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Loneliness: A Molecule?
It is already known that a person's social environment can affect his or her health, with those who are socially isolated - that is, lonely - suffering from higher mortality than people who are not.

Now, in the first study of its kind, published in the current issue of the journal Genome Biology, UCLA researchers have identified a distinct pattern of gene expression in immune cells from people who experience chronically high levels of loneliness. The findings suggest that feelings of social isolation are linked to alterations in the activity of genes that drive inflammation, the first response of the immune system. The study provides a molecular framework for understanding why social factors are linked to an increased risk of heart disease, viral infections and cancer.

Having previously established that lonely people suffer from higher mortality than people who are not lonely, researchers are now trying to determine whether that risk is a result of reduced social resources, such as physical or economic assistance, or is due to the biological impact of social isolation on the functioning of the human body.

"What this study shows is that the biological impact of social isolation reaches down into some of our most basic internal processes - the activity of our genes," said Steve Cole, an associate professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA and a member of the Cousins Center for Psychoneuroimmunology.

"We found that changes in immune cell gene expression were specifically linked to the subjective experience of social distance," said Cole, who is also a member of UCLA's Jonsson Comprehensive Cancer Center. "The differences we observed were independent of other known risk factors, such as health status, age, weight and medication use. The changes were even independent of the objective size of a person's social network."

Cole and colleagues at UCLA and the University of Chicago used DNA microarrays to survey the activity of all known human genes in white blood cells from 14 individuals in the Chicago Health, Aging, and Social Relations Study. Six participants scored in the top 15 percent of the UCLA Loneliness Scale, a widely used measure of loneliness that was developed in the 1970s. The others scored in the bottom 15 percent. The researchers found that 209 gene transcripts - the first step in the making of a protein - were differentially expressed between the two groups, with 78 being overexpressed and 131 underexpressed.

"Leukocyte (white blood cell) gene expression appears to be remodelled in chronically lonely individuals," Cole said.

Genes overexpressed in lonely individuals included many involved in immune system activation and inflammation. But interestingly, several other key gene sets were underexpressed, including those involved in antiviral responses and antibody production.

"These findings provide molecular targets for our efforts to block the adverse health effects of social isolation," said Cole.

"We found that what counts at the level of gene expression is not how many people you know, it's how many you feel really close to over time," he added.

In the future, Cole said, the transcriptional fingerprint the researchers have identified might become useful as a biomarker to monitor interventions designed to reduce the impact of loneliness on health.