While previous research has demonstrated the negative impact loneliness can have on health, the mechanisms underlying this association have been unclear. Now, a new study sheds light on the issue, finding that loneliness can alter immune system cells in a way that increases susceptibility to illness.

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Researchers say their study helps explain why loneliness can lead to poor health and early death.

The study - published in the Proceedings of the National Academy of Sciences - was conducted by John T. Cacioppo, professor of psychology at the University of Chicago, and colleagues from the University of California-Los Angeles (UCLA) and the University of California-Davis.

The research builds on a previous study conducted by Prof. Cacioppo last year, which found that older adults who experience extreme loneliness are at 14% greater risk for premature death.

Another study reported by Medical News Today earlier this year expanded on such findings, revealing that loneliness and social isolation experienced at any age can increase the risk of early mortality.

These studies and others say loneliness increases the risk for early death by triggering chronic illness, but Prof. Cacioppo and colleagues note that the molecular mechanisms underlying the health effects of loneliness are poorly understood.

Loneliness triggers CTRA gene expression in white blood cells

Previously, the team found that people who were lonely had greater inflammation and a weaker immune response than those who were not lonely, suggesting loneliness may be associated with a mechanism known as "conserved transcriptional response to adversity" (CTRA).

CTRA is characterized by an increase in expression of genes that play a role in inflammation and a decrease in expression of genes involved in antiviral response.

Prof. Cacioppo and colleagues delved deeper in this latest study, analyzing the gene expression in leukocytes - white blood cells in the immune system that help stave off infection - of 141 adults aged 50-68 who were part of the Chicago Health, Aging and Social Relations Study.

Confirming their previous research, the team found that individuals who were lonely demonstrated greater CTRA gene expression in their white blood cells than non-lonely individuals.

However, they also found that loneliness predicted CTRA gene expression measured at least 1 year later, while CTRA gene expression predicted loneliness measured a year or more later. This indicates that leukocyte gene expression and loneliness work together to exacerbate each other over time.

CTRA gene expression fueled by disrupted 'fight-or-flight' signaling

The researchers also analyzed the gene expression in leukocytes of rhesus macaque monkeys, which they note are a highly social species. The monkeys were from the California National Primate Research Center - a center deemed high in perceived social isolation.

Not only did lonely monkeys demonstrate greater CTRA gene expression in their white blood cells, but they also had higher levels of the neurotransmitter norepinephrine, which is involved in the "fight-or-flight" response to stress.

Fast facts about loneliness
  • A 2010 survey of more than 3,000 adults in the US found that more than a third of respondents aged 45 and older were categorized as lonely
  • Younger adults aged 45-49 reported higher rates of loneliness than adults aged 70 and older
  • Lonely adults were significantly more likely to report poor health than non-lonely adults.

Past research has shown norepinephrine can increase production of immature monocytes - a type of white blood cell - in bone marrow. These monocytes demonstrate high inflammatory gene expression and low antiviral gene expression.

The team found that both lonely monkeys and humans had higher levels of monocytes in their blood. Further investigation found this is due to an increase in production of immature monocytes; monkeys repeatedly exposed to mild social stress experienced a rise in levels of these cells.

Overall, the researchers say their findings suggest loneliness disrupts fight-or-fight signaling, which leads to increased production of immature monocytes, causing lower antiviral responses and increased inflammation. In turn, this may impair the production of white blood cells, partly explaining why lonely individuals are at greater risk for chronic illness.

The team demonstrated that such a mechanism can have severe implications for health. In a separate experiment, lonely monkeys with impaired antiviral gene expression that were infected with simian immunodeficiency virus (SIV) - the equivalent to HIV in humans - experienced faster growth of the virus in their blood and brain.

The investigators conclude that further research is required to determine the exact mechanisms by which impaired norepinephrine signaling increases immature monocyte production. The team also wants to learn more about how loneliness increases the risk of poor health and how such outcomes can be prevented.

In 2012, MNT reported on another study by UCLA researchers that found meditation may help reduce loneliness and its associated health effects.