Run for Your Life Humans Evolved to Run

COMMENT ILLUSTRATION BY PHIL DISLEY BY ILLUSTRATION

Run for your life Humans evolved to run. This helps to explain our athletic capacity and our susceptibility to modern diseases, argue Timothy Noakes and Michael Spedding.

he forthcoming Olympics in London Charlie, holds the English marathon record regularly to chase down meat. For many, will celebrate the performance capac- and won Olympic bronze in 1984 by ignor- exercise is no longer an integral part of daily ity of humans and our remarkable ing drink stations at crucial stages in the Los life, leading to a host of modern ailments. Tability to prepare our bodies and minds for Angeles marathon. We began exchanging In short, we think specific tasks. But, at the same time as we e-mails. Eventually, that correspondence “Most humans that exercise is not just are pushing our bodies to new limits in ath- coalesced into the theory we outline here. today do not important for general leticism, we are experiencing unprecedented Over millions of years, humans evolved live in an health — it is essen- levels of relatively modern diseases such as from tree-dwelling apes to become Homo environment tial to the molecular obesity, diabetes and psychiatric and neuro- sapiens, capable of elite athleticism1. Simply where they memory of who we degenerative disorders. put, we evolved to run. While early homi- must chase are. Without it, we are We, the authors, were both considering nins were undergoing intense skeletal and down meat.” at risk of being obese the modern paradox of elite athleticism and metabolic changes, major changes also and diabetic, and of growing susceptibility to disease when we occurred in their brains2. We propose that developing diseases linked to brain function, met at a sports conference in Glasgow, UK, these changes have rendered us dependent such as psychiatric disorders, dementia and in 2010. Noakes is a sports scientist who has on mental and physical exercise to maintain even violent behaviour. run more than 70 marathons and ultramara- brain health. Exercise doesn’t just help mus- thons. He was presenting data suggesting that cles — it activates our brains, particularly COOL AND SWEATY humans’ unmatched ability to dissipate heat through one pathway that helps to increase The ancestors of modern humans were when running, even when drinking spar- the number of neuronal connections. omnivorous apes with bodies that were ingly, might have been a key element that Most humans today do not live in an more suited to living in trees than hunting enabled them to evolve from tree-living pri- environment where they must exercise in open habitats. Over the past few million mates. Spedding, a pharmacologist present- years, the climate underwent dramatic shifts ing studies of how stress can increase the risk LET THE GAMES BEGIN and Africa changed from a largely forested of psychiatric disorders, has run more than Science and the Olympics ecosystem to a more open savannah. Our 100,000 kilometres and been a competitive nature.com/olympics20 2 ancestors, caught at the edge of the retreat- athlete for more than 40 years. His brother, ing forests, became less adapted for climbing

19 JULY 2012 | VOL 487 | NATURE | 295 © 2012 Macmillan Publishers Limited. All rights reserved COMMENT trees. By 2 million years ago, they had evolved the developing brain (see ‘Memory jog’). hypothalamus, controlling body weight a skeleton that could support walking and Although some research has yielded and energy homeostasis7. It also triggers the running — partly so that they could hunt mixed results about the benefits of exercise brain mitochondria — the powerhouses of by pursuing individual animals for hours at for the brain5, the literature in general shows the cell — to use oxygen more efficiently8, a time1. that regular exercise can have many cogni- in a similar way to how exercise helps to For more than 1 million years, there were tive benefits. Some research suggests that increase overall VO2max in humans. no weapons other than stones or sharpened exercise has antidepressant effects, at least As humans needed more brain power sticks. The best weapon was endurance. The against mild depression, and may even offset to track prey, increases in BDNF may have predators had to outlast their prey, and so had Alzheimer’s disease: an exercise programme helped to build up the hippocampus and many adaptations that enabled them to walk has been shown to increase the volume of the prefrontal cortex — key brain areas that are and run long distances, forcing their prey to brain’s hippocampus. More data are needed involved in spatial mapping, decision-making gallop. Because four-legged animals cannot to obtain a clearer picture of the effects of and control of context, fear and emotions, lose heat by panting and galloping at the same exercise on cognition. Ongoing clinical including violence8–10. BDNF has a crucial time, human hunters eventually drive their trials are testing the effects of exercise on role in the prefrontal cortex, a region that is prey into heat stroke, so that the animal can be Alzheimer’s disease and schizophrenia. also strongly associated with psychiatric dis- caught and killed with very simple weapons. orders9. Not surprisingly, BDNF is reduced in The ability of humans to dissipate heat EXERCISE FOR LIFE hippocampal and cortical regions in models comes from our lack of body hair and capac- We believe that at least some of these ben- of stress and psychiatric disorders10, as well as ity to breathe through our mouths and to eficial effects are mediated by BDNF. First, in Alzheimer’s disease. Putting it all together, sweat at rates of up to 3 litres an hour, much circulating BDNF is increased by exercise, we think that exercise increases BDNF in key more effective than panting. In a 3-hour partly by release from the nerve–muscle areas of the brain, which, in turn, has physi- hunt — or in a marathon — fit humans can junction into the blood. In muscle, BDNF ological effects that help to protect humans safely lose up to 10% of their bodyweight3. can increase protein synthesis and fat metab- from psychiatric problems, including violent At the same time, the hunter needed plan- olism5,6, which are key targets of exercise. behaviour. ning and spatial navigation to follow prey Mice that lack BDNF become obese and Not all of the health benefits of exer- for hours, coupled with social interactions there are strong inverse links between BDNF cise stem from the effects of BDNF alone, so that groups could work together to isolate and type 2 diabetes7 — a disease for which it because diabetes and obesity are known to prey4. Primitive hunter-gatherer societies is well known that exercise, with the appro- have other, multiple causes. Importantly, the have a uniquely human social structure with priate dietary changes, is the best therapy modern diet — which is far removed from multiple interactions between non-family allied to medication. the whole foods our ancestors ate — can members, requiring advanced social skills4. In the brain, BDNF increases neuronal itself lead to obesity and inflammation, Within a relatively short time, our ancestors’ connections and is crucial for some aspects which counteract many of exercise’s benefits. skeleton, brain, spatial tracking, communi- of memory6. BDNF plays a part in the A lack of exercise may have multiple, long- cation and ability to dissipate heat shifted term damaging effects, particularly when dramatically, allowing them to fill a very coupled with a poor diet. Simple exercise different niche. They developed longer legs, MEMORY JOG programmes in schools and sports clubs, The bene cial eects of exercise on the body shorter toes, longer Achilles tendons, wider and brain are increasingly thought to be for example, are probably the most cost- shoulders and a stronger gluteus maximus mediated by the brain protein BDNF. effective investments a society can make in for running1. In addition, they evolved larger its psychological and physical health. Exer- weight-bearing joints that could support long cise may be cheap, but the consequences of runs while avoiding too much damage. ignoring it are costly. ■ It is likely that humans also have a much EXERCISE higher metabolic capacity than our ances- Timothy Noakes is professor of exercise tors did, measured by our ability to take up and sports science at the University of Cape and use oxygen (VO2max). We are the only Town, Rondebosch 7701, South Africa. primates with the aerobic capacity to sup- Michael Spedding is a pharmacologist and port long-distance running. It is otherwise lives at Le Vésinet, near Paris, France. restricted to migratory ungulates (horses, e-mails: [email protected]; wildebeest) and social carnivores (hyenas, INCREASE IN [email protected] wolves). Humans evolved from animals BRAIN-DERIVED 1. Bramble, D. M. & Lieberman, D. E. Nature 432, with a low VO2max to the modern endur- NEUROTROPHIC FACTOR 345–352 (2004). ance athlete’s maximum capacity approach- 2. Konopka, G. & Geschwind, D. H. Neuron 68, Ventromedial 231–244 (2010). ing 90 millilitres of oxygen per kilogram of prefrontal cortex 3. Noakes, T. Waterlogged: The Serious Problem body mass per minute. of Overhydration in Endurance Sports (Human Exercise remains central to our basal Kinetics, 2012). metabolism, even though it is no longer a 4. Hill, K. R. et al. Science 331, 1286–1289 (2011). 5. Chalder, M. et al. Br. Med. J. 344, e2758 (2012). core part of life for some human popula- • Improves metabolism. 6. Mattson, M. P. Ageing Res. Rev. 11, 347–352 tions. For example, persistence hunting led • Opposes neurodegenerative processes. (2012). to humans having great capacity to conserve • Acts on spinal cord to reduce heart rate. 7. Noble, E. E., Billington, C. J., Kotz, C. M. & • Reduces rates of obesity and type 2 Wang, C. Am. J. Physiol. Regul. Integr. Comp. sodium and retain water when either are in Physiol. 300, R1053–R1069 (2011). 3 diabetes in mice. 8. Markham, A. et al. Eur. J. Neurosci. 35, 366–374 short supply . • Increases connectivity between neurons. We think that one protein could have (2012). • Triggers brain mitochondria to use oxygen 9. Agid, Y. et al. Nature Rev. Drug Discov. 6, 189–201 been central to these dramatic physiologi- more eciently. (2007). cal changes, both mental and physical: brain- • Has a role in psychiatric and 10. Qi, H. et al. Neuropharmacology 56, 37–46 (2009). neurological disorders. derived neurotrophic factor (BDNF), which M.S. declares competing financial interests; see increases with exercise and play, and sculpts go.nature.com/rhkkl5.