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C. A. McMullen, F. H. Andrade; Altered Transcriptome and Functional Deficits in Aging Rodent Extraocular Muscles. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5622.
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© ARVO (1962-2015); The Authors (2016-present)
The fast and constant activity of the extraocular muscles (EOMs) imposes mechanical and metabolic stresses not usually seen in other skeletal muscles. Its extreme functional profile may influence the way EOMs change with age. In this study, we tested the hypothesis that aging impairs the functional properties and changes the transcriptome of rat EOMs.
We isolated EOMs and extensor digitorum longus (EDL) muscle bundles from 6- and 30-mo old male Fischer 344-Brown Norway rats for gene expression profiling using cDNA microarrays, morphometric analysis of muscle cryosections, and isometric contractile properties and fatigue resistance in vitro.
EOM mean fiber area decreased by ~24% from 6 to 30-mo of age (481±309 to 367±176 sq. µm respectively, mean±SD, P < 0.01). Aging had a significant effect on force production by EOMs: peak twitch and tetanic forces per sq. cm decreased 12±2 and 23±2% by 30-mo, respectively (P < 0.05 vs. forces obtained at 6-mo). In addition, EOMs from 30-mo rats fatigued faster than at 6-mo: endurance decreased from 600 to 532±19 seconds (6- vs. 30-mo, P< 0.01) and residual force decreased from 67±3 to 53±6% of initial force (6- vs. 30-mo, P< 0.01). The effects of age on EOM gene expression profile were complex. At 6-mo, 705 genes and expressed sequence tags (ESTs) were differentially expressed in EOMs compared to EDL (436 up, 269 down). Overall, the EOM profile at this age was mostly consistent with the increased expression of fetal, developmental and EOM-specific myosin isoforms, enzymes involved in glycolysis and Krebs cycle, and ion transporters and pumps. At 30-mo EOMs had 655 differentially expressed genes and ESTs (480 up, 175 down), with a profile consistent with ongoing tissue remodeling.
These results support our original hypothesis that aging significantly alters the trascriptome and function of rat EOMs. In addition, the loss of endurance and gene expression changes suggest that the metabolic capacity of EOMs decreases with age.
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