Oxygen-sensing circuit extends lifespan in worms
The body has an emergency programme for low oxygen conditions. In worms, activating that programme in a targeted way can extend lifespan. Researchers have now identified exactly which nerve cells are responsible.
When cells receive too little oxygen, they activate a protective network of responses. This is called the hypoxic response. In the roundworm Caenorhabditis elegans, genetically activating this system extends lifespan. But which cells and signals are needed was not yet clear.
The researchers activated the low-oxygen protein HIF-1 in specific nerve cells. They found that HIF-1 activity in a particular type of serotonin-producing neuron was both necessary and sufficient to extend the worms’ lifespan. Serotonin is a signalling molecule that relays information to other cells in the body.
The circuit, step by step
From the serotonin-producing neurons, the signal travels to a second type of nerve cell, the RIS interneurons, via the serotonin receptor SER-7. The neurotransmitter GABA, tyramine, and a neuropeptide called NLP-17 were also part of the circuit. Finally, oxygen- and carbon dioxide-sensing cells act downstream of HIF-1 in this circuit.
The study shows that the longevity effect of the hypoxic response does not need to operate throughout the body simultaneously. A specific neural circuit seems to coordinate it. The authors point to this as a potential lead for targets in mammals, while stressing that effects in worms cannot be directly translated to humans. The study was published in eLife.
Why this matters
Until now, research on the hypoxic response focused on direct cellular effects. This work shows the nervous system can act as a coordinator. That is a different entry point for understanding how stress responses influence lifespan. Translation to humans requires further research.
Search terms to explore further: HIF-1 lifespan neurons, hypoxic response C. elegans longevity, serotonin neural circuit aging