Skip to main content
SpringerLink
Log in

Senescent cells, senolytics and tissue repair: the devil may be in the dosing

  • Comment
  • Published:

From Nature Aging

View current issue Submit your manuscript

There is tremendous interest in the development of drugs that target senescent cells (‘senolytic’ drugs) to treat a range of age-related morbidities. However, studies in mice that demonstrate impaired tissue repair following clearance of senescent cells raise questions about the potential risks of senolytic therapies. Closer examination of the available studies reveals the hopeful possibility of a ‘therapeutic window’ in which these risks can be minimized.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1: Schematic of postulated effects of continuous versus intermittent senolytic treatment on tissue repair.

References

  1. Khosla, S., Farr, J. N., Tchkonia, T. & Kirkland, J. L. Nat. Rev. Endocrinol. 16, 263–275 (2020).

    Article  CAS  PubMed  Google Scholar 

  2. Raffaele, M. & Vinciguerra, M. Lancet Healthy Longev. 3, e67–e77 (2022).

    Article  PubMed  Google Scholar 

  3. Hickson, L. J. et al. EBioMed. 47, 446–456 (2019).

    Article  Google Scholar 

  4. Justice, J. N. et al. EBioMed. 40, 554–563 (2019).

    Article  Google Scholar 

  5. Kowald, A., Passos, J. F. & Kirkwood, T. B. L. Aging Cell 19, e13270 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Demaria, M. et al. Dev. Cell 31, 722–733 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Reyes, N. S. et al. Science 378, 192–201 (2022).

    Article  CAS  PubMed  Google Scholar 

  8. Grosse, L. et al. Cell Metab. 32, 87–99 (2020).

    Article  CAS  PubMed  Google Scholar 

  9. Yun, M. H., Davaapil, H. & Brockes, J. P. eLife 4, e05505 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hewitt, G. et al. Nat. Commun. 3, 708 (2012).

    Article  PubMed  Google Scholar 

  11. Saul, D. et al. eLife 10, e69958 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Liu, J. et al. J. Clin. Invest. 132, e148073 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Schafer, M. J. et al. Nat. Commun. 8, 14532 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ritschka, B. et al. Genes Dev. 31, 172–183 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Farr, J. N. et al. Nat. Med. 23, 1072–1079 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

S.K. is supported by grants P01 AG062413, R01 AG076515 and U54 AG079754.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Mayo Clinic, Rochester, MN, USA

    Sundeep Khosla

  2. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA

    Sundeep Khosla

Authors
  1. Sundeep Khosla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sundeep Khosla.

Ethics declarations

Competing interests

The author declares has no competing interests.

Peer review

Peer review information

Nature Aging thanks Eiji Hara and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khosla, S. Senescent cells, senolytics and tissue repair: the devil may be in the dosing. Nat Aging 3, 139–141 (2023). https://doi.org/10.1038/s43587-023-00365-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s43587-023-00365-6

  • Springer Nature America, Inc.

Search

Navigation