The Scicurious Brain

The Scicurious Brain

The Good, Bad, and Weird in Physiology and Neuroscience

Life at the bottom is bad for your health


Or at least, it's bad for the gene expression in the immune systems of female rhesus monkeys.


Social environment can have effects on your health. People (and animals) in bad social conditions are more susceptible to illness, and bad social situations can lead long term to issues like fertility or even survival. We've known about the correlation between social stress and health for a while, but most of what has been studied in humans about social environment and health has been correlational. You can't really determine whether the social environment alone creates the problems. But if you have an animal model, it's a lot easier to manipulate social environment, and to then look directly at the effects of social environment on various health measures. Using an animal model allows you not only to separate out social environment from other variables, it also allows you to look at mechanism, and try to see what changes in what areas produce the global susceptibility to illness and other problems associated with social stress.

In order to study the effects of social status directly, the authors Tung et al used a large colony of female rhesus monkeys. The monkeys are housed in small social groups of about 5. This becomes very important because monkeys will quickly organize themselves into strict social hierarchies, with one being most dominant, one being most subordinate, and the final three ranged in the middle. And there's a simple way to control the hierarchy. Put one new monkey into an established group of four, and that one will usually end up at the low end of the totem pole. This means that you can control the social environment of the monkeys without issues of naturally dominant personalities (you might have been top in the old cage, but not anymore). And it means that you can use these social groups to look at the physical effects of social environment.

In this case, the authors were interested in the immune system, particularly peripheral blood mononuclear cells, which include things like white blood cells. They found a whole host of genes in these cells which varied in their transcription level as a function of social dominance.

Of these genes, the largest group were associated with immune system function. And the gene regulation varied as a function of social dominance, so much so that the authors could predict the rank of the monkeys in 80% of cases by their gene expression profile. And in cases where the social rank of a monkey changed during the experiment, the gene expression also changed, and again was predictive of the monkey's social rank.

These changes in gene expression also went along with differences in the types of immune cells found in the monkeys' bloodstreams (and which accounted for some of the differences in gene expression in the samples). Lower ranked monkeys showed lower levels of a type of immune cells called the CD8+ T cell, otherwise known as the killer T cells you might remember from your high school biology class. These are an important part of the immune response that can kill cells that have been infected with viruses, which gives a nice link between the social rank of the monkeys and the differences in illness susceptibility seen in previous studies in monkey and humans.

But changes in gene expression patterns are more the result of the social environment. They are not really the underlying mechanism. What is it that is changing in these cells which in turn changes the gene expression pattern? In this case, the appears to be gene methylation. Gene methylation (a type of epigenetic modifiction which is getting a lot of press these days) is when a methyl group is attached to a cytosine (part of the A, C, T, G of DNA) of a DNA strand. In most cases, this results in a decrease in the gene expression for that gene. Methylation is a changable process, and genes can be methylated or un-methylated in response to changes in the environment or physiology. In this case, they found different patterns of DNA methylation in high and low ranking monkeys, suggesting that changes in DNA methylation are responsible for the changes in gene expression, and thus immune function, that are found in high and low ranking animals.

These changes associated with gene expression and methylation mean that it's the social dominance that changes the gene expression, rather than immune system gene expression playing a role in social dominance. Being at the bottom of the social totem pole really IS bad for your immune system. It will be interesting to see what role the stress of being the social subordinate (and it is a very stressful position, as seen in previous studies) plays in these changes in methylation and gene expression. And it also suggests that relieving social stress could really be good for your health, or at least, be good for your immune-related gene expression.

Tung, J., Barreiro, L., Johnson, Z., Hansen, K., Michopoulos, V., Toufexis, D., Michelini, K., Wilson, M., & Gilad, Y. (2012). Social environment is associated with gene regulatory variation in the rhesus macaque immune system Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1202734109

The views expressed are those of the author and are not necessarily those of Scientific American.

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