Loneliness Is A Molecule

It's already known that a person's social environment can affect their 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, researchers are now trying to determine whether that risk is a result of reduced social resources, such as physical or economic assistance, or from the biological impact of social isolation on the function 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-Oncology at the David Geffen School of Medicine, and a member of the UCLA 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 the 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 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," said. Cole.

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." In the future, he said, the transcriptional fingerprint they've identified might become useful as a 'biomarker' to monitor interventions designed to reduce the impact of loneliness on health.

This study was supported by the National Institutes of Health, the Mind, Body, Brain and Health Initiative of the John D and Catherine T MacArthur Foundation, the Norman Cousins Center at UCLA, the John Templeton Foundation, and the James B Pendelton Charitable Trust. Other authors included Louise C Hawkley, Jesusa M Arevalo, Caroline Y Sung, Robert M Rose, and John T Cacioppo.

Reference: Steve W. Cole, Louise C Hawkley, Jesusa M Arevalo, Caroline Y Sung, Robert M Rose and John T Cacioppo "Social Regulation of Gene Expression in Humans: Glucocorticoid Resistance in the Leukocyte Transcriptome"  Genome Biology (in press)