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Chronic loneliness can wreak havoc on the body's defenses.

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Loneliness Is in the Genes

If, as Roy Orbison sang, "Only the lonely" know how you feel tonight, you may need a doctor. A new study shows that loneliness may change how certain genes in the body work, leaving chronically lonely people with less effective immune systems and lower defenses against disease. The results, if confirmed, could enable doctors to better prevent those ills for which the lonely are at greater risk, such as heart disease, infection, age-related dementia, and certain types of cancer.

Everyone feels lonely from time to time, but some people have it much worse. These individuals consistently feel lonely for years, often despite having friends and family. Researchers have long known that such chronically lonely people are less healthy. They suspected cortisol, a hormone that regulates the body's response to stressful or threatening situations, was to blame, because it's found in higher levels in people who feel isolated. But the mechanism remained a mystery, and one nagging question persisted: If inflammation drives most loneliness-linked diseases, how can cortisol, with its anti-inflammatory properties, be the culprit?

Steve Cole, a genomics researcher at the University of California, Los Angeles (UCLA), and colleagues tracked a group of 153 people in their 50s and 60s, in hopes they'd provide an answer. The team ranked the volunteers using the UCLA Loneliness Scale, a test that measures a subject's loneliness by their responses to statements such as "I'm alone in the world" and "There's no one I can count on," regardless of how many people they know or spend time with. The researchers then studied DNA from the white blood cells of eight people who scored in the top 15th percentile of loneliness and six who scored in the bottom 15th percentile.

Of the 22,000 human genes, 209 were abnormally expressed in the very lonely group. Most of these genes help control the body's immune response. In the loneliest, the response was haywire: Those that activate the immune system and inflammation were overexpressed, whereas those that regulate the production of antibodies and antiviral factors were underexpressed. The results explain why lonely people suffer from chronic inflammation in spite of their high levels of cortisol and are vulnerable to microbes, viruses, and other sources of tissue damage, the researchers say. The study, which appears in the current issue of the journal Genome Biology, is the first to reveal on a molecular level how loneliness puts people at risk for disease, says Cole.

"This is an absolutely remarkable study," says Robert Wilson, a neuropsychologist at the Rush University Medical Center in Chicago, Illinois, who helped establish the link between loneliness and dementia. Still, he says it would be "reassuring" to see the study repeated with more subjects, and he notes that the work leaves unanswered which comes first, the loneliness or the change in gene expression. "We're certainly a long way from that kind of specificity," says Wilson, "but studies like this may get us there."

Cole hopes doctors will someday be able to use the genetic markers his team discovered to identify at-risk patients and keep them healthier with anti-inflammatory drugs such as aspirin. "We can't change them into the happy, laughing life of the party," he says, "but we can keep them out of the coffin."

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