Loneliness is more than a feeling: for older adults,
perceived social isolation is a major health risk
that can increase the risk of premature death by 14
percent.
Researchers have long known the dangers of
loneliness, but the cellular mechanisms by which
loneliness causes adverse health outcomes have not
been well understood. Now a team of researchers,
including Chicago psychologist and leading
loneliness expert John Cacioppo, has released a
study shedding new light on how loneliness triggers
physiological responses that can ultimately make us
sick.
The paper, which appears Nov. 23 in the Proceedings
of the National Academy of Sciences, shows that
loneliness leads to fight-or-flight stress
signaling, which can ultimately affect the
production of white blood cells.
Along with Cacioppo, the research team includes
Steven W. Cole of UCLA and John P. Capitanio of the
California National Primate Research Center at the
University of California, Davis. The study examined
loneliness in both humans and rhesus macaques, a
highly social primate species.
Previous research from this group had identified a
link between loneliness and a phenomenon they called
"conserved transcriptional response to adversity" or
CTRA. This response is characterized by an increased
expression of genes involved in inflammation and a
decreased expression of genes involved in antiviral
responses. Essentially, lonely people had a less
effective immune response and more inflammation than
non-lonely people.
For the current study, the team examined gene
expression in leukocytes, cells of the immune system
that are involved in protecting the body against
bacteria and viruses.
As expected, the leukocytes of lonely humans and
macaques showed the effects of CTRA--an increased
expression of genes involved in inflammation and a
decreased expression of genes involved in antiviral
responses. But the study also revealed several
important new pieces of information about
loneliness' effect on the body.
First, the researchers found that loneliness
predicted future CTRA gene expression measured a
year or more later. Interestingly, CTRA gene
expression also predicted loneliness measured a year
or more later. Leukocyte gene expression and
loneliness appear to have a reciprocal relationship,
suggesting that each can help propagate the other
over time. These results were specific to loneliness
and could not be explained by depression, stress or
social support.
Next, the team investigated the cellular processes
linking social experience to CTRA gene expression in
rhesus macaque monkeys at the California National
Primate Research Center, which had been behaviorally
classified as high in perceived social isolation.
Like the lonely humans, the "lonely like" monkeys
showed higher CTRA activity. They also showed higher
levels of the fight-or-flight neurotransmitter,
norepinephrine.
Previous research has found that norepinephrine can
stimulate blood stem cells in bone marrow to make
more of a particular kind of immune cell--an
immature monocyte that shows high levels of
inflammatory gene expression and low levels of
antiviral gene expression. Both lonely humans and
"lonely like" monkeys showed higher levels of
monocytes in their blood.
More detailed studies of the monkey white blood
cells found that this difference stemmed from
expansion of the pool of immature monocytes. In an
additional study, monkeys repeatedly exposed to
mildly stressful social conditions (unfamiliar
cage-mates) also showed increases in immature
monocyte levels. These analyses have finally
identified one reason why CTRA gene expression is
amplified in the white blood cell pool: increased
output of immature monocytes.
Finally, the researchers determined that this
monocyte-related CTRA shift had real consequences
for health. In a monkey model of viral infection,
the impaired antiviral gene expression in "lonely
like" monkeys allowed simian immunodeficiency virus
(the monkey version of HIV) to grow faster in both
blood and brain.
Taken together, these findings support a mechanistic
model in which loneliness results in fight-or-flight
stress signaling, which increases the production of
immature monocytes, leading to up-regulation of
inflammatory genes and impaired anti-viral
responses. The "danger signals" activated in the
brain by loneliness ultimately affect the production
of white blood cells. The resulting shift in
monocyte output may both propagate loneliness and
contribute to its associated health risks.
The team plans to continue research on how
loneliness leads to poor health outcomes and how
these effects can be prevented in older adults.
For more information
PNAS - Proceedings of the National Academy of
Sciences
Myeloid differentiation architecture of leukocyte
transcriptome dynamics in perceived social isolation
Link...
MDN |