TY - JOUR

T1 - A novel method for determining human ex vivo submaximal skeletal muscle mitochondrial function

AU - Hey-Mogensen, Martin

AU - Gram, Martin

AU - Jensen, Martin Borch

AU - Lund, Michael Taulo

AU - Hansen, Christina Neigaard

AU - Scheibye-Knudsen, Morten

AU - Bohr, Vilhelm A.

AU - Dela, Flemming

N1 - This article is protected by copyright. All rights reserved.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - In spite of numerous studies there is no consensus whether mitochondrial function is altered with increased age. The novelty of the present study is the determination of mitochondrial function at submaximal activity rates which is more physiological relevant than the ex vivo functionality protocols previously used. Muscle biopsies were taken from 64 old or young male subjects (60-70 or 20-30 years old). Aged subjects were recruited as trained or untrained. Muscle biopsies were used for isolation of mitochondria and subsequent measurements of DNA repair, antioxidant capacity and mitochondrial protein levels (complex I-V). Mitochondrial function was determined by simultaneous measures of oxygen consumption, membrane potential and hydrogen peroxide emission using pyruvate+malate (PM) or succinate+rotenone (SR) as substrates. Proton leak was lower in aged subjects when determined at the same membrane potential and was not affected by training status. State 3 respiration was lower in the aged untrained subjects. This effect, however, was alleviated in the aged trained subjects. H2 O2 emission with PM was higher in the aged subjects, and exacerbated by training, but was not changed when using SR. However, with higher manganese superoxide dismuthase (MnSOD) content the trained aged subjects may actually have lower or similar mitochondrial superoxide emission when compared with the untrained subjects. We conclude that aging, and the physical activity level in aged subjects, are both related to changes in the intrinsic functionality of the mitochondrion in skeletal muscle. Both these changes could be important factors in determining the metabolic health of the aged skeletal muscle cell. This article is protected by copyright. All rights reserved.

AB - In spite of numerous studies there is no consensus whether mitochondrial function is altered with increased age. The novelty of the present study is the determination of mitochondrial function at submaximal activity rates which is more physiological relevant than the ex vivo functionality protocols previously used. Muscle biopsies were taken from 64 old or young male subjects (60-70 or 20-30 years old). Aged subjects were recruited as trained or untrained. Muscle biopsies were used for isolation of mitochondria and subsequent measurements of DNA repair, antioxidant capacity and mitochondrial protein levels (complex I-V). Mitochondrial function was determined by simultaneous measures of oxygen consumption, membrane potential and hydrogen peroxide emission using pyruvate+malate (PM) or succinate+rotenone (SR) as substrates. Proton leak was lower in aged subjects when determined at the same membrane potential and was not affected by training status. State 3 respiration was lower in the aged untrained subjects. This effect, however, was alleviated in the aged trained subjects. H2 O2 emission with PM was higher in the aged subjects, and exacerbated by training, but was not changed when using SR. However, with higher manganese superoxide dismuthase (MnSOD) content the trained aged subjects may actually have lower or similar mitochondrial superoxide emission when compared with the untrained subjects. We conclude that aging, and the physical activity level in aged subjects, are both related to changes in the intrinsic functionality of the mitochondrion in skeletal muscle. Both these changes could be important factors in determining the metabolic health of the aged skeletal muscle cell. This article is protected by copyright. All rights reserved.

U2 - 10.1113/JP270204

DO - 10.1113/JP270204

M3 - Journal article

C2 - 26096709

VL - 593

SP - 3991

EP - 4010

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - 17

ER -