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Beneficial effects of mild lifelong dietary restriction on skeletal muscle: prevention of age-related mitochondrial damage, morphological changes, and vulnerability to a chemical toxin

The effect of mild lifelong dietary restriction (DR) on age-related changes was investigated in rats. Histopathological findings were compared between 25-month-old male rats fed ad libitum and 25-month-old male rats that were calorie restricted (80% of ad libitum calories; protein 15%) from 9 weeks...

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Bibliographic Details
Published in:Acta neuropathologica 2004-07, Vol.108 (1), p.1-9
Main Authors: Usuki, Fusako, Yasutake, Akira, Umehara, Fujio, Higuchi, Itsuro
Format: Article
Language:English
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Summary:The effect of mild lifelong dietary restriction (DR) on age-related changes was investigated in rats. Histopathological findings were compared between 25-month-old male rats fed ad libitum and 25-month-old male rats that were calorie restricted (80% of ad libitum calories; protein 15%) from 9 weeks of age. DR-fed rats retained motor activity even in old age compared with ad libitum-fed rats. Histopathological studies on soleus muscles clarified myopathic changes in the ad libitum-fed rats, including variations in fiber size and an increase in the number of central nuclei. Increased non-grouping atrophic angulated fibers were also observed. The specimens revealed a confused arrangement of the mitochondria and decreased mitochondrial electron transduction enzyme activities, indicating mitochondrial insults in the ad libitum-fed rats. In contrast, no myopathic changes, little mitochondrial insult, and fewer angulated fibers were recognized in the DR-fed rats. The accumulations of heme oxygenase-1, alphabeta crystallin, 8-hydroxydeoxyguanosine, and heat shock protein 27 were recognized in ad libitum-fed rats, indicating the attack of oxidative stress. In contrast, the expressions of these proteins were suppressed in DR-fed rats. The results suggest that even mild calorie restriction is enough to attenuate oxidative stress and age-related morphological changes in skeletal muscle. Additionally, DR was effective in protecting against methylmercury-induced pathological changes. Small fiber size and suppression of mitochondrial electron transduction enzyme activities in skeletal muscle and degenerative changes in peripheral nerves were milder in methylmercury-exposed DR-fed rats. The results indicate that mild lifelong DR also protects skeletal muscle and peripheral nerves against a chemically-induced form of oxidative stress.
ISSN:0001-6322
1432-0533
DOI:10.1007/s00401-004-0844-0