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Loneliness actually hurts us on a cellular level

A scientist explains how the pain of loneliness makes us sick. / Shutterstock
Brian Resnick is Vox’s science and health editor, and is the co-creator of Unexplainable, Vox's podcast about unanswered questions in science. Previously, Brian was a reporter at Vox and at National Journal.

“Humans are social animals” is a phrase often repeated by psychologists to sum up why we’ve been such a successful species. Our ability to live, work, and cooperate in groups is the key to our survival.

But it comes with a tradeoff. Companionship is an asset for human survival, but its mirror twin, isolation, can be toxic.

Loneliness is associated with higher blood pressure and heart disease — it literally breaks our hearts. A 2015 meta-review of 70 studies showed that loneliness increases the risk of your chance of dying by 26 percent. (Compare that to depression and anxiety, which is associated with a comparable 21 percent increase in mortality.)

Now researchers are trying to understand exactly how loneliness causes disease at the cellular level. And they’re finding that loneliness is far more than a psychological pain — it’s a biological wound that wreaks havoc on our cells.

“Social isolation is far and away the strongest social risk factor out there,” Steve Cole, a genetics researcher at the University of California Los Angeles, tells me. Or, as John Cacioppo, a University of Chicago psychologist who frequently collaborates with Cole on loneliness studies, has said, “The level of toxicity from loneliness is stunning.”

I called Cole to learn how loneliness can make us sick — and what that means for the 40 percent of people age 65 and older who report being lonely at times. I was also thinking about this GIF of how America will age until 2050. It's a wave of increasing old age, but it may also represent a soul-crushing wave of loneliness as baby boomers age into their 70s.


How does a feeling like loneliness influence our biology?

In 2007, Cole and a team of researchers at UCLA make a breakthrough in a small 14-participant study. The very cells of people who lived through periods of chronic loneliness looked different.

More specifically, the white blood cells of people who suffered through chronic loneliness appeared to be stuck in a state of fear. Cole and his colleagues observed two main genetic differences between lonely and non-lonely people.

1) Genes that code for the body’s inflammation response are turned on to a degree not seen in non-lonely participants.

Which isn’t good. “Inflammation is great at responding to acute injury, but if you have inflammation going chronically, it serves as a fertilizer for chronic diseases like atherosclerosis and cardio vascular disease, neurodegenerative diseases, and metastatic cancer,” he says. “That provides one reasonable biological explanation for why they might be at an increased risk for these diseases.”

2) “At the same time, in almost like a teeter-totter regulatory dynamic, we see down-regulated, or suppressed activity, in a block of genes involved in fending off against viral infections.” Those genes code for proteins known as type-1 interferons, which direct the immune system to kill viruses.

This is a bit of a head-scratcher. Increasing the body’s inflammation response in the face of stress makes sense. It’s protective in the short term. But why would our bodies become less willing to attack viruses?

Cole says it’s essentially a biological tradeoff. The inflammation response is how the body attacks bacteria. And it so happens that the body’s response to viruses can actually make bacteria thrive. So the body makes a choice — and it’s all in the name of protecting against bacteria. (Cole says there’s more nuance to it, but this is the basic concept.)

Overall, Cole finds, the response to chronic loneliness isn’t different than the response to other sources of chronic stress — like low socioeconomic status or living with post-traumatic stress. “You see the same general molecular pattern across a diverse range of bad human life circumstances,” he says. Loneliness activates the body’s generic stress response.

When we’re stressed, our bodies release the hormones epinephrine and cortisol, and when those are in the blood, they activate the genetic changes mentioned above (through a long chain of action, read more on that here). And, in the long term, that response harms us.

In all, the results — which have been replicated in larger and more longitudinal studies — suggest people who are lonely are more susceptible to chronic diseases, and less able to fight off immediate threats. And that may explain the increase in mortality among lonely people. (It’s not the sole reason, however. Having friends around makes life easier. They drive you to doctors’ appointments. They help you through tough times.)

Loneliness is a vicious cycle. The more isolated we are, the more threatened we feel. The more threatened we feel, the more we seek isolation.

We still don’t have great ways to avert loneliness

In longitudinal studies that track people over a period of time, Cole and his colleagues find that when feelings of loneliness wane, so do the cellular symptoms. And there are small preliminary studies that offer some hope that reducing loneliness also reduces the impact of these cellular changes.

Cole says the evidence that interventions can help people become less lonely is currently only “modest. … I’m not impressed with the magnitude of the effects.” Interventions that work tend to not target decreasing loneliness, he says, but instead try to give people a sense of purpose. One pilot program pairs lonely older Americans with elementary school children. The older participants are told to tutor and look out for the kids. “Secretly, this is an intervention for the older people,” he says.

Make no mistake: We need stress. We need loneliness. The pain of loneliness is a reminder that we need to be around other people. And there’s evidence that suggests loneliness naturally rises and falls throughout our lifetimes.

Cole says when he first started to study loneliness, he discounted its destructive power. But he is now convinced it’s a silent epidemic. It’s a larger risk factor for disease than “other things we spend more time worrying about;” things like anxiety and depression, he says.

Loneliness increases with age. And an aging wave of baby boomers means a wave of loneliness is coming for America.

After he published that first 2007 study, he started to get notes from “lonely people being devoured by disease and suffering, both personal and somatic,” he says. “There is a huge hidden epidemic of loneliness and disenfranchisement from the human race.”

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