FIGURE 1.

Proteostatic changes in aged vs. young cells. When faced with misfolded proteins, young cells demonstrate relatively low ER stress, high chaperone efficiency and stress tolerance, and primarily adaptive UPR signaling. This generally leads to a resolution of the misfolded proteins and therefore, ER stress. In contrast, aged cells are more likely to accumulate these misfolded proteins (partially due to loss of chaperone protein efficiency), leading to a state of ER stress, which they are less able to resolve. Their lower stress tolerance eventually leads to a relative increase in apoptotic UPR signaling over adaptive, ultimately causing cell death.