Water Loss in Aging Erythrocytes Provides a Clue to a General Mechanism of Cellular Senescence

Experimental evidence for age-dependent loss of intracellular water content as a widespread concomitant of cellular senescence is reviewed. Quantitative models are presented, indicating that an age-dependent increase in macromolecular crowding resulting from water loss may be responsible for three observed phenomena: a general age-dependent loss of intracellular protein solubility, a delayed and rapid appearance of high molecular weight aggregates, and an age-dependent transfer of intracellular protein from dilute to concentrated or condensed phases.