Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle

Graham P. Holloway*, Andrew M. Holwerda, Paula M. Miotto, Marlou L. Dirks, Lex B. Verdijk, Luc J. C. van Loon

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Web of Science)

Abstract

It remains unknown if mitochondrial bioenergetics are altered with aging in humans. We established an in vitro method to simultaneously determine mitochondrial respiration and H2O2 emission in skeletal muscle tissue across a range of biologically relevant ADP concentrations. Using this approach, we provide evidence that, although the capacity for mitochondrial H2O2 emission is not increased with aging, mitochondrial ADP sensitivity is impaired. This resulted in an increase in mitochondrial H2O2 and the fraction of electron leak to H2O2, in the presence of virtually all ADP concentrations examined. Moreover, although prolonged resistance training in older individuals increased muscle mass, strength, and maximal mitochondrial respiration, exercise training did not alter H2O2 emission rates in the presence of ADP, the fraction of electron leak to H2O2, or the redox state of the muscle. These data establish that a reduction in mitochondrial ADP sensitivity increases mitochondrial H2O2 emission and contributes to age-associated redox stress.

Original languageEnglish
Pages (from-to)2837-2848
Number of pages12
JournalCell Reports
Volume22
Issue number11
DOIs
Publication statusPublished - 13 Mar 2018

Keywords

  • ADENINE-NUCLEOTIDE TRANSLOCASE
  • OXIDATIVE STRESS
  • IN-VIVO
  • INSULIN-RESISTANCE
  • ELDERLY-MEN
  • PERMEABILITY TRANSITION
  • PROTEIN SUPPLEMENTATION
  • SUPEROXIDE-PRODUCTION
  • RESPIRATORY CONTROL
  • H2O2 EMISSION

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