Dietary restriction improves proteostasis and increases life span through endoplasmic reticulum hormesis.

ABSTRACT: Unfolded protein response (UPR) of the endoplasmic reticulum (UPR^ER) helps maintain proteostasis in the cell. The ability to mount an effective UPR^ER to external stress (iUPR^ER) decreases with age and is linked to the pathophysiology of multiple age-related disorders. Here, we show that a transient pharmacological ER stress, imposed early in development on Caenorhabditis elegans, enhances proteostasis, prevents iUPR^ER decline with age, and increases adult life span. Importantly, dietary restriction (DR), that has a conserved positive effect on life span, employs this mechanism of ER hormesis for longevity assurance. We found that only the IRE-1-XBP-1 branch of UPR^ER is required for the longevity effects, resulting in increased E

SUBMITTER: Matai L 

PROVIDER: S-EPMC6717303 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature