Male rat leukocyte population dynamics predict a window for intervention in aging

Abstract

Many age-associated changes in the human hematopoietic system have been reproduced in murine models; however, such changes have not been as robustly explored in rats despite the fact these larger rodents are more physiologically similar to humans. We examined peripheral blood of male F344 rats ranging from three to twenty-seven months of age and found significant age-associated changes with distinct leukocyte population shifts. We report CD25+ CD4+ population frequency is a strong predictor of healthy aging, generate a model using blood parameters, and find rats with blood profiles that diverge from chronologic age indicate debility; thus, assessments of blood composition may be useful for non-lethal disease profiling or as a surrogate measure for efficacy of aging interventions. Importantly, blood parameters and DNA methylation alterations, defined distinct juncture points during aging, supporting a non-linear aging process. Our results suggest these inflection points are important considerations for aging interventions. Overall, we present rat blood aging metrics that can serve as a resource to evaluate health and the effects of interventions in a model system physiologically more reflective of humans.

Data availability

The data that support the findings of this study are available in the Supplementary Material and Supplementary Tables of this article. The DNA methylation raw data is available via GEO Accession (GSE161141). FCS files have been uploaded to FlowRepository (FR-FCM-Z59K)

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Hagai Yanai

    Flow Cytometry Core, National Institute on Aging, Baltimore, United States
    For correspondence
    hagai.yanai@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
  2. Christopher Dunn

    Flow Cytometry Core, National Institute on Aging, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7899-0110
  3. Bongsoo Park

    Epigenetics and Stem Cell Unit, National Institute on Aging, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Christopher Coletta

    Computational Biology and Genomics Core, National Institute on Aging, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ross A McDevitt

    Comparative Medicine Section, National Institute on Aging, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3722-9047
  6. Taylor McNeely

    Epigenetics and Stem Cell Unit, National Institute on Aging, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael Leone

    Epigenetics and Stem Cell Unit, National Institute on Aging, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Robert P Wersto

    Flow Cytometry Core, National Institute on Aging, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Kathy A Perdue

    Comparative Medicine Section, National Institute on Aging, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Isabel Beerman

    Epigenetics and Stem Cell Unit, National Institute on Aging, Baltimore, United States
    For correspondence
    isabel.beerman@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7758-8231

Funding

National Institutes of Health (Intramural NIA)

  • Isabel Beerman

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

Ethics

Animal experimentation: All experimental procedures were conducted in accordance with the Guide for the Care and Use of Laboratory Animals and approved by the NIA Animal Care and Use Committee (ASP 467-CMS-2018 and 469-TGB-2022)

Reviewing Editor

  1. Bérénice A Benayoun, University of Southern California, United States

Publication history

  1. Received: January 5, 2022
  2. Accepted: May 3, 2022
  3. Accepted Manuscript published: May 4, 2022 (version 1)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Hagai Yanai
  2. Christopher Dunn
  3. Bongsoo Park
  4. Christopher Coletta
  5. Ross A McDevitt
  6. Taylor McNeely
  7. Michael Leone
  8. Robert P Wersto
  9. Kathy A Perdue
  10. Isabel Beerman
(2022)
Male rat leukocyte population dynamics predict a window for intervention in aging
eLife 11:e76808.
https://doi.org/10.7554/eLife.76808

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