Abstract

Periodontal disease is an age-associated disorder clinically defined by periodontal bone loss, inflammation of the specialized tissues that surround and support the tooth, and microbiome dysbiosis. Currently, there is no therapy for reversing periodontal disease, and treatment is generally restricted to preventive measures or tooth extraction. The FDA-approved drug rapamycin slows aging and extends lifespan in multiple organisms, including mice. Here we demonstrate that short-term treatment with rapamycin rejuvenates the aged oral cavity of elderly mice, including regeneration of periodontal bone, attenuation of gingival and periodontal bone inflammation, and revertive shift of the oral microbiome toward a more youthful composition. This provides a geroscience strategy to potentially rejuvenate oral health and reverse periodontal disease in the elderly.

Data availability

The V4-16S rDNA sequences in raw format, prior to post-processing and data analysis, have been deposited at the European Nucleotide Archive (ENA) under study accession no. PRJEB35672.Dryad Data link: http://dx.doi.org/10.5061/dryad.f4qrfj6sn

The following data sets were generated

Article and author information

Author details

  1. Jonathan Y An

    Oral Health Sciences and Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8422-8608
  2. Kristopher A Kerns

    University of Washington, Washington, United States
    Competing interests
    No competing interests declared.
  3. Andrew Ouellette

    The Jackson Laboratory, Bar Harbor, United States
    Competing interests
    No competing interests declared.
  4. Laura Robinson

    The Jackson Laboratory, Bar Harbor, United States
    Competing interests
    No competing interests declared.
  5. H Douglas Morris

    The Jackson Laboratory, Bar Harbor, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7942-3748
  6. Catherine Kaczorowski

    The Jackson Laboratory, Bar Harbor, United States
    Competing interests
    No competing interests declared.
  7. So-Il Park

    Oral Health Sciences and Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  8. Title Mekvanich

    Oral Health Sciences and Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  9. Alex Kang

    Oral Health Sciences and Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  10. Jeffrey S McLean

    Department of Periodontics and Oral Health Sciences Adjunct Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9934-5137
  11. Timothy C Cox

    University of Missouri-Kansas City, Kansas City, United States
    Competing interests
    No competing interests declared.
  12. Matt Kaeberlein

    Department of Pathology, University of Washington, Seattle, United States
    For correspondence
    kaeber@uw.edu
    Competing interests
    Matt Kaeberlein, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1311-3421

Funding

National Institute of Dental and Craniofacial Research (DE027254,DE023810,DE020102)

  • Jonathan Y An
  • Jeffrey S McLean

National Institute on Aging (AG054180,AG038070,AG038070)

  • Catherine Kaczorowski

National Institutes of Health (TR002318)

  • Kristopher A Kerns

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Veronica Galvan, UT Health San Antonio, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of Washington (#4359-01) and of the Jackson Laboratory (#06005-A24) .

Version history

  1. Received: December 10, 2019
  2. Accepted: April 17, 2020
  3. Accepted Manuscript published: April 28, 2020 (version 1)
  4. Version of Record published: May 13, 2020 (version 2)

Copyright

© 2020, An et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jonathan Y An
  2. Kristopher A Kerns
  3. Andrew Ouellette
  4. Laura Robinson
  5. H Douglas Morris
  6. Catherine Kaczorowski
  7. So-Il Park
  8. Title Mekvanich
  9. Alex Kang
  10. Jeffrey S McLean
  11. Timothy C Cox
  12. Matt Kaeberlein
(2020)
Rapamycin rejuvenates oral health in aging mice
eLife 9:e54318.
https://doi.org/10.7554/eLife.54318

Share this article

https://doi.org/10.7554/eLife.54318

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