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Source: Journal of Applied Physiology, July 2002.

The need for physical activity is hot wired into the body’s expectations; When that activity does not occur, nutritional “thrifty genes” react, causing a steep rise in common chronic conditions

BETHESDA, MD – (July 10, 2002) – The results of the most extensive research investigation into the relationship between chronic health conditions and physical inactivity have been released by a team of “obesity sleuths.”

They conclude that today’s skyrocketing levels of chronic diseases are due to the collision between the body’s total gene complement of a set of chromosomes, — programmed 10,000 years ago to anticipate physical exertion, and the inactivity endemic to 21st century sedentary societies.

Nutritional “thrifty genes” may further exacerbate the deterioration of the human body, which takes the form of common, chronic disorders, once thought to be rare.

The Study

The study entitled “Waging War on Physical Inactivity: Using Modern Molecular Ammunition Against an Ancient Enemy,” is the latest report from the obesity research team of Frank W. Booth and Espen E. Spangenburg, both of the Departments of Biomedical Sciences and Physiology and the Dalton Cardiovascular Institute at the University of Missouri, Columbia, MO; Manu V. Chakravarthy, of the Department of Internal Medicine, University of Pennsylvania, Philadelphia, PA; and Scott E. Gordon, of the Departments of Exercise and Sports Sciences and of Physiology and the Human Performance Laboratory, East Carolina University, Greenville, NC. Their study appears in the current edition of the Journal of Applied Physiology, a publication of the American Physiological Society.

The team set out to identify the underlying genetic and cellular/biochemical bases of why a sedentary lifestyle produces chronic health disorders. They support the hypothesis that humans have inherited a genome programmed for physical activity by selective forces from the Late Paleolithic era (10,000 years ago), when physical activity was necessary for survival.

Another associated hypothesis that was examined in this research effort is that a lack of physical activity leads to failure of the maintenance of normal signaling by cellular networks that activate that genome.

Since the normal orchestration of protein expression in cells in humans was selected during evolution, when physical activity was higher than today, an altered protein expression of cells from sedentary individuals is associated with a higher incidence of chronic conditions.

As part of their efforts, new conclusions have been reached on how physical inactivity affects at least 20 of the most chronic and deadly medical disorders. They suggest that all these conditions share common genetic inheritances that were supported by physical activity. When physical activity diminished, chronic health conditions occurred.

Needs for the Paleolithic Age

Daily physical activity was an integral, obligatory aspect of our ancestor’s existence. The weekly activity pattern of hunter-gatherers of the Paleolithic Stone Age period (c. 8,000 B.C.) required several days of fairly intensive physical activity followed by days of rest and light activity.

Men commonly hunted from one to four consecutive days each week while women gathered every two to three days. The physical labors involved in tool making, butchering, food preparation, carrying firewood and water, and moving to new campsites were supplemented by dances, often lasting hours, as a major recreational activity in many cultures.

(Lack of) Needs for 21st Century Americans

Twenty-first century Americans still possess late Paleolithic, pre-agricultural hunter-gatherer genes, and, perhaps nutritional “thrifty genes.”

Since our food abundant society makes physical activity no longer obligatory for survival, the sedentary lifestyle has emerged, disrupting the normal homeostatic mechanisms that have been programmed for the proper metabolic fluctuations necessary to maintain health. Physical inactivity interferes with the genome thus becoming an initiating factor in the molecular mechanisms of disease.

This assessment of chronic disorders addressed a wide range of maladies that affect a considerable number of Americans. Disorders were considered and conclusions were reached.

Highlights include:


• Breast Cancer: Sedentary females, compared with physically active women, are less likely to have primary and secondary anenorrhea, delayed menarche, and irregular cycles, all associated with a reduced development of breast cancer.

• Colon Cancer: Physical inactivity was the risk factor most consistently shown to be associated with the increased risk of colon cancer. A 50 percent reduction in the incidence of this disease was found in those with the highest level of physical activity.

• Pancreatic Cancer: Walking or hiking less than 20 minutes a week was associated with twice the risk of pancreatic cancer when compared with those who performed the exercise for more than four hours a week.

• Melanoma Cancer: Sedentary men and women had a 56 and 72 percent, respectively, higher incidence of melanoma than those exercising five to seven days a week.

Cardiovascular Diseases

• Heart disease, coronary artery disease, angina, and myocardial infarction: Undertaking a moderate-intensity physical activity would prevent 250,000 deaths each year, 12 percent attributed to these medical conditions.

• Heart disease: congestive heart failure: Exercise may improve the condition of people afflicted with this disorder; physical inactivity may be a determinate factor to their time of death.

• Hypertension: Tests found that inactivity led to blood pressures in sedentary individuals being substantially higher than in those who were active.

• Stroke: Physical activity lowers blood pressure, facilitates weight loss, and decreases the chance for Type 2 diabetes, a major cause of strokes.

Metabolic Diseases

• Type 2 diabetes: Most of the prevalence of Type 2 diabetes in the United States can be attributed to a change in lifestyle that involves a genome evolved from a Paleolithic lifestyle. Cultures that still have hunter-gatherers have low incidence of this disease.

• Obesity: Sedentary individuals can lower their risk of many disorders by increasing their physical activity, regardless of whether they are normal or overweight.

Musculoskeletal Disorders

• Osteoarthritis: Appropriate exercise, both therapeutic and recreational, is an effective therapy in the successful management of this disorder. The benefits are flexibility, muscular conditioning, and cardiovascular and general health.

• Rheumatoid Arthritis: Exercise for patients with this disorder minimizes loss in muscle strength but not in bone loss.


This effort clearly points out that a sedentary lifestyle leads to a breakdown in the body’s biomedical system and a failure of genes leading to chronic disease.

Now, the American public has a baseline of information of how to develop an optimum design for living that will contribute to a healthy lifestyle and to the avoidance of disorders caused by inactivity.

This research also suggests that the publicized searches for genes causing chronic illnesses are too limited. In addition, scientists should explore how selected “activity” genes are misexpressed as a result of a sedentary lifestyle.

These findings challenge those engaged in using the human genome sequence to fight disease to recognize the “activity genes” that produce diseases when inactivity occurs. They repeat their call for Americans to participate in more physical activity to prevent the advent of a wide range of chronic disorders.

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

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Updated: October 30, 2012 — 7:02 pm

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