Past low social status leaves long-lasting scars in the immune system, new study finds

Rhesus macaque family
Adult rhesus macaque monkeys' previous status in their community's social hierarchy has a lingering effect on how their genes behave.

New research suggests that the chronic stress that comes with low social status in adult monkeys continues to influence their immune system up to a year later, even after their social status has improved. The study by researchers at the University of Chicago and Duke University found that the adult monkeys’ previous status in their community’s social hierarchy had a lingering effect on how their genes behaved.

The findings extend established ideas around biological embedding, which suggest that it is experiences in the first few years of our lives – such as being raised in a safe, caring environment, versus one that involves abuse – that are more likely to leave long-term effects on our biology and development.

“Events that occurred in adulthood can also have a long-term impact on the function of your cells and biology of your system,” said study co-author Luis Barreiro, PhD, a University of Chicago geneticist. “Somehow, the cells in our body remember something about our social experiences, even though they may have happened months or up to a year ago.”

The study was published this week in the Proceedings of the National Academy of Sciences.

Chronic stress and health

Previous research already suggests that chronic stress can affect the immune system’s ability to fight an infection or respond to pathogens. In humans, chronic stress is strongly correlated with socioeconomic factors, such as how much money people earn, where they live and how well educated they are. In the United States, people living in the highest socioeconomic stratum can live roughly ten years longer than a person born in a low socioeconomic status.

Studying how socioeconomic factors impact health in humans is complex, however, because of the many other variables (such as diet or health care) that must be taken into account. By studying 45 adult female rhesus macaques at the Yerkes National Primate Research Center of Emory University in Atlanta, the researchers were able to keep these variables constant, while purposefully manipulating social status.

Somehow, the cells in our body remember something about our social experiences.
Rhesus macaques are known for what primatologists call “despotic behavior” – they live in defined hierarchical communities that shape everyday life and are enforced through both non-aggressive and aggressive methods. Whether a monkey is high or low in social rank determines the amount of resources they can access and can even predict how many babies they have. For instance, low status monkeys have fewer grooming opportunities, which are critical for making friends with other monkeys and relaxation.

“In this system, social rank is a proxy for chronic stress in humans,” Barreiro said. “If you’re a low ranking monkey, you’ll receive more harassment from others.”

The unrelated monkeys were first placed in nine new social groups, only to have their social rank changed after a year. In both cases, females who were placed into groups first became higher status. But high status monkeys from the original groups were placed together in the second round, resulting in some of them falling in status. Meanwhile, low status monkeys from the first round were also placed together — meaning that some hit the jackpot and became the highest-ranking in their new groups.

Downstream genetic effects

Blood samples taken after the status switch were then exposed to agents that mimic an infection with a bacteria or a virus. The researchers then measured how the cells responded to those immune stimulations. A study published in 2016 by Barreiro and Duke University evolutionary anthropologist Jenny Tung, PhD, found that rhesus macaques’ social status affected how thousands of genes turned on and off, especially those involved in fighting infections. In low status monkeys, some genes went into overdrive, causing inflammation.

The team’s latest study shows that a monkey’s past social rank continues to influence their genes; specifically, they found 3,735 genes continued to be affected by a monkey’s past rank, irrespective of their current status.

“We all have baggage,” said co-author Tung. “Our results suggest that your body remembers having low social status in the past, and it holds on to that memory much more than it would if things had been really great.”

The study, “Social History and Exposure to Pathogen Signals Modulate Social Status Effects on Gene Regulation in Rhesus Macaques,” was supported by the National Institutes of Health, the National Science Foundation, the Canada Research Chairs Program, the Natural Sciences and Engineering Research Council of Canada and the North Carolina Biotechnology Center. Additional authors include Joaquín Sanz of the University of Montreal, Paul Maurizio of the University of Chicago, Noah Snyder-Mackler, Noah Simons and Tawni Voyles of Duke University and Jordan Kohn, Vasiliki Michopoulos and Mark Wilson of Emory University.