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Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming

Nature Aging volume 4, pages 14–26 (2024)Cite this article

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A Publisher Correction to this article was published on 04 January 2024

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Abstract

Over the past decade, there has been a dramatic increase in efforts to ameliorate aging and the diseases it causes, with transient expression of nuclear reprogramming factors recently emerging as an intriguing approach. Expression of these factors, either systemically or in a tissue-specific manner, has been shown to combat age-related deterioration in mouse and human model systems at the cellular, tissue and organismal level. Here we discuss the current state of epigenetic rejuvenation strategies via partial reprogramming in both mouse and human models. For each classical reprogramming factor, we provide a brief description of its contribution to reprogramming and discuss additional factors or chemical strategies. We discuss what is known regarding chromatin remodeling and the molecular dynamics underlying rejuvenation, and, finally, we consider strategies to improve the practical uses of epigenetic reprogramming to treat aging and age-related diseases, focusing on the open questions and remaining challenges in this emerging field.

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Fig. 1: Structural diagram of each reprogramming factor.
Fig. 2: Timeline highlighting publications on partial reprogramming in mouse and human models.
Fig. 3: Summary of detailed in vivo whole-organism partial reprogramming protocols.
Fig. 4: Summary of detailed in vitro partial reprogramming protocols in mouse and human.

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Acknowledgements

This work has been supported by: MCHRI, Woods Family Endowed Scholarship in Pediatric Translational Medicine (Stanford Maternal & Child Health Research Institute), the Breakthrough in Gerontology Award (BIG Award, AFAR/Glenn Foundation) and the Milky Way Research Foundation to V.S. By Paul F. Glenn Foundation for Medical Research and NIA/NIH grants R01AG019719 and R01DK100263 to D.A.S.

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Author notes

  1. These authors contributed equally: Andrea Cipriano, Mahdi Moqri, Sun Y. Maybury-Lewis.

Authors and Affiliations

  1. Department of Obstetrics & Gynecology, Stanford School of Medicine, Stanford University, Stanford, CA, USA

    Andrea Cipriano, Mahdi Moqri, Tineke Anna de Jong, Alexander Parker, Sajede Rasouli & Vittorio Sebastiano

  2. Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA

    Andrea Cipriano, Tineke Anna de Jong, Alexander Parker, Sajede Rasouli & Vittorio Sebastiano

  3. Department of Genetics, Stanford School of Medicine, Stanford University, Stanford, CA, USA

    Mahdi Moqri

  4. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Mahdi Moqri

  5. Department of Genetics, Harvard Medical School, Boston, MA, USA

    Sun Y. Maybury-Lewis, Ryan Rogers-Hammond & David A. Sinclair

  6. Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany

    Hans Robert Schöler

  7. Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA, USA

    David A. Sinclair

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  1. Andrea Cipriano
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Contributions

A.C., M.M. and V.S. designed and conceived the Review. The manuscript was written by A.C., M.M. and S.M.L. M.M. wrote the reprogramming factors section, S.M.L. the partial reprogramming event section and A.C. the partial reprogramming sections. T.A.J. contributed by writing the additional factor section. A.C. generated the figures, with help from S.R. R.R.H. provided a major contribution to the editing process with help from A.P. and S.R. H.R.S. provided suggestions and contributed on the reprogramming factor section. The Review was supervised and edited by V.S. and D.A.S.

Corresponding authors

Correspondence to David A. Sinclair or Vittorio Sebastiano.

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Competing interests

V.S. is a co-founder, SAB Chairman, Head of Research and shareholder of Turn Biotechnologies. D.A.S. is a consultant, inventor, board member and, in some cases, a founder and investor in Life Biosciences (a reprogramming company), EdenRock Sciences (Cantata, Metrobiotech), InsideTracker, Fully Aligned, Zymo, Galilei, Immetas, Animal Biosciences, Tally Health and others. For full information, see Supplementary File 1. The other authors declare no competing interests.

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Nature Aging thanks Maria Abad, Manuel Collado and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Cipriano, A., Moqri, M., Maybury-Lewis, S.Y. et al. Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming. Nat Aging 4, 14–26 (2024). https://doi.org/10.1038/s43587-023-00539-2

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