Further Exploring How the Hypoxic Response Slows Aging
Cells respond to a broad range of various stresses in quite similar ways. Cold, heat, lack of nutrients, lack of oxygen, presence of toxins, irradiation, and so forth, may all have different sensors and initial responses, but these responses converge on an increase in maintenance and repair processes - such as autophagy. When stress and consequent damage and dysfunction is mild, this increased maintenance and repair produces a net benefit. Repeated or constant mild stresses can thus modestly slow aging by making cells more resilient to the forms of damage and dysfunction that arise in later life.
A coordinated response to stress is crucial for promoting the short-term and long-term health of an organism. The perception of stress, frequently through the nervous system, can lead to physiological changes that are fundamental to maintaining homeostasis. Activating the response to low oxygen, or hypoxia, extends healthspan and lifespan in the nematode worm C. elegans. However, despite some positive impacts, negative effects of the hypoxic response in specific tissues prevent translation of their benefits in mammals. Thus, it is imperative to identify which components of this response promote longevity.
Here, we interrogate the cell-nonautonomous hypoxic response signaling pathway. We find that HIF-1-mediated signaling in ADF serotonergic neurons is both necessary and sufficient for lifespan extension. Signaling through the serotonin receptor SER-7 in the GABAergic RIS interneurons is necessary in this process. Our findings also highlight the involvement of additional neural signaling molecules, including the neurotransmitters tyramine and GABA, and the neuropeptide NLP-17, in mediating longevity effects. Finally, we demonstrate that oxygen- and carbon-dioxide-sensing neurons act downstream of HIF-1 in this circuit.
Together, these insights develop a circuit for how the hypoxic response cell-nonautonomously modulates aging and suggests valuable targets for modulating aging in mammals.
Studying hypoxia by breading worms that mimic hypoxia seems dubious to me.