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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

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Abstract

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, αβ 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.

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Acknowledgments

We thank Professor Toru Iwaki, Kyushu University School of Medicine, for his kind gift of anti-αβ crystallin antibody. We also wish to thank Mr. Hidefumi Nishiyama for his helpful animal care and Ms. Noriko Hirata and Ms. Yuko Shirahama for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Clinical Medicine, National Institute for Minamata Disease, 4058-18 Hama, 867-0008, Minamata, Japan

    Fusako Usuki

  2. Biochemistry Section, National Institute for Minamata Disease, 4058-18 Hama, 867-0008, Minamata , Japan

    Akira Yasutake

  3. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, 890, Kagoshima , Japan

    Fujio Umehara & Itsuro Higuchi

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  1. Fusako Usuki
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  2. Akira Yasutake
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  3. Fujio Umehara
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  4. Itsuro Higuchi
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Correspondence to Fusako Usuki.

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Usuki, F., Yasutake, A., Umehara, F. et al. Beneficial effects of mild lifelong dietary restriction on skeletal muscle: prevention of age-related mitochondrial damage, morphological changes, and vulnerability to a chemical toxin. Acta Neuropathol 108, 1–9 (2004). https://doi.org/10.1007/s00401-004-0844-0

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  • DOI: https://doi.org/10.1007/s00401-004-0844-0

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