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Acceleration of age‐related skeletal muscle atrophy and oxidative stress in the mice lacking of CuZnSOD
Author(s) -
Song Wook,
Muller Florian,
Richardson Arlan,
Van Remmen Holly
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a818-d
Subject(s) - sod1 , atrophy , oxidative stress , medicine , endocrinology , hindlimb , muscle atrophy , skeletal muscle , superoxide dismutase , chemistry
The purpose of the present study is to investigate the effect of CuZnSOD absence on oxidative stress and skeletal muscle atrophy with age using CuZnSOD homozygous knockout mice (Sod1−/−). Oxidative damage to DNA (8oxodG), lipid peroxidation (F2‐isoprostanes), and protein (carbonyls) was 130%, 60%, and 49% higher respectively in young Sod1−/− (4–6 mo) compared to young WT. Muscle atrophy in hindlimb of Sod1−/− was significant, reaching 45% in old Sod1−/− (20–23 mo) and even in young Sod1−/− (20%) compared to age‐matched WT. In terms of individual muscle loss, muscles that are composed of predominantly fast type II fibers including the gastrocnemius (37%) and plantaris (39%) were affected, while the mass of soleus (type I) was not changed. To see if the muscle atrophy is associated with a functional decline and impact motor behavior of the Sod1−/−, voluntary wheel running activity and Rota‐rod performance were measured. Young Sod1−/− exhibited a significant decrease (42%) in voluntary wheel running activity compared to age‐matched WT. At 12 to 15 months of age a significant (p<0.0001) reduction in Rota‐rod performance was observed in Sod1−/− compared to WT. In addition, hindlimb tremor was apparent in almost all in old Sod1−/− and some Sod1−/− also showed gait abnormalities. In summary, Sod1−/− exhibited significant acceleration of age‐related skeletal muscle atrophy and increased oxidative damage that are associated with motor behavioral abnormalities evident in young Sod1−/− and progressively deteriorated with age. Thus, these data suggest that the absence of CuZnSOD imposes significant oxidative stress concomitant with muscle atrophy and neuromuscular abnormalities.