Enhanced Lipophagy via the Unfolded Protein Response in Neurons Modestly Extends Life in Nematodes

Researchers here show a small effect on life span in nematode worms resulting from an increase in the unfolded protein response in the endoplasmic reticulum in neurons. This is connected with lipophagy, a process that depletes lipids in these cells. In this context, it is worth mentioning that, as a general rule, small effect sizes in nematodes are not interesting from the perspective of producing therapies to extend healthy life for mammals. Short-lived species have life spans that are very plastic in response to environment circumstances and changes in the regulation of cellular housekeeping processes. Longer lived species exhibit far lesser changes in life span under the same circumstances. So a small effect size in nematodes will likely be indistinguishable in humans. The homeostatic regulation of protein folding (proteostasis), which is monitored in specific subcellular compartments, is an integral player in stress resistance and longevity. The endoplasmic reticulum (ER), in particular, is a central regulator of stress monitoring as it controls nearly a third of the cell's proteins, provides an internal medium for lipid homeostasis and cell signaling, and communicates directly with all other organelles to maintain cellular secretion. Thus, cells have evolved numerous quality control machineries dedicated to protecting the ER both under basal and stressed conditions. Notably, the ER has evolved three primary branches of its unfolded protein response (UPRER...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs