Age-related changes of mitochondrial DNA content and mitochondrial genotypic and phenotypic alterations in rat hind-limb skeletal muscles.

Mitochondrial DNA (mtDNA) content relative to nuclear DNA content as well as mitochondrial transcription factor A (TFAM) content was measured in four hind-limb skeletal muscles, namely soleus (S), tibialis anterior (TA), gastrocnemius (G), and extensor digitorum longus (EDL) of adult rats. Content of mtDNA in 6-month-old rats is in the rank order of S > TA > G > EDL, and TFAM content is higher in S than in the other studied muscles. After the rat is 6 months of age, the mtDNA content decreases only in S and TA, whereas the TFAM content increases only in S. Deletions in mtDNA appear quite early in life in S and later on in the other muscles. Fibers defective for mitochondrial respiratory enzymes appear in rats at 15 months of age. In the oldest animals, the highest frequencies of occurrence of mtDNA deletions as well as of mitochondrial phenotypic alterations are found in S according to its highest mtDNA content and oxidative potential.