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Age-Dependent Changes in the Production of Mitochondrial Reactive Oxygen Species in Human Skeletal Muscle

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Abstract

A decrease in muscle mass and its functionality (strength, endurance, and insulin sensitivity) is one of the integral signs of aging. One of the triggers of aging is an increase in the production of mitochondrial reactive oxygen species. Our study was the first to examine age-dependent changes in the production of mitochondrial reactive oxygen species related to a decrease in the proportion of mitochondria-associated hexokinase-2 in human skeletal muscle. For this purpose, a biopsy was taken from m. vastus lateralis in 10 young healthy volunteers and 70 patients (26-85 years old) with long-term primary arthrosis of the knee/hip joint. It turned out that aging (comparing different groups of patients), in contrast to inactivity/chronic inflammation (comparing young healthy people and young patients), causes a pronounced increase in peroxide production by isolated mitochondria. This correlated with the age-dependent distribution of hexokinase-2 between mitochondrial and cytosolic fractions, a decrease in the rate of coupled respiration of isolated mitochondria and respiration when stimulated with glucose (a hexokinase substrate). It is discussed that these changes may be caused by an age-dependent decrease in the content of cardiolipin, a potential regulator of the mitochondrial microcompartment containing hexokinase. The results obtained contribute to a deeper understanding of age-related pathogenetic processes in skeletal muscles and open prospects for the search for pharmacological/physiological approaches to the correction of these pathologies.

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Abbreviations

mROS:

mitochondrial reactive oxygen species

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Funding

The work was supported by the Russian Science Foundation (grant no. 21-15-00405, study with healthy volunteers, experiments with mitochondrial respiration) and by the State Assignment of Lomonosov Moscow State University (study with patients, clinical and histological studies).

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Authors and Affiliations

  1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Moscow, Russia

    Mikhail Yu. Vyssokikh & Vladimir P. Skulachev

  2. National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V. I. Kulakov, 117997, Moscow, Russia

    Mikhail Yu. Vyssokikh, Mariya V. Marey & Ludmila A. Manukhova

  3. Institute of Biomedical Problems, Russian Academy of Sciences, 123007, Moscow, Russia

    Mikhail Yu. Vyssokikh, Tatiana F. Vepkhvadze, Nadezhda S. Kurochkina & Daniil V. Popov

  4. Medical Research and Education Center, Lomonosov Moscow State University, 119192, Moscow, Russia

    Maksim A. Vigovskiy, Vladislav V. Philippov, Yakov R. Boroday, Olga A. Grigorieva & Anastasiya Yu. Efimenko

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  1. Mikhail Yu. Vyssokikh
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Contributions

M.Yu.V., A.Yu.E., D.V.P., and V.P.S. concept and management of the work; M.Yu.V., M.A.V., V.V.Ph., Ya.R.B., M.V.M., O.A.G., T.F.V., N.S.K., and L.A.M. conducting experiments; M.Yu.V., M.A.V., A.Yu.E., D.V.P., and V.P.S. discussion of the research results; M.Yu.V., A.Yu.E., and D.V.P. text writing; M.Yu.V., A.Yu.E., and D.V.P. editing the text of the article.

Corresponding author

Correspondence to Mikhail Yu. Vyssokikh.

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All studies were conducted in accordance with the principles of biomedical ethics as outlined in the 1964 Declaration of Helsinki and its later amendments. Each participant in the study provided a voluntary written informed consent after receiving an explanation of the potential risks and benefits, as well as the nature of the upcoming study. The authors of this work declare that they have no conflicts of interest.

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Vyssokikh, M.Y., Vigovskiy, M.A., Philippov, V.V. et al. Age-Dependent Changes in the Production of Mitochondrial Reactive Oxygen Species in Human Skeletal Muscle. Biochemistry Moscow 89, 299–312 (2024). https://doi.org/10.1134/S0006297924020093

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