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SENESCENCE

Apolipoprotein E regulates chromatin stability and senescence

Nature Aging volume 2, pages 282–284 (2022)Cite this article

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Apolipoprotein E (APOE) is an important regulator of lipid metabolism and is genetically associated with longevity and age-related diseases such as Alzheimer’s disease. However, the molecular mechanisms that link APOE and aging are incompletely understood. Now an article in Nature Aging reveals that nuclear APOE promotes senescence by destabilizing heterochromatin.

The authors begin by investigating human mesenchymal progenitor cells (MPCs), which can differentiate into several cell types such as osteoblasts, chondrocytes and adipocytes. The proliferation of these cells has a limit (as is the case for all somatic cells), commonly known as the ‘Hayflick limit’. After serial passages, the proliferation of the cells halts, and they enter a state termed senescence — a stable form of cell-cycle arrest associated with a proinflammatory secretory phenotype. Senescence of MPCs is coupled with stem and progenitor cell exhaustion, leading to impaired tissue renewal and repair during aging4. Further, because mesenchymal stem and progenitor cells (MSPCs) can migrate to injured tissues to facilitate tissue repair, they are considered as an attractive tool for regenerative medicine5. However, MSPCs from older individuals show reduced regenerative abilities, thus limiting their therapeutic benefits. Therefore, it is critical to understand how MSPC senescence is regulated.

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Fig. 1: APOE promotes MPC senescence through disrupting heterochromatin.

References

  1. Mahley, R. W. & Rall, S. C. Jr Annu. Rev. Genomics Hum. Genet. 1, 507–537 (2000).

    CAS  Article  PubMed  Google Scholar 

  2. Liu, C. C., Liu, C. C., Kanekiyo, T., Xu, H. & Bu, G. Nat. Rev. Neurol. 9, 106–118 (2013).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Zhao, H. et al. Nat. Aging https://doi.org/10.1038/s43587-022-00186-z (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Childs, B. G., Durik, M., Baker, D. J. & van Deursen, J. M. Nat. Med. 21, 1424–1435 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Uccelli, A., Moretta, L. & Pistoia, V. Nat. Rev. Immunol. 8, 726–736 (2008).

    CAS  Article  PubMed  Google Scholar 

  6. Freund, A., Laberge, R. M., Demaria, M. & Campisi, J. Mol. Biol. Cell 23, 2066–2075 (2012).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Shimi, T. et al. Genes Dev. 25, 2579–2593 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Dou, Z. et al. Nature 527, 105–109 (2015).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Xu, C. et al. Nat. Cell Biol. 22, 1170–1179 (2020).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Narita, M. et al. Cell 113, 703–716 (2003).

    CAS  Article  PubMed  Google Scholar 

  11. Gorbunova, V. et al. Nature 596, 43–53 (2021).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Iyengar, S. & Farnham, P. J. J. Biol. Chem. 286, 26267–26276 (2011).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Li, X., Egervari, G., Wang, Y., Berger, S. L. & Lu, Z. Nat. Rev. Mol. Cell Biol. 19, 563–578 (2018).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Bussian, T. J. et al. Nature 562, 578–582 (2018).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Zhang, P. et al. Nat. Neurosci. 22, 719–728 (2019).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

L.W. is supported by National Institute on Aging grant K99AG065500. Z.D. is supported by National Institute of Health grants R35GM137889, R00AG053406, UG3CA268117, Glenn Foundation for Medical Research and AFAR, and Longevity Impetus Grant.

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Authors and Affiliations

  1. Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Lu Wang

  2. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA

    Zhixun Dou

  3. Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA

    Zhixun Dou

  4. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Zhixun Dou

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  1. Lu Wang
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  2. Zhixun Dou
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Correspondence to Lu Wang or Zhixun Dou.

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Wang, L., Dou, Z. Apolipoprotein E regulates chromatin stability and senescence. Nat Aging 2, 282–284 (2022). https://doi.org/10.1038/s43587-022-00190-3

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