A Role for UNC-45 in Maintaining Myosin During Aging

Using immunostaining with antibodies to myosin heavy chain A (MHC A), we show that there is a gradual decline in motility beginning at day 4 and the number of A-bands (a measure of thick filament assembly) beginning at day 8 adults. By day 12 and especially day 16, there is also disorganization of A-bands. This disorganization appears similar to that of unc-45 ts mutants grown at the restrictive temperature. We have found that in C. elegans a decline in hsp-90 mRNA (day 2) directly precedes a decline in HSP-90 protein (day3), which directly precedes a decline in UNC-45 protein (day4), which then in turn precedes a decline in Myosin B (day8), the main client of UNC-45. unc-45, unc-54, and myo-3 mRNA decline immediately after reaching maturity (day 1) and remain stable, though low – which is expected for proteins assembled into the sarcomere. We also observe a decrease in UNC-45 protein, but not mRNA, in an hsp-90 loss of function mutant, suggesting a role for HSP-90 in UNC-45 regulation and/or protein stabilization. We also observe early onset of sarcopenia when UNC-45 is lost during adulthood and an increase in an unknown UNC-45 post translational modification with age.