Mitochondrial functional impairment with aging is exaggerated in isolated mitochondria compared to permeabilized myofibers
Martin Picard
Department of Kinesiology, McGill University, Montreal, QC H2W 1S4, Canada
These authors contributed equally to this work.
Search for more papers by this authorDarmyn Ritchie
Muscle & Aging Laboratory, Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
These authors contributed equally to this work.
Search for more papers by this authorKathryn J. Wright
Muscle & Aging Laboratory, Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Search for more papers by this authorCaroline Romestaing
Laboratoire de Physiologie Intégrative, Cellulaire et Moléculaire, Université de Lyon, Lyon, France
Search for more papers by this authorMelissa M. Thomas
Muscle & Aging Laboratory, Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Search for more papers by this authorSharon L. Rowan
Muscle & Aging Laboratory, Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Search for more papers by this authorTanja Taivassalo
Department of Kinesiology, McGill University, Montreal, QC H2W 1S4, Canada
Search for more papers by this authorRussell T. Hepple
Muscle & Aging Laboratory, Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Search for more papers by this authorMartin Picard
Department of Kinesiology, McGill University, Montreal, QC H2W 1S4, Canada
These authors contributed equally to this work.
Search for more papers by this authorDarmyn Ritchie
Muscle & Aging Laboratory, Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
These authors contributed equally to this work.
Search for more papers by this authorKathryn J. Wright
Muscle & Aging Laboratory, Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Search for more papers by this authorCaroline Romestaing
Laboratoire de Physiologie Intégrative, Cellulaire et Moléculaire, Université de Lyon, Lyon, France
Search for more papers by this authorMelissa M. Thomas
Muscle & Aging Laboratory, Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Search for more papers by this authorSharon L. Rowan
Muscle & Aging Laboratory, Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Search for more papers by this authorTanja Taivassalo
Department of Kinesiology, McGill University, Montreal, QC H2W 1S4, Canada
Search for more papers by this authorRussell T. Hepple
Muscle & Aging Laboratory, Faculty of Kinesiology and Faculty of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Search for more papers by this authorSummary
Mitochondria regulate cellular bioenergetics and apoptosis and have been implicated in aging. However, it remains unclear whether age-related loss of muscle mass, known as sarcopenia, is associated with abnormal mitochondrial function. Two technically different approaches have mainly been used to measure mitochondrial function: isolated mitochondria and permeabilized myofiber bundles, but the reliability of these measures in the context of sarcopenia has not been systematically assessed before. A key difference between these approaches is that contrary to isolated mitochondria, permeabilized bundles contain the totality of fiber mitochondria where normal mitochondrial morphology and intracellular interactions are preserved. Using the gastrocnemius muscle from young adult and senescent rats, we show marked effects of aging on three primary indices of mitochondrial function (respiration, H2O2 emission, sensitivity of permeability transition pore to Ca2+) when measured in isolated mitochondria, but to a much lesser degree when measured in permeabilized bundles. Our results clearly demonstrate that mitochondrial isolation procedures typically employed to study aged muscles expose functional impairments not seen in situ. We conclude that aging is associated with more modest changes in mitochondrial function in sarcopenic muscle than suggested previously from isolated organelle studies.
Supporting Information
Fig. S1 Confocal imaging shows lower mitochondrial content in SEN isolated mitochondrial preparations.
Fig. S2 Representative traces of mitochondrial respiration.
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