Midnight munchers: starved worms can’t sleep
Food-deprivation inhibits the stress-induced sleep response in C. elegans.
For many animals, the essential physiological drives of sleep and food are intimately linked. You might have noticed this if you’ve ever stayed up far too late and found yourself craving a snack. Yet because it’s impossible for most animals to eat and sleep at the same time, these two biological necessities must compete with each other. In GENETICS, Goetting et al. report what happens when the need for sleep and the need for food come into direct conflict in the model nematode Caenorhabditis elegans.
When C. elegans is exposed to a stressful condition like high heat or UV radiation, it goes into a quiescent state called stress-induced sleep (SIS). Sleeping worms cease moving and feeding, and they barely respond to normally unpleasant stimuli—unless they are rudely awoken by a sharp poke.
In contrast, the authors found that food-deprived worms were less prone to this stress-induced snooze than their well-fed counterparts. This was true regardless of whether there was more food around to forage for; that is, the worms tended to remain active after stress whether or not they were provided with additional food after being starved.
The authors also found that starvation-induced sleep-suppression was enhanced when there were more worms on the plate. This makes sense, because higher population densities mean fewer resources, so seeking food instead of going to sleep is likely the better option. Interestingly, crowding only inhibited SIS when worms were starved; well-fed worms in crowded plates showed no change in SIS after stress treatment.
Insulin signaling and TGF-β signaling play major roles in sensing food availability in C. elegans, so the authors asked whether these pathways play a role in SIS under normal conditions. They found that worms with mutations in a TGF-β ligand, but not the insulin receptor, had impairments in SIS. Further investigation revealed that TGF-β involvement in SIS is downstream of the ALA neuron (a master neural regulator of SIS) and dependent on the gene DAF-3, which is involved in TGF-β signaling.
If this DAF-3-dependent pathway was necessary and sufficient for food-deprivation-induced inhibition of SIS, it would follow that worms lacking DAF-3 would have no trouble falling asleep after being starved and stressed—but when the authors tested this, they instead found that the DAF-3 mutants had the same response as wild-types: they stayed awake. Therefore, the authors conclude that although the TGF-β pathway plays a role in normal SIS, it is not solely responsible for the lack of SIS when worms are starved. Consistent with this notion, the authors uncovered evidence that the TOR signaling pathway, which is active when nutrients are available and promotes growth and protein synthesis, plays a role in starvation-induced sleep suppression as well.
Since sleep deprivation can be deadly, the authors tested whether food deprivation affected how much the worms needed to sleep to stay alive. They found that worms that were deprived of food, stressed, and then kept awake survived better than worms that were just stressed and kept awake. Thus, starving the worms allowed them to stay awake, at least in part, because they needed their sleep less.
Food-Dependent Plasticity in Caenorhabditis elegans Stress-Induced Sleep Is Mediated by TOR–FOXA and TGF-b Signaling