Unbiased proteomics, histochemistry, and mitochondrial DNA copy number reveal better mitochondrial health in muscle of high functioning octogenarians

  1. Ceereena Ubaida-Mohien
  2. Sally Spendiff
  3. Alexey Lyashkov
  4. Ruin Moaddel
  5. Norah J MacMillan
  6. Marie-Eve Filion
  7. Jose A Morais
  8. Tanja Taivassalo
  9. Luigi Ferrucci  Is a corresponding author
  10. Russell T Hepple  Is a corresponding author
  1. National Institute on Aging, United States
  2. Children's Hospital of Eastern Ontario, Canada
  3. McGill University, Canada
  4. University of Florida, United States
  5. National Institute on Aging, United States

Abstract

Background: Master athletes prove that preserving a high level of physical function up to very late in life is possible, but the mechanisms responsible for their high function remain unclear.

Methods: We performed muscle biopsies in 15 octogenarian world class track and field masters athletes (MA) and 14 non-athlete age/sex-matched controls (NA) to provide insights into mechanisms for preserving function in advanced age. Muscle samples were assessed for respiratory compromised fibers, mtDNA copy number, and proteomics by liquid-chromatography mass spectrometry.

Results: MA exhibited markedly better performance on clinical function tests and greater cross-sectional area of the vastus lateralis muscle. Proteomics analysis revealed marked differences, where most of the ~800 differentially represented proteins in MA versus NA pertained to mitochondria structure/function such as electron transport capacity (ETC), cristae formation, mitochondrial biogenesis, and mtDNA-encoded proteins. In contrast, proteins from the spliceosome complex and nuclear pore were downregulated in MA. Consistent with proteomics data, MA had fewer respiratory compromised fibers, higher mtDNA copy number, and an increased protein ratio of the cristae-bound ETC subunits relative to the outer mitochondrial membrane protein voltage dependent anion channel. There was a substantial overlap of proteins overrepresented in MA versus NA with proteins that decline with aging and which are higher in physically active than sedentary individuals. However, we also found 176 proteins related to mitochondria that are uniquely differentially expressed in MA.

Conclusions: We conclude that high function in advanced age is associated with preserving mitochondrial structure/function proteins, with under-representation of proteins involved in the spliceosome and nuclear pore complex. Whereas many of these differences in MA appear related to their physical activity habits, others may reflect unique biological (e.g., gene, environment) mechanisms that preserve muscle integrity and function with aging.

Funding: Funding for this study was provided by operating grants from the Canadian Institutes of Health Research (MOP 84408 to TT and MOP 125986 to RTH). Supported in part by the Intramural Research Program of the National Institute on Aging, NIH, Baltimore, MD, United States.

Data availability

The mass spectrometry proteomics data have been deposited to the MassIVE with the dataset identifier MSV000086195 (ftp://MSV000086195@massive.ucsd.edu)

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

Article and author information

Author details

  1. Ceereena Ubaida-Mohien

    Intramural Research Program, 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:" 0000-0002-4301-4758
  2. Sally Spendiff

    Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Alexey Lyashkov

    Intramural Research Program, National Institute on Aging, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ruin Moaddel

    Intramural Research Program, National Institute on Aging, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Norah J MacMillan

    McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Marie-Eve Filion

    McGill University, Monteal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Jose A Morais

    McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Tanja Taivassalo

    Department of Physical Therapy, University of Florida, Gainesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Luigi Ferrucci

    Translational Gerentology Branch, National Institute on Aging, Baltimore, United States
    For correspondence
    ferruccilu@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:" 0000-0002-6273-1613
  10. Russell T Hepple

    Department of Physical Therapy, University of Florida, Gainesville, United States
    For correspondence
    rthepple@ufl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3640-486X

Funding

Canadian Institutes of Health Research (MOP 125986)

  • Russell T Hepple

Canadian Institutes of Health Research (84408)

  • Tanja Taivassalo

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

Reviewing Editor

  1. Maria Grano, University of Bari, Italy

Ethics

Human subjects: Human subjects research was done with prior approval from the Institutional Review Board of the Faculty of Medicine at McGill University (A08-M66-12B) and according to the Declaration of Helsinki. All subjects provided written informed consent.

Version history

  1. Received: September 30, 2021
  2. Preprint posted: November 4, 2021 (view preprint)
  3. Accepted: April 8, 2022
  4. Accepted Manuscript published: April 11, 2022 (version 1)
  5. Version of Record published: May 10, 2022 (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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  1. Ceereena Ubaida-Mohien
  2. Sally Spendiff
  3. Alexey Lyashkov
  4. Ruin Moaddel
  5. Norah J MacMillan
  6. Marie-Eve Filion
  7. Jose A Morais
  8. Tanja Taivassalo
  9. Luigi Ferrucci
  10. Russell T Hepple
(2022)
Unbiased proteomics, histochemistry, and mitochondrial DNA copy number reveal better mitochondrial health in muscle of high functioning octogenarians
eLife 11:e74335.
https://doi.org/10.7554/eLife.74335

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https://doi.org/10.7554/eLife.74335

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