Altered proteasome function and subunit composition in aged muscle

Aimee D. Husom, Elizabeth A. Peters, Erin A. Kolling, Nicole A. Fugere, La Dora V. Thompson, Deborah A. Ferrington

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143 Scopus citations


Myofibrillar protein 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 β-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.

Original languageEnglish (US)
Pages (from-to)67-76
Number of pages10
JournalArchives of Biochemistry and Biophysics
Issue number1
StatePublished - Jan 1 2004

Bibliographical note

Funding Information:
This work was supported by the American Federation for Aging Research (D.A.F.) and the National Institute of Aging Grants AG17768 and AG21626 (L.V.T.). The antibody to the S4 subunit of PA700 was kindly provided by Dr. George DeMartino. We thank Janice Shoeman for her assistance with muscle processing. Aaron Berg, Lori Boyer, Betsy Cionca, and Adam Smith assisted with the data on cross-sectional area of the soleus muscle.

Copyright 2017 Elsevier B.V., All rights reserved.


  • Aging
  • Muscle atrophy
  • PA28
  • PA700
  • Proteasome
  • Proteasome subunits
  • Sarcopenia
  • Skeletal muscle

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