Researchers also blame stress's ability to impede the delicate dance of chemicals that keep the body functioning smoothly. Recent studies especially implicate chemicals involved in fat storage, the immune system, and the longevity of cells themselves. Among the most important findings for long-term health:
• Telomerase. Perhaps the most intriguing discovery focuses on this enzyme, which is so important to cell health that the researchers who discovered it were awarded the Nobel Prize in 2009. Likened to plastic shoelace tips, telomeres are caps on the ends of chromosomes that shorten each time a cell divides; when they become very small, the cell dies. An enzyme called telomerase adds some length back to the telomeres. Levels of telomerase seem to be enhanced by stress reduction techniques like yoga and meditation, while high levels of stress have been linked to premature telomere contraction. (This was the measure of cell aging used in the studies of stress in childhood and in utero.) In a landmark 2004 study by Elissa Epel and colleagues at the University of California–San Francisco, for example, women who felt the most stressed while caring for a chronically ill child had telomere lengths indicating their cells were 10 years older than those of the least stressed mothers. Shorter lengths predict a variety of the diseases of aging, from arthritis and diabetes to neurodegenerative diseases like dementia, says Epel, an associate professor of psychiatry.
•Cortisol. Scientists continue to uncover the myriad ways this key stress hormone damages the body. Chronically high levels are now known to trigger insulin resistance, a precursor to diabetes. Spiegel, who regularly works with cancer patients, says cortisol is thought to be involved in that disease as well by interfering with expression of tumor suppressor genes. "By inhibiting suppression of certain cancer-related genes, there is some evidence that abnormal cortisol can increase the rate of cancer progression," he says. Excess cortisol also affects the heart, and at least one study links it to premature death. When Dutch researchers followed more than 800 people 65 and older for six years, they found that those with the highest cortisol levels at the start of the study were five times as likely to die of cardiovascular disease in the subsequent years as those with the lowest levels, they reported in 2010. This was true even in people with no signs of heart trouble when the study began.
•Neuropeptide Y (NPY). A decade ago, UCSF researcher Epel made headlines when her lab discovered that chronic stress causes people to pack on dangerous deep belly or "visceral" fat, the kind linked to cardiovascular and other diseases. Since then, other researchers have identified NPY, a neurotransmitter in the brain and body that regulates energy use, as the prime culprit. Under stress, NPY sends messages to the abdomen to both store fat there and recruit other cells to transform themselves into fat. This makes sense from an evolutionary standpoint, Epel says, because substances in belly fat are more easily converted to the energy needed to outrun a predator than those in the fat stored around the thighs and buttocks. This effect often combines with the desire to seek out the dense calories of comfort food when unnerved, another adaptive stress response (this one to famine). It also at least partly explains society's expanding waistlines, Epel says.
• Inflammatory molecules. Bouts of stress also trigger proteins like cytokines that activate an inflammatory response in the body. "We think that happens to protect the body from injury that might occur while it is fighting or fleeing," explains Philip Gold, a senior investigator at the National Institute of Mental Health, who codirected the Washington conference. Short-term inflammation is actually a good thing, since it prevents infection and, by increasing blood flow and releasing numerous compounds, starts the healing process. But over a prolonged period, too much inflammation is believed to play a role in promoting a host of medical conditions, including heart disease.