Hypoxia: life on the edge

Hypoxia and its corollaries pose both negative and positive pressures to multicellular eukaryotes. Evolutionarily, life developed under hypoxia, and the building blocks were established under conditions close to anaerobiosis; therefore, reason exists to expect that certain biologic processes may perform preferentially under hypoxia. Evolving evidence suggests that by providing an environment of reduced oxidative stress, hypoxia may help preserve the biologic functions of some cells and prevent senescence. Hypoxia provides essential signals for development, trimming redundant tissue by inducing apoptosis and driving the growth and development of oxygen and nutrient delivery systems, as well as those for waste management. The pathologic consequences of hypoxia and ischemia, including acidosis and oxidative stress associated with hypoxia-reoxygenation, form the basis of most of the major diseases confronting humans, including heart disease, cancer, and age-related degenerative conditions. The 11 articles in the forum touch on multiple aspects of hypoxia, in particular, signaling responses, adaptations, and diseases that result from imbalance and fluctuations of supply and demand. Although we have developed elaborate processes to combat hypoxia and oxidative damage, it is clear that oxygen and our environment still control us, perhaps even more than they did our unicellular ancestors 2 billion years ago.