Rocket worm: Hypergravity activates DAF-16

Here’s an article I’ve been sitting on for a while without really knowing what to do with it: The activity of DAF-16, a transcription factor that is essential for the life-extension benefits of IGF-1 signaling mutations in the worm C. elegans, appears to be modulated by hypergravity. From Kim et al.:

Gravity Force Transduced by the MEC-4/MEC-10 DEG/ENaC Channel Modulates DAF-16/FoxO Activity in Caenorhabditis elegans

The gravity response is an array of behavioral and physiological plasticity elicited by changes in ambient mechanical force and is an evolutionarily ancient adaptive mechanism. We show in Caenorhabditis elegans that the force of hypergravity is translated into biological signaling via a genetic pathway involving three factors: the degenerin/epithelial Na+ channel (DEG/ENaC) class of mechanosensory channels of touch receptor neurons, the neurotransmitter serotonin, and the FoxO transcription factor DAF-16 known to regulate development, energy metabolism, stress responses, and aging. After worms were exposed to hypergravity for 3 hr, their muscular and neuronal functions were preserved, but they exhibited DAF-16::GFP nuclear accumulation in cells throughout the body and accumulated excess fat. Mutations in MEC-4/MEC-10 DEG/ENaC or its partners MEC-6, MEC-7, and MEC-9 blocked DAF-16::GFP nuclear accumulation induced by hypergravity but did not affect DAF-16 response to other stresses. We show that exogenous serotonin and the antidepressant fluoxetine can attenuate DAF-16::GFP nuclear accumulation in WT animals exposed to hypergravity. These results reveal a novel physiological role of the mechanosensory channel, showing that the perception of mechanical stress controls FoxO signaling pathways and that inactivation of DEG/ENaC may decouple mechanical loading and physiological responses.

Outside of completely artificial settings (like centrifuges and spacefaring vehicles), hypergravity is one stress that I’m fairly sure worms never, ever encounter. Because this stress response involves mechanosensory neurons, I’m guessing that it evolved as a way of dealing with increases in ambient shear force or pressure (e.g. if the worm is in soil that is getting smooshed by an elephant, or accidentally finds itself under a lot of water).

I’m still not really sure what to make of it. I share it primarily because it connects two of my favorite things (space travel and biogerontology), and also because it has a somewhat surprising result: who would have guessed that hypergravity would have the same effect as life-extending mutations?