ER stress and hormetic regulation of the aging process.

An ability to mount a stress resistance under pressure is a major host defence mechanism and has been a fundamental force during evolution. However, the adaptation capacity clearly declines during aging and this loss of stress resistance accelerates the aging process exposing the organism to degenerative diseases. The effect of stress on organisms seems to be a dose-dependent response, i.e. mild stress induces a stress tolerance and extends the lifespan whereas excessive stress accentuates the aging process. This paradox is known as hormesis in aging research. It is essential to distinguish the intensity of cellular stress and thus mount an appropriate host defence. The endoplasmic reticulum (ER) contains three branches of stress transducers, i.e. IRE1, PERK, and ATF6 pathways, all of which recognize stress-related disturbances in the function of ER. These transducers trigger a complex signaling network which activates an unfolded protein response (UPR). Interestingly, ER stress transducers can distinguish the intensity of ER stress and induce a dose-dependent UPR, either adaptive response to stress or apoptotic cell death. The efficiency of the stress recognition system and UPR signaling declines during aging. We will discuss the role of ER stress in hormetic regulation of aging process and longevity. 2010 Elsevier Ireland Ltd. All rights reserved.