Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging.
Mitochondrial function, hydrogen peroxide generation and oxidative damage were measured in hind-limb skeletal muscle from young (6-8 month) and old (27-29 month) wildtype and heterozygous Mn-superoxide dismutase (MnSOD) knockout mice (Sod2(+/-)). The reduction in MnSOD activity in the Sod2(+/-) mice makes these mice a good model to examine the implications of life-long elevated endogenous mitochondrial oxidative stress on mitochondrial function. ATP production was reduced approximately 30% with age in skeletal muscle mitochondria isolated from wildtype mice, and reduced 40-45% in mitochondria from both young and old Sod2(+/-) mice compared to the young wildtype mice. Release of hydrogen peroxide from skeletal muscle mitochondria increased 40-50% with age in both wildtype and Sod2(+/-) but was not higher in mitochondria from Sod2(+/-) mice. Activities of electron transport Complexes I and V were decreased 25-30% in both young and old Sod2(+/-) mice compared to wildtype mice, and were 25-30% lower in mitochondria from old wildtype and old Sod2(+/-) mice. DNA oxidative damage (oxo8dG levels) increased more than 45% with age and over 130% in the young Sod2(+/-) mice compared to the wildtype mice. These data show that mitochondrial oxidative stress in mouse skeletal muscle is increased with age, leading to alterations in mitochondrial function. In addition, increased oxidative stress generated by reduced activity of MnSOD does not exacerbate these alterations during aging.
Mansouri
Abdellah
A
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3901, USA.
Muller
Florian L
FL
Liu
Yuhong
Y
Ng
Rainer
R
Faulkner
John
J
Hamilton
Michelle
M
Richardson
Arlan
A
Huang
Ting-Ting
TT
Epstein
Charles J
CJ
Van Remmen
Holly
H
D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004249:DNA Damage; D004579:Electron Transport; D005260:Female; D006614:Hindlimb / Q000201:enzymology / Q000473:pathology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000172:deficiency / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2