Mitochondrial allostatic load

Mitochondrial allostatic load puts the ‘gluc’ back in glucocorticoids
Nature Reviews Endocrinology  10, 303–310 (2014)
Martin Picard, et al.

The link between chronic psychosocial [stress] and metabolic stress and the pathogenesis of disease has been extensively documented.
Nevertheless, the cellular mechanisms by which stressful life experiences and their associated primary neuroendocrine mediators cause biological damage and increase disease risk remain poorly understood.

The allostatic load model of chronic stress focuses on glucocorticoid dysregulation.
In this Perspectives, we expand upon the metabolic aspects of this model—particularly glucose imbalance—and propose that mitochondrial dysfunction constitutes an early, modifiable target of chronic stress and stress-related health behaviours.
Central to this process is mitochondrial regulation of energy metabolism and cellular signalling.
Chronically elevated glucose levels damage both mitochondria and mitochondrial DNA, generating toxic products that can promote systemic inflammation, alter gene expression and hasten cell ageing.
Consequently, the concept of ‘mitochondrial allostatic load’ defines the deleterious structural and functional changes that mitochondria undergo in response to elevated glucose levels and stress-related pathophysiology.

How Our Stone Age Bodies Struggle To Stay Healthy In Modern Times

How Our Stone Age Bodies Struggle To Stay Healthy In Modern Times
September 30, 2013

a partial list of mismatch diseases:

  • acid reflux
  • acne
  • anxiety
  • depression
  • asthma
  • certain cancers
  • type II diabetes
  • flat feet
  • hypertension
  • Irritable bowel syndrome
  • low back pain
  • osteoporosis

If you got sick, you probably wouldn’t go to an evolutionary biologist to get treated.
But Daniel Lieberman, professor of evolutionary biology at Harvard University, says that his field can help you understand why you got sick, and make you more aware of healthy and harmful behaviors.

In his new book, The Story of the Human Body: Evolution, Health and Disease, Lieberman traces these troubles back to their origins.

On “mismatch diseases”
Many of the illnesses that we confront today are what evolutionary biologists called “mismatch diseases“:
Diseases that occur because our bodies are poorly or inadequately adapted to environments in which we now live.
An example would be eating large amounts of sugar or being very physically inactive leads to problems like diabetes or heart disease that then make us sick.

On our relatively “new,” unfettered access to sweet foods
Now we have access to abundant quantities of sugar and simple carbohydrates, which we evolved to love because they’re full of energy, but we don’t have the metabolism.
We don’t have the bodies that are able to cope with those kinds of levels of sugar.

We’re actually a very fat species, compared to other primates and most other mammals.
The average primate, a chimpanzee or a monkey, has maybe about 5 or 6 percent body fat, whereas a thin human being, a very – you know, a supermodel has more, much more body fat than that.

type 2 diabetes … there are genes that protect some people more than others from the disease.
These are genes that probably evolved fairly recently that give some populations – it tends to be Europeans – better ability to cope with high-glycemic foods, and that means foods that cause more sugar in your bloodstream.

But some populations, for various reasons, probably chance, never evolved as many of those adaptations. So they tend to be more prone to developing diabetes and obesity from the same kinds of diets.
So India and China are examples of countries where these epidemics seem to be growing faster because of a lack of selection that somehow occurred, or just the genetic variation that made it possible for evolution to give some protection.

natural selection

On why stress leads us to crave comfort foods
cortisol … makes you more alert. But it also exacts a toll.
Cortisol makes us want to bring in more energy to cope again, with those energetic needs. So stress activates basic primal urges to eat calorie-rich food

On the way the stress we experience today is different from Paleolithic stress
Stress creates this vicious cycle, this positive feedback loop.
When you’re stressed you crave unhealthy foods, but when you’re stressed you also have a harder time sleeping, and when you have a harder time sleeping that elevates your levels of stress.
It just sets off this chain reaction that keeps going on and on.
… much of the stress we create today results from social conditions … our jobs, our commutes, not having enough money … And when stress becomes chronic, then it helps feed a variety of mismatch diseases that make us ill, that make us depressed, that make us anxious, that make us overweight, which causes more stress and then keeps the cycle going.