Science Blog
09/14/2007

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.

The 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 for Psychoneuroimmunology at UCLA; the John Templeton Foundation; and the James B. Pendleton Charitable Trust. Other authors included Louise C. Hawkley, Jesusa M. Arevalo, Caroline Y. Sung, Robert M. Rose and John T. Cacioppo.

The Norman Cousins Center for Psychoneuroimmunology at UCLA encompasses an interdisciplinary network of scientists working to advance the understanding of psychoneuro-immunology by linking basic and clinical research programs and by translating findings into clinical practice. The center is affiliated with the Semel Institute for Neuroscience and Human Behavior at UCLA and the Geffen School of Medicine at UCLA.
 

The researchers suspected that while the toll of loneliness may be mild and unremarkable in early life, it accumulates with time. To test this idea, the scientists studied a group of college-age individuals and continued an annual study of a group of people who joined when they were between 50 and 68 years old.

Their findings, reported in the August issue of Current Directions in Psychological Science, a journal of the Association for Psychological Science, are revealing. Consider stress, for example. The more years you live, the more stressful experiences you are going to have: new jobs, marriage and divorce, parenting, financial worries, illness. Its inevitable.

However, when the psychologists looked at the lives of the middle-aged and old people in their study, they found that although the lonely ones reported the same number of stressful life events, they identified more sources of chronic stress and recalled more childhood adversity. Moreover, they differed in how they perceived their life experiences. Even when faced with similar challenges, the lonelier people appeared more helpless and threatened. And ironically, they were less apt to actively seek help when they are stressed out.

Hawkley and Cacioppo then took urine samples from both the lonely and the more contented volunteers, and found that the lonely ones had more of the hormone epinephrine flowing in their bodies. Epinephrine is one of the bodys fight or flight chemicals, and high levels indicate that lonely people go through life in a heightened state of arousal. As with blood pressure, this physiological toll likely becomes more apparent with aging. Since the bodys stress hormones are intricately involved in fighting inflammation and infection, it appears that loneliness contributes to the wear and tear of aging through this pathway as well.

There is more bad news. When we experience the depletion caused by stress, our bodies normally rely on restorative processes like sleep to shore us up. But when the researchers monitored the younger volunteers sleep, they found that the lonely nights were disturbed by many micro awakenings. That is, they appeared to sleep as much as the normal volunteers, but their sleep was of poorer quality. Not surprisingly, the lonelier people reported more daytime dysfunction. Since sleep tends to deteriorate with age anyway, the added hit from loneliness is probably compromising this natural restoration process even more.

Loneliness is not the same as solitude. Some people are just fine with being alone, and some even see solitude as an important path to spiritual growth. But for many, social isolation and physical aging make for a toxic cocktail.