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

79 Citations (Scopus)

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 H 2 O 2 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 H 2 O 2 emission is not increased with aging, mitochondrial ADP sensitivity is impaired. This resulted in an increase in mitochondrial H 2 O 2 and the fraction of electron leak to H 2 O 2 , 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 H 2 O 2 emission rates in the presence of ADP, the fraction of electron leak to H 2 O 2 , or the redox state of the muscle. These data establish that a reduction in mitochondrial ADP sensitivity increases mitochondrial H 2 O 2 emission and contributes to age-associated redox stress. Holloway et al. show that an inability of ADP to decrease mitochondrial reactive oxygen species emission contributes to redox stress in skeletal muscle tissue of older individuals and that this process is not recovered following prolonged resistance-type exercise training, despite the general benefits of resistance training for muscle health.

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

Keywords

  • ADP
  • aging
  • bioenergetics
  • exercise
  • H O
  • mitochondria
  • muscle
  • resistance training
  • respiration
  • ROS

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