Genes and lifestyle:
Are we victims of our own success?

Source: Harvard Men's Health Watch

Publication Date: 12/01/2006

"What a piece of work is a man."

As usual, Shakespeare got it right. At their best, humans appear to have a limitless ability to imagine and create, to innovate and build, to aspire and achieve. As man's dreams in the 20th century became realities, he established a way of life that is beyond the wildest imagination of his grandparents. Yet for all its advantages, life in the information age presents potential perils as well as unparalleled opportunities. Unfortunately, some of those perils contribute to diseases that were rare a few generations ago but approach epidemic proportions today.

A scientist speculates

Writing in the August 2004 American Journal of Medicine, Dr. George P. Chrousos of the National Institutes of Health explains the potential hazards of a mismatch between human genetics and human behavior. At the core is the body's stress response. It involves the brain, especially the hypothalamus, the pituitary (or "master") gland, the sympathetic nervous system, and the adrenal glands. In response to stress, this intricate network pours out several hormones such as cortisol and other glucocorticoids, adrenaline and other sympathomimetic amines, vasopressin, and interleukin 6 and other cytokines that mediate inflammation and immunity.

You don't have to be a scientist to know how the stress reaction feels and looks. Your heart beats faster and harder, and your blood pressure soars. Your breathing gets faster and deeper, and your pupils widen. Your muscles tense up, and your hair may bristle a bit. Your skin becomes cool and clammy, your mouth gets dry, and your stomach may churn with tension. You feel alert and awake but tense and nervous.

The changes that go on inside your body are just as impressive. Stress activates your clotting mechanisms and turns up the immune system. Blood sugar levels rise, white blood cells pour into circulation, and urine production slows.

These changes prepare humans to cope with danger. But they evolved when the dangers were predators, privation, and physical dangers. Today, most Americans live in a protected world of plenty. Our world has changed, but the stress response has not.

In his essay, Dr. Chrousos reviews how the mismatch between our genes and our lifestyle may contribute to some important contemporary diseases; a modified version of his table is below.

Genes for survival, genes for disease

Threats to survival Genetically determined survival responses Contemporary diseases that may result
Starvation Energy conservation Obesity and diabetes
Dehydration Retention of salt and fluids High blood pressure
Infection Potent immune system Autoimmune and allergic diseases; septic shock syndrome
Adversaries Arousal and fear Anxiety and insomnia
Dangerous situations Withdrawal from danger, escape Depression and social isolation
Tissue strain and injury Preservation of tissue integrity Pain and fatigue syndrome
Bleeding Promotion of clotting Heart attack and stroke
Source: American Journal of Medicine 2004; 117:205.

As an endocrinologist and geneticist, Dr. Chrousos calls for more research into the survival genes that were once adaptive but are now harmful. He hopes this knowledge will lead to preventive measures and identify targets for drug development. It's a hope we all share -- but we don't have to wait for breakthroughs in genetic engineering to correct this imbalance between our genes and our lifestyle. We should adapt to the dietary patterns and exercise habits that will keep our genes happy and our lives healthy and enjoyable.

On the run

Think about it. Our earliest ancestors depended on their physical prowess for survival. Life itself hinged on obtaining food by hunting and gathering, both strenuous activities. Finding shelter, evading predators, and coping with the whims of Mother Nature also required strength and endurance along with a quick wit.

Anthropologists tell us that at the dawn of humankind, in the late Paleolithic era, people lived in small bands that roamed over large areas to find food and shelter. Human population was sparse; scant resources, low fertility, and a hostile environment limited population to a density of just one person per square mile. Society was simple, with most of the people performing identical tasks. The most important task was obtaining food. Typically, it was a question of feast or famine. One to two days of virtually continuous physical activity were required to obtain sustenance. These bursts of exercise were followed by several days of feasting and celebration -- but even during these primitive holidays, our ancestors were amazingly active, dancing, playing, and traveling up to 20 miles on foot in a single day to visit and trade with other clans. All in all, an average day's physical activity burned up about twice as many calories as a typical American uses today.

The "all-natural" diet

Stone Age people hunted wild game, trapped fish, and gathered fruit, nuts, seeds, and tubers. They weren't able to store food, so they ate what they could when they could. The result was feast or famine; even today, the human metabolism remains dedicated to storing calories in body fat to provide fuel in time of need.

The Stone Age diet was high in protein but very low in fat. Meat was a major source of protein, but wild game was lean and low in fat because the animals ran free and eked out a subsistence living on vegetation -- no pens, grain bags, antibiotics, or hormones for them! Dairy products were unknown, and carbohydrate consumption varied, but the primitive diet was very high in fiber and had plenty of vitamins, iron, and minerals -- except for salt, which was scarce. Caloric consumption was up and down, probably averaging about 3,000 calories a day.

Cultivating change

Change came slowly in the Stone Age. Hunting and gathering remained the dominant way of life for about 30,000 years. But about 10,000 years ago, humans learned how to cultivate crops and domesticate animals, making life easier and more predictable. The population density increased, creating the need for specialized occupations and creating social hierarchies, so people became a source of stress. For most folks, farming and herding required nearly as much physical work as hunting and gathering, but farming produced a new way of eating.

Grains, cereals, and tubers became the main vegetable foods, and wild game was replaced by dairy products and meat from farm animals. As man became dependent on a few crops, dietary diversity suffered and nutritional deficiency diseases arose. Periodic crop failures produced epidemics of malnutrition and starvation. Stored food often spoiled, and microbes passed freely from animals to humans and from person to person in the new villages and towns. New diseases replaced old problems, keeping the average Agricultural era lifespan at about 30 years, a minimal improvement over the hunter-gatherer's life.

The industrial revolution

The agricultural way of life still prevails in much of the developing world, but in the 19th century, the industrial revolution produced incredible changes in the United States and Europe. Labor-saving devices made life much easier, replacing physical labor with mental work. New agricultural methods made food cheap and plentiful. Technology and mass production made refined grains, sugar, and salt -- to say nothing of tobacco and alcohol -- readily available. Our brave new world was born.

The information age

Modern science has accelerated the pace of change and has spread technological advances to the far corners of the globe. Life is much better (and much longer) today then ever before, but some good things have been lost. Exercise is one, dietary diversity another. We've replaced hoes with tractors, brooms with vacuums, and stairs with elevators. Fresh foods are out, refined, processed foods in; that means less fiber and vitamins but more salt, sugar, fat, and calories. Freed from physical labor, people have used their heads to carry science and technology to new heights, creating a society of unprecedented affluence and convenience. But progress has its price. Mental stress is one example, environmental pollution another.

Sedentary living and processed foods extract a price both in health and in dollars. Our genes retain most of the Stone Age imperatives, but life in the fast lane does not. Human DNA cannot provide a substitute for the exercise that has all but vanished from contemporary work stations. The human metabolism is still programmed to cope with the Stone Age threat of starvation, not the burden of overabundance. Evolution is too slow to have yet produced ways to manage today's high-calorie, high-salt, high-fat, low-fiber diet. The body has no new enzymes to fight the effects of tobacco, excess alcohol, and illicit drugs. The nervous system remembers how to respond to the threat of a saber-toothed tiger but has not figured out how to cope with a raging boss or rush-hour traffic. And as industrial pollution changes the environment, a sea of toxins presents new challenges to human genes and human health.

Good genes, bad genes, old genes, new genes

Most of us are lucky enough to have a perfectly healthy set of genes. But some of us have inherited abnormal genes that cause disease. In some cases, just one or two abnormal genes among the human complement of some 30,000 genes can wreak havoc; cystic fibrosis and sickle cell anemia are examples. And in the final analysis, all cancers arise from flaws in the genes that regulate cell growth.

Gene therapy is an experimental attempt to treat disease by introducing healthy genes into patients' cells. It's a tricky business. "Naked" DNA, the genetic material, is not suitable, so scientists attach the DNA to a delivery device, or vector. In one approach, the DNA is attached to a chemical vector, such as a form of fat called a liposome. In the other, more promising, technique, the DNA is injected into a virus, which is then allowed to infect the patient's cells, carrying the new gene along with it.

Does it work? Not yet. Hundreds of gene therapy trials have been performed during the past 15 years, including several dozen attempts to treat prostate cancer. Some partial successes have been reported -- but so have some major side effects.

Scientists at the forefront of gene therapy research remain optimistic. Still, clinical applications are a long way off. For now, we'll have to settle for the genes we have -- and that means adopting the lifestyle suited to our healthy genes. It's a shame to squander good genes with bad habits.

Back to the future

Molecular medicine is on the verge of making genetic engineering a clinical reality, but it can't possibly bring Stone Age genes up to Space Age standards. Since science can't reshuffle your genes, the only way for you to restore nature's balance is to adopt a more natural lifestyle.

Fortunately, you can get back to basics without returning to the farm, much less the savannah. Here's how:

Eat well. Consume a variety of foods to restore nutritional diversity. Favor vegetable-based foods that provide essential vitamins and minerals. Eat whole-grain products that contain the fiber you need. Avoid animal fat; get your protein from fish, poultry, beans, and legumes. Reduce your dependence on processed foods, salt, and simple sugars. Eat smaller meals on a regular schedule, balancing your caloric intake with your expenditure of energy.

Exercise regularly. Add physical activity to your daily life by climbing stairs, walking instead of driving when possible, and carrying your own parcels. Set aside 30-45 minutes nearly every day for moderate exercise; walking, jogging, biking, swimming, dancing, gardening, and tennis are good examples. For best results, add exercises for balance, stretching exercises, and prudent resistance training.

Control stress. Balance work and play, stimulation and relaxation, companionship and solitude. Achieve all you can, but take time to enjoy every day.

You don't need a spear or loincloth to get back to basics. You can incorporate the best aspects of modern life to live naturally, enjoyably, and healthfully. It's all in your genes.

Copyright © 2006 by President and Fellows of Harvard College.