Weakness of whole muscles in mice deficient in Cu, Zn superoxide dismutase is not explained by defects at the level of the contractile apparatus

作者：Larkin Lisa M; Hanes Michael C; Kayupov Erdan; Claflin Dennis R; Faulkner John A; Brooks Susan V^*

来源：Age, 2013, 35(4): 1173-1181.

DOI：10.1007/s11357-012-9441-7

• Contractility
• Oxidative stress
• Permeabilized fiber
• Skeletal muscle
• Specific force

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.

• 出版日期2013-8