Age-associated changes in rat skeletal muscle mitochondria

The oxidative stress theory of aging states that mitochondria produce and are damaged by reactive oxygen species. Oxidatively damaged macromolecules accumulate and are responsible for physiological declines seen with aging. Two studies were undertaken to examine age-associated alterations of skeletal muscle mitochondria.; COX (cytochrome c oxidase, complex IV of the electron transport system) activity and levels of COX protein subunits I and IV as well as COX I mRNA were measured in three skeletal muscles of male (F344 X BN) F{dollar}sb1{dollar} rats from 5- to 38-months of age. The adductor longus (ADL) and soleus (composed primarily of slow oxidative fibers (type I)), both displayed significant decreases in COX activity (per milligram of crude mitochondrial preparation protein) with age. COX activity in the extensor digitorum longus (composed primarily of fast oxidative glycolytic and fast glycolytic fibers (type 11a and b, respectively)), did not change with age. Significant declines occurred with age in the steady-state levels of both COX I and COX IV subunits in the soleus. COX activity per microgram of COX I subunit protein did not change with age in the three muscles. Total protein yield in the crude mitochondrial preparations from whole muscle increased from the soleus with age. The levels of COX I mRNA did not change with age in the three muscles examined. These data may be interpreted as resulting from a large accumulation of damaged mitochondria in the soleus, such as that seen in ragged red fibers.; Mitochondrial DNA (mtDNA) deletion accumulation was investigated in muscles from male Lobund-Wistar rats subjected to caloric restriction (CR) in late middle-age (17 months). ADL, soleus, EDL and epitrochlearis (composed of predominantly type II fibers) from 3- to 4-month old ad libitum fed and 30- to 32-month old control and CR animals (restricted by 35% and 50%, designated CR{dollar}sb{lcub}35{rcub}{dollar} and CR{dollar}sb{lcub}50{rcub}{dollar} respectively) were studied. Multiple mtDNA deletions accumulated in all four skeletal muscles with age. CR{dollar}sb{lcub}50{rcub}{dollar} animals had significantly lower numbers of deletion products in the ADL and soleus as compared to CR{dollar}sb{lcub}35{rcub}{dollar} animals.; The results of both studies demonstrate differences in mitochondrial responses to aging among the muscles examined.