title: Beneficial effects of mild lifelong dietary restriction on skeletal muscle: prevention of age-related mitochondrial damage, morphological changes, and vulnerability to a chemical toxin.
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, 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.
authors.affiliation: Department of Clinical Medicine, National Institute for Minamata Disease, 4058-18 Hama, 867-0008, Minamata, Japan. usuki@nimd.go.jp
authors.forename: Fusako
authors.initials: F
authors.lastname: Usuki
authors.forename: Akira
authors.initials: A
authors.lastname: Yasutake
authors.forename: Fujio
authors.initials: F
authors.lastname: Umehara
authors.forename: Itsuro
authors.initials: I
authors.lastname: Higuchi
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D003459:Crystallins / Q000378:metabolism; D004032:Diet; D005508:Food Deprivation / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008628:Mercury / Q000378:metabolism / Q000633:toxicity*; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology*; D009243:NAD / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D003459:Crystallins; D006360:Heat-Shock Proteins; D009243:NAD; C024829:8-hydroxyguanine; D006147:Guanine; D002374:Catalase; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D008628:Mercury