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Targeting Senescent Cells in Fibrosis: Pathology, Paradox, and Practical Considerations

  • Scleroderma (J Varga, Section Editor)
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Abstract

Purpose of the Review

Senescent cells have the capacity to both effect and limit fibrosis. Senotherapeutics target senescent cells to improve aging conditions. Here, we review the contexts in which senescent cells mediate wound healing and fibrotic pathology and the potential utility of senotherapeutic drugs for treatment of fibrotic disease.

Recent Findings

Multi-action and temporal considerations influence deleterious versus beneficial actions of senescent cells. Acutely generated senescent cells can limit proliferation, and the senescence-associated secretory phenotype (SASP) contains factors that can facilitate tissue repair. Long-lived senescent cells that evade clearance or are generated outside of programmed remodeling can deplete the progenitor pool to exhaust regenerative capacity and through the SASP, stimulate continual activation, leading to disorganized tissue architecture, fibrotic damage, sterile inflammation, and induction of bystander senescence.

Summary

Senescent cells contribute to fibrotic pathogenesis in multiple tissues, including the liver, kidney, and lung. Senotherapeutics may be a viable strategy for treatment of a range of fibrotic conditions.

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Acknowledgments

The authors would also like to thank Matthew M. Moore from the Mayo Clinic Center for Innovation for help with the illustration.

Funding

We gratefully acknowledge support from the Glenn/AFAR post-doctoral fellowship program for translational research on aging (M.J.S.), the National Institutes of Health HL092961 (D.J.T.) and AG052958 (N.K.L.), and the John E. and Virginia H. Kunkel Family (N.K.L).

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Authors and Affiliations

  1. Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA

    Marissa J. Schafer & Nathan K. LeBrasseur

  2. Department of Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA

    Marissa J. Schafer & Nathan K. LeBrasseur

  3. Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA

    Andrew J. Haak, Daniel J. Tschumperlin & Nathan K. LeBrasseur

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  1. Marissa J. Schafer
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  2. Andrew J. Haak
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  3. Daniel J. Tschumperlin
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  4. Nathan K. LeBrasseur
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Correspondence to Nathan K. LeBrasseur.

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Conflict of Interest

Dr. LeBrasseur has patent killing senescent cells and treating senescence-associated conditions issued and patent compositions and methods for treating senescence-associated diseases and disorders issued. Drs. Schafer, Haak, and Tschumperlin have no conflicts of interest to disclose.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Scleroderma

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Schafer, M.J., Haak, A.J., Tschumperlin, D.J. et al. Targeting Senescent Cells in Fibrosis: Pathology, Paradox, and Practical Considerations. Curr Rheumatol Rep 20, 3 (2018). https://doi.org/10.1007/s11926-018-0712-x

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