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Physical exercise has systemic effects, and it can regulate all the organs. The relative maximal aerobic oxygen uptake (VO_2max) could have been important in the evolution of humans, since higher VO_2max meant better hunting abilities for the Stone Age man. However, it appears that high level of VO_2max is also important today, in the 21th century to prevent cardiovascular diseases, cancer and neurodegenerative diseases. High level of VO_2max is not just preventive against a wide spectrum of diseases, but it associated with better function of many organs. Relevant data suggest that high level of VO_2max is a key factor in prevention of diseases and survival even at the modern civilized world.