Reduced oxidative power but unchanged antioxidative capacity in skeletal muscle from aged humans.
The hypothesis that the aging process is associated with mitochondrial dysfunction and oxidative stress has been investigated in human skeletal muscle. Muscle biopsy samples were taken from seven old male subjects [OS; 75 (range 61-86) years] and eight young male subjects [YS; 25 (22-31) years]. Oxidative function was measured both in permeabilised muscle fibres and isolated mitochondria. Despite matching the degree of physical activity, OS had a lower training status than YS as judged from pulmonary maximal O(2) consumption ( Vdot;O(2)max, -36%) and handgrip strength (-20%). Both maximal respiration and creatine-stimulated respiration were reduced in muscle fibres from OS (-32 and -34%, respectively). In contrast, respiration in isolated mitochondria was similar in OS and YS. The discrepancy might be explained by a biased harvest of "healthy" mitochondria and/or disruption of structural components during the process of isolation. Cytochrome C oxidase was reduced (-40%, P<0.01), whereas UCP3 protein tended to be elevated in OS ( P=0.09). Generation of reactive oxygen species by isolated mitochondria and measures of antioxidative defence (muscle content of glutathione, glutathione redox status, antioxidative enzymes activity) were not significantly different between OS and YS. It is concluded that aging is associated with mitochondrial dysfunction, which appears to be unrelated to reduced physical activity. The hypothesis of increased oxidative stress in aged muscle could not be confirmed in this study.
Tonkonogi
Michail
M
Department of Physiology and Pharmacology, Karolinska Institutet, Box 5626, 114 86, Stockholm, Sweden. Michail.Tonkonogi@fyfa.ki.se
Fernström
Maria
M
Walsh
Brandon
B
Ji
Li Li
LL
Rooyackers
Olav
O
Hammarqvist
Folke
F
Wernerman
Jan
J
Sahlin
Kent
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D019069:Cell Respiration / Q000502:physiology; D018737:Hand Strength / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D018709:Statistics, Nonparametric
D000975:Antioxidants; D011451:Prostaglandin-Endoperoxide Synthases