The study found that it didn't matter whether the participants were healthy at the time of the study. “People say all the time, ‘Is it that being lonely makes you unhealthy, or is it

because you're unhealthy that you withdraw from others or they withdraw from you?’ “ Holt-Lunstad notes. “Certainly, physical and mental health issues can put you at risk for loneliness

and isolation, but the evidence we have is independent of health status. Whether or not you are healthy, those who are more socially connected live longer.” Conclusions like

Holt-Lunstad's are drawn by analyzing dozens of longitudinal studies — elegantly designed research projects that follow groups of individuals over long periods and track the development

subject than the ones found in sad songs or advice columns. Researchers require a way to measure loneliness, to distinguish between the feelings summoned by a failed romance or strange faces

in an unfamiliar city and those that reflect a chronic, intractable longing for a connection that isn't there. "That's one of the first issues we run into when scientists

talk about loneliness,” Hawkley says. “At what point do you say that somebody's lonely?” A teenage boy alone on a Saturday night experiences a very different kind of loneliness than

does an elderly man who lives in a bare apartment and hasn't spoken to anyone for days. Because loneliness can mean different things to different people, Hawkley says, scientists need

to measure the condition in a “more finely grained fashion, a continuum on which one can define an individual as being slightly, moderately or extremely lonely.” That continuum is found in

the UCLA Loneliness Scale, the gold standard for defining loneliness for research purposes. There are now several shortened versions of the scale, but the original is a 20-item questionnaire

that asks about feelings associated with loneliness but never inquires about loneliness per se. The questions include statements such as, “I am unhappy doing so many things alone,” and

“There is no one I can turn to.” The way in which the questions are worded, and the choice of answers, means that those who are fleetingly lonely or perfectly content in their solitude will

end up with scores at the low end of the scale, whereas the chronically lonely, at whom much of the research is aimed, will have scores putting them at the top. HOW BEING LONELY AFFECTS YOUR

BRAIN Not all scientists are studying loneliness as a complex matrix of contributing factors. A growing number are focusing on the feeling itself, the intensely personal experience of

rejection, disconnection and longing that some researchers believe produces a pain as real as any caused by a physical injury, one that has little to do with living arrangements or social

networks. These researchers are looking at loneliness as the nexus where molecular biology and psychology intersect, creating an intricate dance in which body and mind take their cues from

each other and produce a highly personal, private and prolonged kind of hell. Research along these lines stems from very basic questions: What's the point of loneliness? What purpose

could it possibly serve? Well, for one thing, it protects us from saber-toothed cats. Our earliest ancestors were sociable creatures — they had to be. Those on their own were vulnerable to

attack, easy pickings for hungry predators. According to this evolutionary model, loneliness may have evolved as a kind of early-warning system, a signal that something isn't right,

which prompted us to get back to the safety of the group and put the body in a stressful state of high alert until we did so. The sense of threat that would accompany such a feeling found

its way deep into our cellular makeup — inflammation like what geneticist Steve Cole found in the blood cells of the lonely people he studied. On a temporary basis, inflammation is a good

thing; it's the body's first system of defense, helping to combat an infection or repair a wound. But what works as a short-term response can be deadly when it's ongoing. 

Inflammation amps up biological processes leading to tissue breakdown and impairment of the immune system, which, in turn, increases our susceptibility to conditions ranging from heart

disease to Alzheimer's. "We think that human psychology interprets loneliness as a kind of threat, and that this kind of inflammatory response is a biological reflex that gets

triggered whenever we experience threat or uncertainty,” Cole explains. Inflammation then sets up a vicious cycle. “When you feel lonely, your brain activates inflammation in the white blood

cells,” he says. “Well, one of the weird things we've discovered is that inflammation talks back to the brain and changes the way it works.” What appears to happen? “After loneliness

stimulates that white blood cell inflammatory response, the response feeds back to the brain and makes it irritable, suspicious, prone to negative emotions and fearful of meeting new people

and making new friends." Those negative emotions set up an intricate loop of psychological responses, says Stephanie Cacioppo, director of the Brain Dynamics Laboratory at the

University of Chicago Pritzker School of Medicine. What's happening, she observes, amounts to a kind of duel between body and brain. The body, responding to millions of years of

evolutionary conditioning, wants to be with other people, but the modern, lonely brain, under the influence of the inflammatory response and heightened levels of stress, senses a threat in

its encounters with others and chooses to isolate us further. "Your body has a different survival mode than your brain has,” notes Cacioppo. “While the body has a long-term

self-preservation mode and wants to approach others to survive, the lonely brain has a short-term self-defense mode and sees, erroneously, more foes than friends.” In the lonely state, “the

brain is misreading social signals that it should read normally; suddenly it doesn't have the correct translation. You put someone who is lonely into a room alone and every person who

comes there will be perceived as a threat.” Lonely people, she continues, often misread a facial expression or tone of voice — characterizing curiosity as hostility, for instance — and

gradually develop a distorted reality about the social world around them. That unconscious sense of threat can lead to an endless behavioral cycle in which a lonely person, in a mistaken

attempt at self-protection, sends out signals of disinterest or even hostility, which then causes others to withdraw. Those who are lonely live at such a heightened level of alarm that they

lose sleep. Their brains also respond with greater alarm to words such as “reject” and “bully” than they do to other negative words, like “vomit.” And in one of the lab's recent

behavioral studies, married lonely people stood farther away from loved ones, reflecting their preference for greater interpersonal distance.