Regulation of skeletal muscle mitochondrial content during aging.

Mitochondrial content of skeletal muscle varies among fiber types, and changes in complex ways during aging. We evaluated the regulatory origins of differences in mitochondrial content among muscles of varied fiber type in F344xBNF1 rats, and how these regulatory patterns are altered with aging. In adult (12 month) animals we found that units citrate synthase (CS)/g tissue, a marker for mitochondrial content, varied approximately 3-fold among 10 skeletal muscles. Stoichiometric relationships between CS and isocitrate dehydrogenase, aconitase, and cytochrome c oxidase were generally preserved across fiber types. Among the 10 muscles of adult rats, CS content correlated with nuclear content (R2= 0.36). Muscles differed widely in CS messenger RNA (mRNA)/DNA (an index of variation in transcriptional regulations) and units CS/CS mRNA (an index of variation in posttranscriptional regulations). All muscles of aged rats (35 months) showed an increase in mg DNA/g, suggestive of atrophy. Age-dependent declines in units CS/DNA were accompanied by reductions in CS mRNA/DNA and/or units CS/CS mRNA, depending on muscle fiber type. Thus, declines in units CS/DNA with age appeared to be due to transcriptional as well as translational variations. Differences in mitochondrial content among muscle fiber types and age groups may arise from variations in nuclear content and posttranscriptional processes, as well as transcriptional regulation.