Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle
Journal article
Holloway, Graham P., Holwerda, Andrew M., Miotto, Paula M., Dirks, Marlou L., Verdijk, Lex B. and Van Loon, Luc. (2018). Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle. Cell Reports. 22(11), pp. 2837 - 2848. https://doi.org/10.1016/j.celrep.2018.02.069
Authors | Holloway, Graham P., Holwerda, Andrew M., Miotto, Paula M., Dirks, Marlou L., Verdijk, Lex B. and Van Loon, Luc |
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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 H2O2emission in skeletal muscle tissue across a range of biologically relevant ADP concentrations. Using this approach, we provide evidence that, although the capacity for mitochondrial H2O2emission is not increased with aging, mitochondrial ADP sensitivity is impaired. This resulted in an increase in mitochondrial H2O2and the fraction of electron leak to H2O2, in the presence of virtually all ADP concentrations examined. Moreover, although prolonged resistance training inolder individuals increased muscle mass, strength, and maximal mitochondrial respiration, exercise training did not alter H2O2emission 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 H2O2emission 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 redoxstress 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. |
Keywords | ADP; aging; bioenergetics; exercise; H2O2; mitochondria; muscle; resistance training; respiration; ROS |
Year | 2018 |
Journal | Cell Reports |
Journal citation | 22 (11), pp. 2837 - 2848 |
Publisher | Elsevier Inc. |
ISSN | 2211-1247 |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.celrep.2018.02.069 |
Scopus EID | 2-s2.0-85043587704 |
Open access | Open access |
Page range | 2837 - 2848 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | |
Place of publication | United States |
https://acuresearchbank.acu.edu.au/item/8v7v3/age-associated-impairments-in-mitochondrial-adp-sensitivity-contribute-to-redox-stress-in-senescent-human-skeletal-muscle
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