Does Caloric Restriction Affect Electron Transport System Abnormalities?





S. H. McKiernan, E. A. Bua and J. M. Aiken

University of Wisconsin, Department of Animal Health and Biomedical Sciences, 1656 Linden Dr., Madison, WI 53706



Electron transport system (ETS) abnormalities occur in mitochondria of non-replicative tissues, such as brain and skeletal muscle, as part of the aging process. The molecular basis for these abnormalities involves mutations in mitochondrial DNA (mtDNA). Deletion mutations remove genes encoding critical sub-units required by the ETS resulting in a cytochrome c oxidase negative (COX-) and succinate dehydrogenase hyper-reactive (SDH++) phenotype. Associated with ETS abnormal regions is intra-fiber atrophy. We have proposed that this atrophy is a cause of fiber loss thus contributing to sarcopenia: the progressive muscle mass loss with age. An intervention that reduces the pace of sarcopenia in aged mammals is caloric restriction. The purpose of this study was to determine whether early on-set caloric restriction affects the accumulation and characteristics of electron transport system abnormalities found in skeletal muscle fibers of aged rats.

Two groups of aged (36-month) Fischer Brown Norway hybrid rats were used in this study. One group was maintained on a 40% calorie restricted diet beginning at 14 weeks (n=7), the other group were fed ad libitum (n=6). Serial sections of the largest quadriceps muscles (rectus femoris and vastus lateralis) were examined for COX and SDH enzyme activity. ETS abnormal fibers were located and followed through 1000 - 2000 microns to determine the abundance and the length of these abnormalities. The cross-sectional area (CSA) of normal and abnormal fibers was measured at 70µ intervals. A CSA ratio was calculated for each fiber, where the minimum CSA in the abnormal region was divided by the mean CSA of the normal region.

A total of 177 RRF were observed in the rectus femoris and vastus lateralis muscles of ad libitum fed rats, whereas only 36 RRF were observed in the same muscles of calorie restricted rats. The mean number of RRF per animal was significantly different between the two treatment groups. The mean length of ETS abnormalities in ad libitum rats was 426µm, and 409µm for calorie restricted, values were not significantly different. The mean CSA ratio for abnormal fibers was the same between ad libitum and calorie restricted rats, however, the CSA ratio for ETS abnormal fibers was significantly lower than the CSA ratio of normal fibers in either restricted or ad libitum rats. There was a significant negative correlation between ETS abnormality length and CSA ratio in both ad libitum and calorie restricted rats demonstrating that fibers with longer ETS abnormalities were more likely to have smaller CSA ratios.

Caloric restriction had a significant negative effect on the number of ETS abnormalities in the quadriceps muscles of aged hybrid rats, however, restriction did not affect the length or cross-sectional area of an ETS abnormal region once established. Thus calorie restriction affects the onset and not the progression of electron transport system abnormalities.

This work was supported by RO1 AG11604 and RO1 AG17543 from the NIH.




Key words: calorie restriction, electron transport system abnormalities







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