Weakness of whole muscles in mice deficient in Cu, Zn superoxide dismutase is not explained by defects at the level of the contractile apparatus.
Mice deficient in Cu,Zn superoxide dismutase (Sod1 (-/-) mice) demonstrate elevated oxidative stress associated with rapid age-related declines in muscle mass and force. The decline in mass for muscles of Sod1 (-/-) mice is explained by a loss of muscle fibers, but the mechanism underlying the weakness is not clear. We hypothesized that the reduced maximum isometric force (F o) normalized by cross-sectional area (specific F o) for whole muscles of Sod1 (-/-) compared with wild-type (WT) mice is due to decreased specific F o of individual fibers. Force generation was measured for permeabilized fibers from muscles of Sod1 (-/-) and WT mice at 8 and 20 months of age. WT mice were also studied at 28 months to determine whether any deficits observed for fibers from Sod1 (-/-) mice were similar to those observed in old WT mice. No effects of genotype were observed for F o or specific F o at either 8 or 20 months, and no age-associated decrease in specific F o was observed for fibers from Sod1 (-/-) mice, whereas specific F o for fibers of WT mice decreased by 20 % by 28 months. Oxidative stress has also been associated with decreased maximum velocity of shortening (V max), and we found a 10 % lower V max for fibers from Sod1 (-/-) compared with WT mice at 20 months. We conclude that the low specific F o of muscles of Sod1 (-/-) mice is not explained by damage to contractile proteins. Moreover, the properties of fibers of Sod1 (-/-) mice do not recapitulate those observed with aging in WT animals.
Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Lisa M
LM
Larkin
Michael C
MC
Hanes
Erdan
E
Kayupov
Dennis R
DR
Claflin
John A
JA
Faulkner
Susan V
SV
Brooks
D000375:Aging / Q000502:physiology*; D000818:Animals; D003300:Copper / Q000172:deficiency; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology*; D018908:Muscle Weakness / Q000378:metabolism / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D015032:Zinc / Q000172:deficiency
D003300:Copper; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D015032:Zinc