Evolutionary aspects of human exercise--born to run purposefully.

This article is intended to raise awareness of the adaptive value of endurance exercise (particularly running) in the evolutionary history of humans, and the implications of the genetic disposition to exercise for the aging populations of modern technology-driven societies. The genome of Homo sapiens has evolved to support the svelte phenotype of an endurance runner, setting him/her apart from all other primates. The cellular and molecular mechanisms underlying the competitive advantages conferred by exercise capacity in youth can also provide a survival benefit beyond the reproductive period. These mechanisms include up-regulation of genes encoding proteins involved in protecting cells against oxidative stress, disposing of damaged proteins and organelles, and enhancing bioenergetics. Particularly fascinating are the signaling mechanisms by which endurance running changes the structure and functional capabilities of the brain and, conversely, the mechanisms by which the brain integrates metabolic, cardiovascular and behavioral responses to exercise. As an emerging example, I highlight the roles of brain-derived neurotrophic factor (BDNF) as a mediator of the effects of exercise on the brain, and BDNF's critical role in regulating metabolic and cardiovascular responses to endurance running. A better understanding of such 'healthspan-extending' actions of endurance exercise may lead to new approaches for improving quality of life as we advance in the coming decades and centuries.