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In Selye's mind, stress was any kind of crisis in the body, any demand or damage, from starvation or sleep deprivation to a strenuous muscular workout, an infection, or a fear-provoking event. These days, scientists tend to define a stressor as something that disrupts the body's homeostasis, and the stress response as the myriad adaptations that eventually restore the balance. If the disruption is short-lived, the body usually recovers from it quickly.

But the stress response was not fashioned with the prospect of modern life in mind, says Bruce McEwen, the barrage of one stressor after another that seems to characterize contemporary existence. Our bodies have trouble telling the difference between an immediate, life-threatening danger and, say, perpetual quarreling with family or the ongoing grind of money worries. As McEwen suggests, a hand-to-hand struggle or quick dash to safety is not an appropriate response to an angry spouse or an insufficient paycheck. These kinds of common stresses can build up over the course of a day, a week, a year, and the stress response gets stuck in high gear until the mechanisms that are supposed to help us eventually begin to betray us. Moreover, we often make the wrong choices in response to such relentless stress, says McEwen. We eat more rich food, drink more alcohol, work harder, put in longer hours, stay up too late, stop exercising, and end up feeling even more even anxious, exhausted, ill.

A few weeks after the 9/11 terrorist attacks, I gave an afternoon lecture to medical students at the University of Virginia about recent discoveries in genetics and their effect on personal choices in medicine. It had been a difficult month. My nephew, a young man studying finance who was on his first trip to New York, had been in the south tower when it was struck. By some miracle he got out. So many did not. The days in the wake of the attacks brought waves of worry and grief. Like others, I struggled through the days and slept only fitfully, finding it difficult to concentrate and falling behind in my work. I was nervous about this talk, about taking on a subject with so much scope and complexity and not having time to prepare. To pull it together, I dispensed with exercise, decent eating, family time, and rest.

At the start of the lecture I felt confident, if a little warm and flushed, a sensation I wrote off as excitement and the effects of adrenaline. Slightly elevated body temperature is not a bad thing under normal circumstances, and indeed has been linked with improved performance (possibly, say some scientists, because raised body temperature enhances neurobehavioral function). But it's a matter of degree. When temperature exceeds about 101° F, mental and physical functions deteriorate. During the question-and-answer period after the talk, I began to feel woozy and confused, and I responded to the students' intelligent queries with vague, distinctly unintelligent responses.

"Does that answer your question?"

Not likely.

When I got home, I found I had a temperature of 103° F. It was the beginning of a bad case of pneumonia that put me in bed for a month.

As early as the 1900s, Sir William Osier noted that stress in the form of frenetic living may make us sick, but only recently has a rash of new studies offered concrete evidence for the way psychological stress may affect susceptibility to all sorts of diseases. Hormones are a key to the link. Excessive stress disrupts the normal circadian rise and fall of hormones, flattening the curves at their peak. A small, temporary dose of stress hormones is generally a good thing for the body, says McEwen; big, long-term doses are not. Constant high levels of adrenaline raise blood pressure, which can create scars or lesions in the blood vessels of the heart and brain where artery-clogging material called plaque builds up.

Too much Cortisol can be equally deadly, causing bone loss and increased abdominal fat. The raised Cortisol levels that come with chronic stress actually step up the rate at which our food is turned into fat and govern where that fat goes. McEwen and his colleague Elissa'S. Epel, a researcher at the University of California at San Francisco (UCSF), found that the increased Cortisol levels experienced by women under stress led to great accumulations of abdominal fat, even in otherwise slender women. The hormone turns on fat receptors in the abdomen and belly so that fat deposits build up there rather than on hips and buttocks—which heightens the risk for heart disease, diabetes, and stroke. Excessive Cortisol also makes the liver produce more glucose for energy, McEwen explains. Normally the liver releases a lot of glucose at night. When that typical dose is boosted by cortisol, the excess circulates all night while we're at rest and not using it, setting our bodies on the path to weight gain, insulin resistance, and diabetes.

To make things worse, we often respond to long-term stress by seeking to self-medicate with high-fat food. In the days after 9/11, I shunned my usual healthy fare and dove with gusto into banana bread, pasta, chocolate chip cookies, anything full of fat or sugar. My friends, I soon learned, were doing the same. It's a common response to feeling strung out, seeking the calm produced by comfort food. "Stress makes us hungry," says McEwen.

Until lately, there was plenty of anecdotal evidence that eating that brownie or chocolate bar might temporarily soothe the nervous soul but little in the way of scientific confirmation. That changed with research from UCSF showing that the signals the body sends out after consuming high-calorie foods can temporarily ratchet back the activity of the stress hormone system. With long-term chronic stress, however, the excess calories can mean a hefty addition of extra fat—and an inability to bounce back from a stressful event. When scientists at the University of Maryland studied rats fed a high-fat diet for ten weeks, they discovered that the fat-fed rats recovered from stress much more slowly than rats kept on a normal diet.

Our immune system also suffers. Built to be sensitive to the signals of acute stress, immune cells carry receptors for Cortisol and other stress hormones so they can respond quickly to injury and potential infection. A single stressful event tends to rev up the system, enhancing its performance. But unremitting stress has the reverse effect. Some 150 studies suggest that incessant stress dampens the immune response and makes people more susceptible to infection. People who endure stressful conditions for more than a month—debilitating grief after the death of a family member, divorce, or loss of a job—are far more likely to come down with a cold than those less frazzled. They're also apt to produce a weaker immune response to a vaccine.

So, too, cumulative stress slows the healing of wounds. One study found that in women caring for a relative with Alzheimer's disease—a highly demanding job that requires intensive, exhaustive attention—small skin wounds took an average of nine days longer to heal than wounds in control subjects. Psychological stress, it turns out, inhibits a key component of the early stages of wound repair, the secretion of chemicals involved in healing known as proinflammatory cytokines.

Even more insidious, perhaps, is the effect of constant stress and vigilance on learning, memory, and the very structure of the brain. The hippocampus, a part of the brain crucial to memory, has many receptors for Cortisol and so is particularly vulnerable to hormonal excess. McEwen has shown that even temporary stress, if sufficiently severe, can shrivel the dendrites of hippocampal neurons, those long projections where the neurons receive signals. "This may be a protective mechanism against permanent damage," he says. "By withdrawing contact with other cells, the hippocampal cells may avoid being blown out permanently, like a circuit breaker." However, the hippocampus normally plays a part in shutting off the stress response by signaling the hypothalamus to stop producing stress hormones. So damage to the structure from long-term stress can result in the release of even more hormones, setting off a cycle of elevated hormones and further destruction.

A kind of reverse process goes on in the amygdala, with a similar nasty effect of raising anxiety and stress. Scientists have discovered that repeated stress makes neurons in the amygdala bloom with branching dendrites. This creates more low-road connections with sensory neurons and thus more routes of access for unconscious emotional information. As a result, even a small sensory component of a potentially fearful situation—an innocent detail taken in unconsciously—may trigger a burst of activity in the amygdala, heightening fear. As Joseph LeDoux sees it, this mechanism may account for certain types of "nameless" anxieties.

Perhaps most disturbing is news that stress frays our very DNA.

Look around your home or your office. Who looks drained and exhausted? Whose face sags? "People who are stressed over long periods tend to look haggard," says Elissa Epel of UCSF. We all know this intuitively. To figure out why it might be so, Epel and her team recruited fifty-eight mothers between the ages of twenty and fifty. Thirty-nine of the mothers were—like my own mother—primary caregivers for a child chronically ill with a disease such as cerebral palsy or autism. The women filled out a questionnaire to determine their perceived levels of stress. The team then studied the women's DNA, focusing on tiny structures called telomeres, which serve as timekeepers, informing the cell of its age. Telomeres cap the end of chromosomes like those little plastic caps on shoelaces, preventing the DNA within from unraveling. Every time a cell divides, a bit of its telomeres fray away. After many divisions, the telomeres are so reduced that the cell stops dividing and dies.

In 2004, the team published its remarkable results: Mothers who suffered the most perceived psychological stress had substantially shorter telomeres. They also had much-reduced activity of an enzyme called telomerase, which helps to preserve telomeres. Compared with the cells of unstressed women of the same chronological age, the cells of the high-stress mothers had "aged" the equivalent of nine to seventeen years. The scientists suspect that the underlying cause of this premature aging may be an overabundance of chemicals called free radicals—triggered by stress hormones—which hinder the activity of telomerase.

How your body responds to stressful events may be determined in part by your genes. Look around again at your friends and colleagues. Who worries every detail? Who goes with the flow? While one friend may fuss and fret about this hassle and that worry, another seems unfazed by anything. Most of us know someone who never feels strung out or anxious, someone who seems to seek out stressful experiences and relish danger.

My friend Miriam is one such fearless spirit. Petite but powerful and ever optimistic, she appears to sail through life's traumas with ease and resilience. In college, her friends called her "Mitomim," after mitochondria, those minute powerhouses inside our cells. Miriam seems happiest when she's pushing body and mind, running up Mount Washington, say, or pressing forward on a flood of different work tasks. One year, not long after her forty-fifth birthday, she climbed the sheer face of the Matterhorn during the dark hours of predawn and in the midst of an ice storm—just for the fun of it. The next year she suffered a head-on automobile collision that nearly killed her; when she came to, she said, her first thought was whether to ruin her husband's morning by calling him with the news.

Then there's Mary, for whom the smallest dose of stress, mental or physical, is so toxic it tips her into despair. Mary falls into the category of people who can't adjust to such mild traumas as public speaking or confronting a boss. In response to the everyday stresses of life, she overexposes her body to stress hormones.

What accounts for the gulf between merry Miriam and brittle Mary?

Not long ago, this might have been considered a barren thread of inquiry, the disparity written off as a matter of something as nebulous as temperament or human nature. But lately there has emerged what some may consider a possible biological underpinning for these differences. Whether or not we are derailed by life's stresses is influenced by certain genes—specifically, by the length of our so-called serotonin transporter genes. These genes, which come in two sizes, short and long, affect the expression of the mood-regulating chemical serotonin. The genes made headlines a few years ago, when scientists at the National Institute of Mental Health showed that the short version was weakly linked to neuroticism, a tendency toward anxiety, self-consciousness, moodiness, and low self-esteem, which earned it the moniker "the Woody Allen gene." People blessed with two long copies (about 30 percent of the population) are more apt to respond with resilience to a run of stressful life experiences. Those with two short copies (about 20 percent of people) are two and a half times more likely to suffer seriously from stress. The rest, bestowed with one of each version, are moderately vulnerable.

This is not to reduce Miriam's buoyant character to a single snippet of DNA. Nor is it to say that possessing a double dose of the long genes confers complete immunity from the effects of chronic stress. No single gene bears full responsibility for tolerance of stress or tendency to high anxiety; hundreds of genes likely figure into the mix. But the new research does suggest this: The interaction of genetic makeup (two short variants of the gene) and experience (major life stresses such as disabling injury, trouble in an intimate relationship, long-term unemployment) may put Mary at the susceptible end of the scale, more than doubling her chance of succumbing to stress-related ailments. And two long versions of the gene may give Miriam a relatively slim chance of suffering, no matter how many stressful episodes come her way.

So what's a worrier to do?

Try to feel in control of your situation, says Esther Sternberg, an expert on the science of emotions and health and the director of the Integrative Neural Immune Program at the National Institutes of Health. Feeling that you're in the driver's seat, so to speak—able to take action to affect your own fate—banishes feelings of helplessness and panic and reduces the effects of long-term stress.