The primitive atmosphere where aerobic life started on earth was hypoxic and hypercapnic. Remarkably, an adaptation strategy whereby O2 partial pressure, PO2, in the arterial blood is maintained within a low and narrow range of 1-3 kPa, largely independent of inspired PO2, has also been reported in modern water-breathers. In mammalian tissues, including brain, the most frequently measured PO2 is also in the same low range. Based on the postulate that basic cellular machinery has been established since the early stages of evolution, we propose that this similarity in oxygenation status is the consequence of an early adaptation strategy which, subsequently, throughout the course of evolution, maintained cellular oxygenation in the same low and primitive range independent of environmental changes. Specialized enzymes aimed at protecting cells against O2 toxicity are thought to have appeared very early in evolution but we suggest that preventing high PO2's is also the simplest and most efficient tool for limiting reactive oxygen species (ROS) production. It could be a cue mechanism to widen our understanding of the ageing process.