Proteostasis collapse, inter-tissue communication and the regulation of aging at the organismal level

The ongoing debate of whether the aging process is driven by stochastic events or regulated by biological mechanisms is nearly a century old. While numerous studies strongly support the idea that signaling and metabolic pathways govern the pace of aging, other findings suggest that a sequence of stochastic events underlies the progression of this process. Two recent developments in the field of aging provide affirmation to the notion that aging has regulated aspects. First, the collapse of proteome integrity (proteostasis), a prominent aspect of aging, occurs within a surprisingly narrow time window, shortly after transition of the nematode Caenorhabditis elegans to adulthood. In addition, inter-tissue communication was found to play key roles in proteostasis maintenance across tissues and to affect the worm's lifespan. Here we briefly review the current knowledge in the field and delineate the experimental evidence which indicates that aging is a complex, multi-factorial process whose pace is determined by both random events and regulatory mechanisms.