Aging and dietary restriction alter proteasome biogenesis and composition in the brain and liver

Interventions such as dietary restriction (DR) have been reported to ameliorate age-related proteasome inhibition in some tissues. Currently it is not known what effects aging and DR have on proteasome biogenesis in the liver and brain, nor have previous studies identified the links between changes in proteasome composition, biogenesis, and activity in the aging brain and liver. In the present study we demonstrate that the brain and liver exhibit age-dependent decreases in 26S and 20S proteasome activity. Additionally, our studies demonstrate that the brain and liver undergo selective changes in proteasome biology, including increases in proteasome biogenesis in response to aging and DR, with the liver exhibit more robust plasticity as compared to the brain. Lastly, studies demonstrated that aging and DR alter the interaction of Hsp90 with the 20S proteasome complex in the brain and liver. These studies affirm the dynamic nature of the proteasome complexes in both the liver and brain following aging and DR. Additionally, these data indicate that the relationship between proteasome composition/biogenesis and proteasome activity in tissues is extremely complex and tissue specific. These data have implications for understanding the effects of tissue specific effects of aging and DR on protein turnover and proteotoxicity.