A team of researchers led by the University of Chicago have discovered the molecular mechanism by which social isolation affects health and causes premature death. Loneliness triggers a fight-or-flight stress response that ends up affecting white blood cells production. The study was published in the journal Proceedings of the National Academy of Sciences.
The study included humans aged 50-68 from a longitudinal study started in 2002 and the highly social rhesus macaques. Previous studies with the human group allowed to identify a “conserved transcriptional response to adversity” or CTRA among lonely people, characterized by a decrease in the expression of antiviral genes and an increase in the expression of genes involved with inflammation. For the new study, the researchers analyzed white blood cells gene expression, in the human and macaque groups, and found the same patterns. But, besides from that, they found that loneliness could predict future CTRA gene expression, and vice versa: both phenomena feed on each other. Isolated macaques also showed high levels of the fight-or-flight response neurotransmitter norepinephrine.
Norepinephrine increases immature monocyte production
Previous research reports had discovered that high norepinephrine levels cause an increase in the production of a specific immune cell type, the immature monocytes. These cells are characterized, precisely, by a CTRA gene expression. Under stressful conditions, the pool of immature monocytes grows. The researchers found an elevated population of monocytes in the blood of lonely humans and monkeys. Subsequent experiments demonstrated that this is the cause of the general CTRA gene expression pattern found in them.
The scientists proved that the CTRA pattern really affects health. Monkeys with perceived social isolation that where injected with the simian immunodeficiency virus (SIV) suffered a faster viral expansion in blood and brain.
Based on their results, the team of John Cacioppo proposes a model where isolation-derived stress causes an increase in norepinephrine levels, which triggers the formation on immature monocytes with diminished antiviral response and increased expression of imflammatory genes, leaving an affected white blood cell population. These poor health conditions might create a feedback loop with loneliness.