Evolution, physical activity, and human health

The chronic diseases we see today are often the result of poor lifestyle choices.  Cardiovascular disease, Type 2 diabetes, obesity, cancer, arthritis, depression, and Alzheimer's disease are all considered normal parts of the aging process and are often called diseases of aging.  The problem is, when you look at "less civilized" cultures, particularly modern day hunter gatherers, these diseases either don't exist or are insignificant even in older members.  This has caused many to postulate that the Western lifestyle may be a significant factor in the prevalence of these diseases.

In 2002, Booth wrote a paper going over exercise and gene expression(1).  This paper is a classic in the evolutionary medicine arena because it shined a light on the effect of exercise on gene expression and proposed the theory that genes expressed as a result of physical activity would promote disease in a person who doesn't meet the necessary threshold to activate these genes.  In other words, the lifestyle diseases that are often attributed to aging may be, at least partially, from a deficiency in physical activity.

 

Booth's primary focus was on the notion that physical activity increased muscle mass and fuel utilization, improved cardiovascular function, and improved cellular insulin sensitivity while physical inactivity did the opposite.  Given that lower muscle mass, poor cardiovascular function, and poor insulin sensitivity are either seen in or associated with most of the lifestyle diseases seen in Western culture, it is fair to say that all of these factors may play a role in the relationship between Western disease and physical inactivity.  However, current research adds more to the story.

A review from 2010 discussed the relationship between inactivity and an overly sensitive stress response(2).  Recently, the author of that study was able to identify the physiological change in the brain that come with high levels of physical inactivity.  He found that physical inactivity causes a re-wiring in the rat brain.  Specifically, it causes a more dispersive branching of neurons in the rostral ventrolateral medulla(RVLM), an area of the brain that helps control the stress response(3).  The researchers believe this increased branching is what causes the neurons in the RVLM to be more responsive to stress in physically inactive rats.  While this study has not been repeated in humans, it bears to note that increased sensitivity of the stress response, also called increased sympathetic tone, is also found in many of the lifestyle diseases mentioned above and sedentary behavior is also strongly associated with these diseases(4, 5, 6, 7) and the low grade inflammation that accompanies them(8, 9).

There are other avenues within inactivity physiology that apply to health and are worth mentioning.  During aerobic metabolism, reactive oxygen species(ROS), or free radicals, are continuously generated(10).  Free radicals are molecules with an unpaired electron that serve vital roles in cellular function, but react with healthy molecules within the body and cause oxidative stress when not held in check.  Oxidative stress occurs when free radical generation outpaces the ability of the body's antioxidant defense systems to deal with free radicals.  The body's antioxidant pathways donate electrons to free radicals and help keep free radicals at a healthy level.  As I mentioned in this previous blog, prolonged sitting causes changes in genetic expression that reduce antioxidant and anti-inflammatory pathways and reduce insulin sensitivity.  This would increase oxidative stress which is another physiological factor associated with lifestyle diseases.  In addition, increased oxidative stress leads to higher levels of inflammation which are also associated with these diseases.

Some people attempt to head off oxidative stress by taking antioxidants supplements.  The problem with this is that when supplemental antioxidants are taken and they meet up with a free radical, they donate an electron to the free radical which makes the former antioxidant a free radical, albeit a weaker one.  The antioxidants generated by the body's antioxidant defense system, particularly glutathione, are able to donate electrons to free radicals as well as recharge antioxidants that become free radicals as a result of donating an electron.  This makes the body's antioxidant defense system far more powerful than any antioxidant you can take orally.

What makes this avenue of inactivity physiology particularly interesting is that recent evidence has shown that the average daily energy expenditure of Hadza hunter gatherers is the same as Westerners when controlled for body size despite the physical activity level of the Hadza being greater(11).  Since a person at rest is primarily utilizing aerobic metabolism, it is safe to assume that both groups are either generating the same number of free radicals or the Westerners are generating more based on their larger size alone.  On top of this, the increased level of sedentary behavior associated with the Western lifestyle could potentially induce higher levels of oxidative stress through a reduction in antioxidant gene expression while the physically active lifestyle of the Hadza may promote health by keeping free radical levels at an appropriate level.  Since the Western lifestyle diseases discussed earlier are also associated with high levels of oxidative stress and hunter gatherers like the Hadza rarely experience them, it makes you wonder if shutting down these pathways contributes to the Western lifestyle diseases.  In other words, a deficiency in physical activity may in fact be a strong contributor to the lifestyle diseases that are prevalent in Western cultures for many physiological reasons.