Fig. 2.

In cell aging, oxidative damage leads to increased misfolding and aggregation, which eventually causes cell death. (A) The age-dependent slowing of synthesis and degradation causes the accumulation of damaged (black line), misfolded (orange line), and aggregated (red line) states and depletion of the native (blue line) state. Progressive cell aging causes proteostasis to transition through 2 phases: 1) the progressive titration of chaperones by damaged proteins, causing the accumulation of misfolded protein, followed by 2) misfolded proteins crossing their solubility threshold, triggering late-life aggregation (the region inside the vertical dashed lines). (B) The gradual increase of protein damage with age in different organisms, as measured by carbonyl content. The black line indicates the percentage of damaged protein predicted by the current model. (C) Age-dependent mortality rate data at T = 20.1 ^○C (red symbols). The black line is the theoretical fit to the data. (D) Predicted survival curve in wild-type Caenorhabditis elegans at T = 20 ^○C. The vertical dashed line shows the point of 50% survival and is taken as the average life span of the organism.