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

Marta Zampino, Nicholas A. Brennan, Pei Lun Kuo, Richard G. Spencer, Kenneth W. Fishbein, Eleanor M. Simonsick, Luigi Ferrucci

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1175-1182
Number of pages8
JournalGeroScience
Volume42
Issue number4
DOIs
StatePublished - Aug 1 2020
Externally publishedYes

Keywords

  • Inflammaging
  • Mitochondria
  • Oxidative stress
  • Phosphorus magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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