Cellular phenotypes of age-associated skeletal muscle mitochondrial abnormalities in rhesus monkeys

Rhesus monkey vastus lateralis muscle was examined histologically for age-a ssociated electron transport system (ETS) abnomlalities: fibers lacking cyt ochrome c oxidase activity (COX-) and/or exhibiting succinate dehydrogenase hyperreactivity (SDH++). Two hundred serial cross-sections (spanning 1600 mu m) were obtained and analyzed for ETS abnormalities at regular intervals . The abundance and length of ETS abnormal regions increased with age. Extr apolating the data to the entire length of the fiber, up to 60% of the fibe rs were estimated to display ETS abnormalities in the oldest animal studied (34 years) compared to 4% in a young adult animal (11 years). ETS abnormal phenotypes varied with age and fiber type. Middle-aged animals primarily e xhibited the COX- phenotype, while COX-/SDHC++ abnormalities were more comm on in old animals. Transition region phenotype was affected by fiber type w ith type 2 fibers first displaying COX- and then COX-/SDH++ while type 1 fi bers progressed from normal to SDH++ and then to COX-/SDH++. in situ hybrid izations studies revealed an association of ETS abnormalities with deletion s of the mitochondrial genome. By measuring cross-sectional area along the length of ETS abnormal fibers, we demonstrated that some of these fibers ex hibit atrophy. Our data suggest mitochondrial (mtDNA) deletions and associa ted ETS abnormalities are contributors to age-associated fiber atrophy. (C) 3000 Elsevier Science B,V, All rights reserved.