It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.

Charles Darwin

Stress is now the greatest threat to our health. About half of American adults have one or more preventable, stress-related chronic diseases. Cardiovascular disease, type 2 diabetes, certain cancers and obesity are all triggered by stress.

But not in the way you would think. We suffer from too little stress.

That’s absurd, you say. Why would an absence of stress make us sick?

It is our design.

Our genome is the product of millions of years of adaptation to a lifestyle that provided a daily dose of stressors. A day in Paleolithic life (99.5% of Homo sapien existence) entailed an unpredictable food supply, the consumption of a broad spectrum of wild plants, hunting, gathering, and exposure to the elements.

Most people’s response to the loss of that life is, “Thank God”. However it is precisely this loss of wild foods, intermittent fasting, formidable daily physical activity often under fasting conditions and exposure to temperature fluctuations and sunlight that is making us sick.

These stressors have been shown to activate adaptive cellular responses that protect against chronic disorders such as cardiovascular disease, cancer, diabetes, Alzheimer’s and Parkinson’s diseases. This adaptive response to moderate, intermittent stress is known as hormesis. I will call it stressing- in.

When stressing-in, stability is achieved through change.

We can exist only within a narrowly defined internal environment. For instance, we may be able to live indefinitely in conditions that range between about 4 and 35 degrees C (40 and 95 degrees F). However if our core body temperature drops or increases by 5 degrees C, death is likely. The maintenance of body temperature, blood oxygen levels, fluid and electrolyte balance, and metabolic rate are examples of homeostasis at work.

While such stability is necessary for survival, it is not enough for health. Our body has a love-hate relationship with change. It conservatively guards a status quo but thrives on challenges to this balanced baseline. Another term for such essential challenges is stress. Without the changes triggered by specific stressors the healthy stable state is lost.

Study of the formative stressors in our evolution has provided a blue print for promoting health now.

How to Stress-In

Caloric Restriction and Fasting

The most successful method for extending an animal’s lifespan and healthspan is caloric restriction. By significantly decreasing food intake, lifespan lengthens. This stressor triggers a cellular stress response that renders the animal more resistant to chronic diseases and slows aging. One of the ways this works is through a dramatic decrease in inflammation. Inflammation characterizes the early stages of most chronic diseases and is the key driver of the aging process.

Intermittent fasting can take many forms (e.g. skipping breakfast and prolonging the overnight fast) and has been shown to provide many of the benefits of longer (e.g. 24 hour) fasts or a daily low calorie diet. Such fasting recapitulates the unpredictable food supply that stressed our ancestors.

One must also question the prioritization of breakfast in a sedentary culture. Our development in a light-dark cycle gave rise to a circadian rhythm that directs a corresponding active (light)-inactive (dark) cycle. The morning cortisol awakening responsefrees energy stores to fuel the requisite foraging activity that began each day. We forget that before agriculture (99.5% of our existence), this was always the sequence. Physical exertion necessarily preceded feeding. A surge of cortisol at sunrise has generated energy for millions of years without breakfast.

Physical Activity

While exercise causes some low-grade oxidation and inflammation in the short term, it provides powerful anti-inflammatory effects in the long term. Researchers studied the effect of exercise with and without the antioxidants vitamins E and C. When exercise was preceded by these vitamins the beneficial effects were eliminated. In other words, blocking the mild stress of the exercise voided many of its therapeutic effects.

The 10,000 steps per day goal is a good place to start.

Attempt to integrate movement into every part of the day. Even the best exercise routine does not undo the negative effects of prolonged sitting. Set an alarm for 20 minute intervals and stand up for at least one minute. Take all your phone calls standing up. When watching television, stand up for every advertisement. If you commute by bus/subway/train, try standing up for the ride.

Because the activity pattern of hunter-gatherers is long periods of slow pace interspersed with intense exertion, interval training with a similar pattern best mimics this stressor. And don’t take your vitamins before exercising.


This is good news for those looking for exercise substitutes. Exercise mimetics is the odd but essential field focused on how to mimic the physiological effects of physical activity without the physical activity. You might say, an armchair science. Odd, because it involves highly sophisticated and costly research attempting to uncover what happens when you break a sweat, something neither sophisticated nor costly. Essential, because inactivity is now a leading cause of illness.

A hot bath or sauna warms our muscles, as does exercise. This increase in temperature triggers what’s called the heat shock response, a cellular stress response. Heat shock proteins share pathways associated with the body’s reaction to exercise. They have been shown to improve insulin sensitivity (something that is lost in diabetes, obesity and metabolic syndrome), reduce inflammation, decrease body fat, improve endurance, decrease muscle atrophy, stimulate neurogenesis (growth of new brain cells) and prolong healthspan.


Although less comfortable for most, cold exposure provides one of the most powerful positive stressors.

Cold triggers the release of norepinephrine, a hormone involved in vasoconstriction (narrowing of the arteries to prevent loss of heat in the periphery) and a neurotransmitter effecting concentration and mood.

Low norepinephrine levels are associated with impaired concentration, low energy and depressed mood. Conversely, cold-induced increases in norepinephrine levels can improve concentration, raise mood and elevate energy levels. Norepinephrine also serves as a potent anti-inflammatory agent.

Cold can generate both heat shock proteins and its own unique cold shock proteins. These compounds have demonstrated positive effects on the immune system, the ability to lower pain levels and increase the body’s production of protective antioxidants.

What makes many endure cold exposure is the promise of weight loss. The body responds to cold by increasing metabolism in order to produce heat. This occurs primarily in fat tissue. The cold-induced rise in norepinephrine triggers the release of an uncoupling protein in mitochondria, the energy factories of every cell. The effect of uncoupling proteins can be compared to revving the engine of a car that has been put into neutral. No energy is harnessed but lots of heat is given off. Uncoupling proteins also increase metabolism by producing more mitochondria in fat tissue, a process known as the browning effect (browning because mitochondria appear brown under the microscope). This conversion of typical white adipose (fat) tissue into the more active brown adipose tissue (BAT) revs up metabolism and burns more fat.

Plant Food

In a way, plants are black belts in the hormesis department. Because they can’t move away from environmental stressors, they have developed a magnificent arsenal of adaptive responses to such stressors as UV radiation (sunlight), fluctuations in hydration, soil nutrients, temperature and a variety of infections. And they have had about 1 billion years to hone these responses. That dwarfs our time on the planet. It’s no coincidence that one-thirdof the top 20 drugs on the market are plant-derived.

In eating plant foods, we benefit from the compounds they make in response to their stressors, called phytochemicals. Noxious properties of these agents protect plants from being eaten. However at the subtoxic doses ingested by humans, the phytochemicals induce adaptive stress responses.

Unfortunately, we consume very few plant foods in comparison to our hunter-gatherer days. In addition, the plant foods we do eat are not wild. We have done to our food what we have done to ourselves. In cultivating our crops, we create optimal conditions for their growth and survival. This has decreased their stress and therefore the good stuff that they can pass on to the consumer.


As opposed to stressing-in, this is the stress we are not made for. It is the persistent exposure to psychological stress. The fight-flight response is the only stress response our biology knows. It is designed primarily for external threats such as predators and hostile peers. These situations required energy for a burst of physical activity and usually were resolved, for better or worse, in minutes or hours.

The ongoing nature of modern stress results in chronic low- grade fight-flight activation that dumps fuel in the form of glucose and fatty acids into our bloodstream and revs up heart rate and blood pressure. A physical response is the only way to turn off this up-regulated biology and return to baseline. This rarely occurs.

Chronic stressing-out in the context of excess calories, controlled temperatures and a sedentary lifestyle now causes our biggest health problems: obesity, hypertension, cardiovascular disease and a diminishing health span.

The ironic task of contemporary society is to recreate those ancestral stressors we so successfully eliminated. This alone will allow our exquisitely adaptive biology to return to its evolutionary preferred setting. This is home. This is health.

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