Living a long, healthy life is more about handling stress and avoiding disease than chronological age, say two leading researchers in the fields of neurobiology and psychoneuroendocrinology.

From a review of studies on how stress hormones affect the brain, TheDoctorWillSeeYouNow's aging expert Bruce McEwen, Ph.D., of The Rockefeller University, finds more evidence that biological and behavioral stress can cause damage when they go on for a long time. "Acute stress seems to enhance immune function and improves memory but chronic stress has the opposite effect and can lead to disorders like depression, diabetes and cognitive impairment in aging," said Dr. McEwen.

People suffering chronic stress, said McEwen, are more likely to have decreased telomerase activity. Telomerases are enzymes that regulate how many times an individual cell can divide. Decreased telomerase activity can cause cells to stop dividing; this is thought to cause or contribute to aging and age-related disease.

There is also new evidence that the brain is more active in directing stress response than previously thought, said McEwen. The brain interprets what is threatening and then regulates the behavioral and physiological responses through the autonomic, immune and neuroendocrine systems. If the brain is under too much stress for too long, said McEwen, "we can see structural and functional remodeling changes that affect how it functions."

"These brain changes, which appear to be reversible, can be changed not only by pharmaceutical agents but also by lifestyle changes like exercise, diet and social support," said McEwen.

Another review of the interactions of the brain, stress and the endocrine system, shows how cumulative stress and disease may define age more than mere chronology. What happens is that certain diseases start to occur when tissue-building anabolic hormone levels start to decrease, and tissue-fueling catabolic hormones start to increase. Catabolic hormones, including cortisol — a "stress hormone" — can become too active and actually break the body down.

An imbalance between anabolic and catabolic hormones may be responsible for many of the psychiatric and medical diseases of old age, said researcher Elissa S. Epel, PhD, of the University of California, San Francisco.

Chronically elevated cortisol, said Epel, reduces lean mass, bone density and shifts fat distributions. These can precede diseases such as osteoporosis, metabolic syndrome, Alzheimer's disease and major depression. On the positive side, lifestyle and exercise changes can modify some of the hormonal effects that accelerate aging.

Healthy centenarians, said Epel, are exposed to more chronic stressors (e.g., health problems, and loss of family and social connections), but do not necessarily experience greater daily stress. The authors believe that the healthy centenarians are using coping techniques such as keeping active and maintaining strong social ties to moderate stress.

Centenarians themselves report using three main coping strategies to deal with the stress of health problems: acceptance, not worrying and taking things one day at a time.

Many of the neuroendocrine changes that occur with aging are not inevitable, said Epel, and "this is demonstrated by healthy centenarians. Certain age-related changes can be modified with physical activity, sufficient sleep and good coping techniques. It is when chronic stress, inactivity and added body weight take hold that the neuroendocrine system becomes off balance. This imbalance between the anabolic and catabolic hormones now appears to be the most common profile of aging and may be a valuable marker for biological aging."

Both of these reviews will be presented at the 114th Annual Convention of the American Psychological Association (APA) on August 11 and 12, 2006.