Oxidative stress and the mitochondrial theory of aging in human skeletal muscle.
According to the mitochondrial theory of aging, an age-related increase in oxidative stress is responsible for cellular damage and ultimately cell death. Despite compelling evidence that supports the mitochondrial theory of aging in some tissues, data regarding aging skeletal muscle are inconsistent. We collected resting muscle biopsies from the vastus lateralis, and 24 h urine samples from, young (N = 12, approximately 22 yr), and older (N = 12 approximately 72 yr) men. Urinary 8-OHdG was significantly higher in older as compared to younger men (Old: 7714 +/- 1402, Young: 5333 +/- 1191 ng g(-1) creatinine: p = 0.005), as were levels of protein carbonyls (Old: 0.72 +/- 0.42, Young: 0.26 +/- 0.14 nmol mg(-1) protein: p = 0.007). MnSOD activity (Old: 7.1 +/- 0.8, Young: 5.2 +/- 1.8 U mg(-1) protein: p = 0.04) and catalase activity (Old: 8.5 +/- 2.0, Young: 6.2 +/- 2.4 micro mol min(-1) mg(-1) protein: p = 0.03) were significantly higher in old as compared to young men, respectively, with no differences observed for total or CuZnSOD. Full-length mtDNA appeared lower in old as compared to young men, and mtDNA deletions were present in 6/8 old and 0/6 young men (p = 0.003). The maximal activities of citrate synthase, and complex II+III, and IV were not different between young and old men, however, complex I+III activity was marginally higher in older as compared to younger men (Old: 2.5 +/- 0.5, Young: 1.9 +/- 0.5 micromol min(-1) g(-1) w.w: p = 0.03) respectively. In conclusion, healthy aging is associated with oxidative damage to proteins and DNA, a compensatory up-regulation of antioxidant enzymes, and aberrations of mtDNA, with no reduction in electron transport chain maximal enzyme activity.
Department of Kinesiology, McMaster University, Hamilton, Ont., Canada.
Parise
P
Gianni
Kaczor J
KJ
Jan
Mahoney J
MJ
Douglas
Phillips M
PM
Stuart
Mark A
MA
Tarnopolsky
D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology*; D000886:Anthropometry; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics*; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000235:genetics* / Q000502:physiology
D000975:Antioxidants; D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins