, Irene Hernando-Herraez, Thomas M Stubbs, Inês Milagre, Wolf Reik

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed
12.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

106 citing papers in PubMed, 167 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
  6. Review
  7. Evolutionary genetics of ageing.Nature reviews. Genetics · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. A cross-talk between p16High senescence and cellular reprogramming.Clinical science (London, England : 1979) · 2026
    Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article

46 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Diljeet GillEpigenetics Programme, Babraham Institute, Cambridge, United Kingdom.ORCID 0000-0002-5725-2466
Aled ParryEpigenetics Programme, Babraham Institute, Cambridge, United Kingdom.ORCID 0000-0001-5192-3727
Fátima SantosEpigenetics Programme, Babraham Institute, Cambridge, United Kingdom.ORCID 0000-0002-3854-4084
Hanneke OkkenhaugImaging Facility, Babraham Institute, Cambridge, United Kingdom.ORCID 0000-0003-0669-4069
Christopher D ToddEpigenetics Programme, Babraham Institute, Cambridge, United Kingdom.ORCID 0000-0003-2663-6173
Irene Hernando-HerraezEpigenetics Programme, Babraham Institute, Cambridge, United Kingdom.ORCID 0000-0003-1193-8419
Thomas M StubbsChronomics Limited, London, United Kingdom.ORCID 0000-0002-2990-7381
Inês MilagreLaboratory for Epigenetic Mechanisms/Chromosome Dynamics Lab, Instituto Gulbenkian de Ciência, Oeiras, Portugal.ORCID 0000-0003-4753-5523
Wolf ReikEpigenetics Programme, Babraham Institute, Cambridge, United Kingdom.ORCID 0000-0003-0216-9881
Babraham Institute · GBInstituto Gulbenkian de Ciência · PT

Funding

Biotechnology and Biological Sciences Research CouncilWellcome Trust 210754/Z/18/ZWellcome Trust 215912/Z/19/Z
6 · The paper itself

Abstract

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. Recent work has demonstrated that the epigenome is already rejuvenated by the maturation phase of somatic cell reprogramming, which suggests full 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 selectively expressed until this rejuvenation point then withdrawn. Applying MPTR to dermal fibroblasts from middle-aged donors, we found that cells temporarily lose and then reacquire their fibroblast identity, possibly as a result of epigenetic memory at enhancers and/or persistent expression of some fibroblast genes. 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 was rejuvenated to a similar extent, including H3K9me3 levels and the DNA methylation ageing clock. The magnitude of rejuvenation instigated by MPTR appears substantially greater than that achieved in previous transient reprogramming protocols. In addition, MPTR fibroblasts produced youthful levels of collagen proteins, and showed partial functional rejuvenation of their migration speed. Finally, our work suggests that optimal time windows exist for rejuvenating the transcriptome and the epigenome. Overall, we demonstrate that it is possible to separate rejuvenation from complete pluripotency reprogramming, which should facilitate the discovery of novel anti-ageing genes and therapies.

Indexed as

Induced Pluripotent Stem CellsRejuvenationCellular ReprogrammingDNA MethylationEpigenomeEpigenomicsFibroblastsHumansMiddle AgedageingDNA methylationgeneticsgenomicshumanregenerative medicinerejuvenationreprogrammingstem cellstranscription

Identifiers

PMID35390271
PMCPMC9023058
OpenAlexW4225567851

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.