degradation is mediated through the ubiquitin-proteasome pathway. To
investigate if altered proteasome activity plays a role in age-related muscle
atrophy, we examined muscle size and proteasome function in young and aged
F344BN rats. Significant age-related muscle atrophy was confirmed by the 38%
decrease in cross-sectional area of type 1 fibers in soleus muscle.
Determination of proteasome function showed hydrolysis of fluorogenic peptides
was equivalent between ages. However, when accounting for the 3-fold increase
in content of the 20S catalytic core in aged muscle, the lower specific
activity suggests a functional loss in individual proteins with aging.
Comparing the composition of the catalytic beta-subunits showed an age-related
4-fold increase in the cytokine-inducible subunits, LMP2 and LMP7.
Additionally, the content of the activating complexes, PA28 and PA700, relative
to the 20S proteasome was reduced 50%. These results suggest significant alterations
in the intrinsic activity, the percentage of immunoproteasome, and the
regulation of the 20S proteasome by PA28 and PA700 in aged muscle.
PMID: 14678786 [PubMed - indexed for MEDLINE]