The takeaway here is that we need to look at the bigger picture: mechanisms that maintain oxygen homeostasis must operate over a very wide range of oxygen concentrations, and in response to temporal challenges that span from seconds (for example, in the dynamic control of respiration) to days, weeks or months (for example, in metabolic and developmental adaptation).įurthermore, some of the most exciting applications of this research today are in cancer. So in a way you could say that the HIF are the master regulators of oxygen homeostasis.Īnother important insight we can glean from Kaelin, Ratcliffe and Semenza is that hypoxia does not equate to a specific oxygen concentration, since many tissues function physiologically at levels equivalent to an atmosphere of 5% oxygen, some even at levels as low as 1% oxygen. These target genes act as a switch to produce EPO, which is needed to match O2 supply and demand. The HIFs bind to hypoxia-inducible elements (HIE) in hundreds, possibly even thousands of target genes.
They do not have long survival rates in high-oxygen conditions. These HIF accumulate within cells under hypoxic conditions, i.e. Within this feedback loop, we also find a specific class of proteins, the so-called HIF (hypoxia-inducible factors). Therefore, EPO is part of a highly sensitive feedback loop that controls red blood cell production in response to changes in blood oxygen availability. (This is also why some endurance athletes use EPO for doping- it increases their supply of oxygen-carrying red blood cells).
Increased levels of red blood cells affect O2 availability in the body because red blood cells are responsible for the transport of O2 from the lungs to all body tissues. EPO itself increases the production of oxygen-carrying red blood cells. These genes increase levels of erythropoietin (EPO)- a protein that is synthesized by the kidneys and, to a lesser extent, the liver. But it has also been rejected multiple times by top journals, prior to being accepted for publication.) (As an interesting aside in terms of scientific discoveries and their impact: Semenza's seminal scientific paper has been cited thousands of times. One can trace this back to the beginning of the 1990s, when Semenza identified genes that turned on if oxygen levels are low. This year’s Nobel laureates have dedicated their careers to deepening our understanding of how cells sense and respond to hypoxic conditions. When oxygen availability is low, the organism enters a state called hypoxia. However, oxygen supply can vary significantly, be it due to physical activity, breath holding during diving, or due to disease. All human cells require a constant supply of O2 to carry out something called oxidative phosphorylation, which is a fancy way of saying that the mitochondria -the cell engines- generate ATP, a messenger substance required for thousands of biochemical reactions within each cell. Here I will attempt to put in lay terms what the three Nobel laureates discovered about the unbelievably complex cascade of molecular events that allow cells to detect and respond to different levels of oxygen, and what this might mean for WHM practitioners.įirst, let’s look at what Kaelin, Ratcliffe, and Semanza have discovered over the past thirty years.Įvery child learns that oxygen is absolutely necessary in order to create energy out of nutrients. Science isn’t always intelligible for non-scientists. We’re doing this by giving the body more O2 during deep breathing, while cutting the supply during breath retentions.
When you learned the WHM breathing techniques -either in a workshop or the video course- you know that we are playing around with varying levels of oxygen (O2). Reading this news, many practitioners of the Wim Hof Method probably wonder how these discoveries relate to the breathing techniques we use. Semenza - recently received the Nobel Prize in physiology and medicine "for their discoveries of how cells sense and adapt to oxygen availability." Three independent physician-scientists from the United States and Britain - William G.
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