Stability of the nuclear protein turnover during cellular senescence of human fibroblasts

SPECIFIC AIMSAccumulation of oxidized proteins and a loss of activity of the proteolytic enzymes, including the proteasome, are highlights of age-related changes of cellular metabolism. We tested whether cytosolic and nuclear proteasomes are equally affected by age-related changes and whether the proteasomal system is able to remove oxidized proteins from both compartments.PRINCIPAL FINDINGS1. Protein turnover and proteasomal activity in the nucleus of MRC-5 fibroblasts is stable during senescenceIn a first series of experiments we tested the overall turnover of proteins in the cytosol and the nucleus of young and senescent cells. As shown in Fig. 1⤻ , overall protein degradation declines dramatically during proliferative senescence. Nuclear proteins turn over significantly slower than the total protein pool. But in disagreement with the total degradation rates, nuclear proteins seem to turn over much faster in senescent fibroblasts. Therefore, it can be concluded that the nuclear protein turnover is stab...