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Salon
Salon
Science
Shilpa Ravella

How loneliness gets in your cells

When it began some three years ago, few anticipated that the COVID-19 pandemic would kill several million people and injure countless others. Patients suffered with traumatic intensive care unit stays that sometimes left them with scarred lungs and hearts, cognitive issues, failing kidneys and much more. The damage caused by COVID-19—even for those with an ostensibly mild illness — could continue long after recovery from the infection, causing lasting issues like fatigue, brain fog, loss of taste or smell, and chronic pain.

Yet the coronavirus pandemic did not merely wreak havoc upon our physical bodies, but also our mental health. As unemployment, food insecurity and burnout increased, the pandemic fractured relationships and intensified loneliness—which was a prevalent problem pre-pandemic as well. In 2019, 61% of Americans over the age of 18 reported being lonely, as compared to as low as 11% in the 1970s. Loneliness affects people of all ages: around 50% people over the age of 80 experience it, and so do 71% of adolescents and young adults. 

The health consequences of chronic loneliness, an intense stressor for a species adapted to tribal tendencies for survival, are pronounced.

Factors thought to have contributed to the high rates of modern loneliness include changes in the family structure; longer lives with increased incidences of loss of loved ones; a waning of community organizations that strengthen social capital;, and the excessive use or misuse of technology. The pandemic only exacerbated the problem. Today, over half of Americans have not returned to their pre-pandemic levels of social activity, and around the same number experience "holiday blues" due to loneliness. Loneliness is, as Arthur Brooks writes, a "pandemic habit." 

Loneliness, a subjective feeling of being "alone," differs from social isolation, or a dearth of social connections. Social isolation can indeed lead to loneliness, but this is not always the case. Meanwhile, some people can feel lonely even without being socially isolated. Loneliness and social isolation do occur together frequently, and both independently contribute to poorer health. 

The health consequences of chronic loneliness, an intense stressor for a species adapted to tribal tendencies for survival, are pronounced. Loneliness increases the risk of many illnesses, including heart disease, diabetes, some cancers, stroke, dementia, and mental health disorders like anxiety and depression. It predicts low functional status, increased rates of hospital admissions and readmissions, longer hospital stays, and premature death. 

The epidemic of loneliness in this country, according to United States surgeon general Vivek Murthy, is a "public health crisis on the scale of the opioid epidemic or obesity." A 2015 meta-analysis by researchers at Brigham Young University confirms that loneliness is indeed as deadly a risk factor as obesity, smoking or a sedentary lifestyle. 

Chronic loneliness alters the body on a cellular level.

How exactly does loneliness contribute to disease? The danger to one's survival from perceived loneliness can affect various processes in our body, including those involved in metabolism — which governs the conversion of food into fuel, among other things — as well as neurologic, endocrine, and immune responses. Our immune system, in fact, responds to loneliness as it would the threat of a deadly virus, producing more inflammatory cells and proteins. Ongoing loneliness may lead to chronic, low-level inflammation. While inflammation is generally a benevolent force meant to help us to fight germs and heal wounds, we know today that chronic "hidden" inflammation can have profound implications for our health. Indeed, chronic inflammation has been connected to all kinds of modern diseases. Notably, "hidden" forms of inflammation are an independent cause of heart attacks and strokes, as is elevated blood cholesterol.

Studies show that loneliness or social isolation has been tied to elevated blood levels of inflammatory molecules like CRP, IL-6, TNF-a and IL-1B. One recent observational study conducted in Denmark revealed that living alone for many years or undergoing several serial relationship breakups — including those due to the death of a partner — were strongly associated with increased CRP and IL-6 levels in middle-aged men. In another 2017 study evaluating middle-aged adults in the US, feeling lonely was associated with systemic inflammation, measured by increases in CRP and IL-6 levels. And a May 2020 meta-analysis found links between loneliness or social isolation and elevated levels of CRP and IL-6, respectively. 

Chronic loneliness alters the body on a cellular level. In a 2015 study led by University of Chicago psychology professor John Cacioppo and colleagues, researchers asked 141 elderly adults to report levels of social isolation. The team then measured the expression of over 400 genes related to the immune system that are expressed by white blood cells, or leukocytes. They found that individuals describing themselves as socially isolated had an increase in genes involved in inflammation, but a decrease in genes that help the body to defend against germs. When the researchers repeated the experiment in rhesus macaques — a highly social primate species, like humans — the findings persisted. The researchers noted that socially isolated humans and macaques had higher levels of the fight-or-flight neurotransmitter norepinephrine coursing through their bodies, which prompted the bone marrow to make more of a particular type of leukocyte known as a monocyte, or an immature macrophage. Macrophages are one of our first-line defenses against invading germs. In the lonely humans and animals, these cells expressed more genes related to inflammation but fewer genes related to fighting viruses.

People suffering from loneliness, then, not only experience chronic inflammation but also weaker immunity. Loneliness, like other forms of stress, leads to an increased risk of infectious diseases. It can directly affect the ability of immune cells to effectively combat germs. We know, too, that chronic, low-level inflammation itself can hinder immunity. 

Alarmingly, loneliness also reduces one's ability to generate an effective immune response to a vaccine. UCLA scientist Steven Cole, who was involved in the above study, states that social disconnection triggers around 200 genes to contribute to what he calls "a molecular soup of death." He calls loneliness "a fertilizer for other diseases," promoting low-level inflammation that can lead to heart disease, cancer, neurodegenerative diseases and more. 

The links between loneliness and inflammation can be complex. For example, there is evidence for a bidirectional relationship between the two. Studies show that while loneliness increases inflammation, the state of being chronically inflamed also exacerbates loneliness, creating an unfavorable feedback loop. Chronic inflammation leads to "sickness behaviors" like fatigue, loss of appetite and social withdrawal, which likely evolved to keep sick individuals from infecting others and to keep them focused on fighting their own illness rather than lesser concerns like searching for and digesting food.

Some studies may not account for the inflammatory behaviors that loneliness begets, like eating and sleeping poorly, failing to exercise, and using smoking and alcohol to self-soothe. Lonely individuals are also more likely to face additional inflammatory life stressors — like poverty — or to respond to stress more vehemently than their well-connected counterparts. A lonely person, for example, is likely to develop higher levels of inflammation when facing challenges at work than someone with plenty of social support.

While observational studies cannot definitively prove that loneliness causes inflammation, it is evident that loneliness and inflammation are intricately linked — and that inflammation may be one important biological mechanism by which loneliness leads to disease. However, more large-scale research is needed to determine exactly how loneliness affects health. 

In the quest to combat the loneliness epidemic, it's important to realize that loneliness is not a personal failing or solely an individual issue. It is a major public health concern. In 2016, the British government appointed a "minister of loneliness" to examine ways in which to decrease loneliness in the UK. The US has no such nationalized approach, and US healthcare providers typically lack information on resources they can provide for lonely patients. As Brigham and Young University professor of psychology and neuroscience Julianne Holt-Lunstad wrote earlier this month in the New England Journal of Medicine, "although the healthcare sector cannot solve this problem alone…addressing social isolation and loneliness does not detract from patient care — it is patient care."

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