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Poor mitochondrial health and systemic inflammation? Test of a classic hypothesis in the Baltimore Longitudinal Study of Aging

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Abstract

Although a persistent inflammatory state has long been associated with aging and negative health outcomes, the underlying mechanisms remain unclear. Mitochondrial dysfunction has been proposed as a cause of inflammaging, but evidence of an association in humans is lacking. In this study, we analyzed the cross-sectional association between inflammatory biomarkers and mitochondrial oxidative capacity in skeletal muscle, assessed as post-exercise phosphocreatine recovery time constant by phosphorus magnetic resonance spectroscopy, in a population of 669 adults (mean age 67 years) from the Baltimore Longitudinal Study of Aging. We observed that participants with lower mitochondrial oxidative capacity exhibited hallmarks of inflammation, specifically markedly higher levels of interleukin-6 and C-reactive protein, as well as increased erythrocyte sedimentation rate when compared with participants with better oxidative capacity, independent of age and sex. We speculate that this association reflects the observation that products of damaged mitochondria, such as mitochondrial DNA, activate multiple pathways that lead to inflammation. Furthermore, excess production of oxidative species (ROS) by dysfunctional mitochondria could trigger inflammation either directly via NF-κB or through oxidative damage to proteins, lipids, and nucleic acids. Longitudinal studies are necessary to ascertain whether and through which mechanisms mitochondrial dysfunction activate inflammation or whether both these phenomena derive from a common root.

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Funding

This work was supported by the Intramural Research Program of the National Institute on Aging.

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Authors and Affiliations

  1. National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Suite 100, Baltimore, MD, 21224, USA

    Marta Zampino, Pei-Lun Kuo, Richard G. Spencer, Kenneth W. Fishbein, Eleanor M. Simonsick & Luigi Ferrucci

  2. SUNY Upstate Medical University, Syracuse, NY, USA

    Nicholas A. Brennan

Authors
  1. Marta Zampino
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  2. Nicholas A. Brennan
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  3. Pei-Lun Kuo
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  4. Richard G. Spencer
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  5. Kenneth W. Fishbein
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  6. Eleanor M. Simonsick
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  7. Luigi Ferrucci
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Correspondence to Luigi Ferrucci.

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The study protocol was approved by the Institutional Review Board of the National Institute of Environmental Health Sciences (NIEHS, NC). All participants consented to participate in the study, after receiving detailed descriptions at every visit.

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The authors declare that they have no conflict of interest.

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Zampino, M., Brennan, N.A., Kuo, PL. et al. Poor mitochondrial health and systemic inflammation? Test of a classic hypothesis in the Baltimore Longitudinal Study of Aging. GeroScience 42, 1175–1182 (2020). https://doi.org/10.1007/s11357-020-00208-x

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  • DOI: https://doi.org/10.1007/s11357-020-00208-x

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