1. Computational and Systems Biology
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A cross-sectional study of functional and metabolic changes during aging through the lifespan in male mice.

  1. Michael A Petr
  2. Irene Alfaras
  3. Melissa Krawcyzk
  4. Woei-Nan Bair
  5. Sarah J Mitchell
  6. Christopher H Morrell
  7. Stephanie A Studenski
  8. Nathan L Price
  9. Kenneth W Fishbein
  10. Richard G Spencer
  11. Morten Scheibye-Knudsen
  12. Edward G Lakatta
  13. Luigi Ferrucci
  14. Miguel A Aon
  15. Michel Bernier
  16. Rafael de Cabo  Is a corresponding author
  1. University of Copenhagen, Denmark
  2. University of Pittsburgh, United States
  3. National Institute on Aging, NIH, United States
  4. University of Sciences, United States
  5. ETH Zürich, Switzerland
  6. Yale University, United States
Research Article
  • Cited 3
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Cite this article as: eLife 2021;10:e62952 doi: 10.7554/eLife.62952

Abstract

Aging is associated with distinct phenotypical, physiological, and functional changes, leading to disease and death. The progression of aging-related traits varies widely among individuals, influenced by their environment, lifestyle, and genetics. In this study, we conducted physiologic and functional tests cross-sectionally throughout the entire lifespan of male C57BL/6N mice. In parallel, metabolomics analyses in serum, brain, liver, heart, and skeletal muscle were also performed to identify signatures associated with frailty and age-dependent functional decline. Our findings indicate that declines in gait speed as a function of age and frailty are associated with a dramatic increase in the energetic cost of physical activity and decreases in working capacity. Aging and functional decline prompt organs to rewire their metabolism and substrate selection and towards redox-related pathways, mainly in liver and heart. Collectively, the data provide a framework to further understand and characterize processes of aging at the individual organism and organ levels.

Data availability

This study did not generate datasets or code. However, we are citing one of our previously published raw microarray datasets that was deposited to the NCBI GeneExpressionOmnibus database under accession number GSE81959.

The following previously published data sets were used

Article and author information

Author details

  1. Michael A Petr

    Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  2. Irene Alfaras

    Aging Institute, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Melissa Krawcyzk

    Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Woei-Nan Bair

    Department of Physical Therapy, University of Sciences, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sarah J Mitchell

    Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Christopher H Morrell

    Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Stephanie A Studenski

    Department of Medicine, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Nathan L Price

    Department of Comparative Medicine, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Kenneth W Fishbein

    Laboratory of Clinical Investigator, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Richard G Spencer

    Laboratory Clinical Investigation, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Morten Scheibye-Knudsen

    Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  12. Edward G Lakatta

    Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Luigi Ferrucci

    Intramural Research Program, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6273-1613
  14. Miguel A Aon

    Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Michel Bernier

    Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Rafael de Cabo

    Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, United States
    For correspondence
    decabora@grc.nia.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2830-5693

Funding

National Institute on Aging (AG000335-04)

  • Rafael de Cabo

The research was supported by the Intramural Research Program of the National Institute on Aging

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 (ACUC) protocol of the National Institute on Aging (Protocol Number: TGB-277-2022)

Reviewing Editor

  1. Jamie Justice, Wake Forest School of Medicine, United States

Publication history

  1. Received: September 10, 2020
  2. Accepted: April 13, 2021
  3. Accepted Manuscript published: April 20, 2021 (version 1)
  4. Version of Record published: May 5, 2021 (version 2)

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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