Significance
Cells and organisms grow old and die. We develop a biophysical model of the mechanism. Young cells are kept healthy by the positive processes of protein synthesis, degradation, and chaperoning (the activity of keeping proteins properly folded). But, with age, negative processes increase: Oxidative damage accumulates randomly in the cell’s proteins, healthy synthesis and degradation slow down, and—like overfilled garbage cans—chaperone capacity is exceeded. The chaperones are distracted trying to fold irreversibly damaged proteins, leading to accumulating misfolded and aggregated proteins in the cell. The tipping point to death happens when the negative overwhelms the positive. The model makes several quantitative predictions of the life span of the worm
Caenorhabditis elegans
.