In 2005, Steve Cole began to peer inside the cells of lonely people, training his sights on the activity of their genomes. Cole, a psychologist turned molecular biologist at the University of California, Los Angeles, was interested in how psychological stressors such as chronic social isolation could be bad for our health, increasing our susceptibility to certain diseases. Research had already implicated stress hormones, which are produced at higher-than-average levels in people who feel lonely for long stretches. But Cole wanted to know what was going in the genes, and not just one or two. He suspected that the expression of large collections of genes might be disrupted in people who consistently reported feeling isolated. "I had an abiding mistrust of one-gene answers because genes generally work in coordinated networks in cells," he says.
Cole teamed up with University of Chicago social psychologist John Cacioppo, who had already been tracking 166 healthy middle-aged adults for three years, periodically asking them how socially isolated they felt and gathering all manner of biomedical, psychological, social, and economic data. Cole and Cacioppo took blood samples from 153 of the study subjects and focused on the eight most socially secure people and the six loneliest, who had scored highest on the UCLA Loneliness Scale for the past three years. When Cole ran these 14 subjects' white blood cells through a microarray analysis, he spotted more than 200 genes that were expressed differently between the two groups. Many of the genes dialed up in lonely individuals were involved in inflammation, while the downregulated genes tended to be associated with antiviral response, antibody production, and restraint of inflammatory responses.
It was a tiny sample, but the implications of the study, published in 2007, were great: loneliness, it seems, shapes one's health by controlling the "dimmer switch" for whole networks of immune-related genes. Indeed, this overexpression of proinflammatory genes and suppression of anti-inflammatory and antiviral genes might explain why lonely people are more likely to succumb to a variety of diseases, and why HIV ravages socially isolated people more quickly than their more connected peers. "It was gratifying to see the story [of how loneliness affects health] move beyond the genotype to include the functional aspect of the genome," says Cacioppo.