Networks of Genes Respond to Social Experiences

PIt is extremely surprising how networks of hundreds of genes respond immediately to human interactions and thoughts—despite the fact that actions of humans are eight orders of magnitude larger than molecular genetic events. But, it is, perhaps, more remarkable that networks of genes respond rapidly to social experiences. Previous posts have discussed the immediate neuroplasticity that occurs in widespread circuits with very complex detailed genetic production of new proteins, including motors, tubules, receptors, and neurotransmitters. The immune system does the same with cytokines, receptors, and antibodies. Now, it has become clear that meditation, tai chi, social interactions, abuse, charitable actions all affect very specific networks of genes in the nervous system and the immune system.

But, how can a network of genes deep inside the nucleus respond to events as if it is a brain? In fact, we don’t know how brains respond in such a detailed genetic manner, but having the genes of individual cells, deep in the nucleus respond as if it is a brain is truly remarkable. When networks of genes respond to social experience, it is further evidence of mind interacting at all levels at once, including the 12 orders of magnitude from world civilizations, to molecules in the nucleus.

White_Matter_Connections_Obtained_with_MRI_TractographyPrevious posts show how dramatic changes occur in neuronal genes instantly with thought or behavior with neuroplasticity.  Recently, it was shown that exercise effects 10,000 genes, that insulin effects 7 thousand genes in the cell. Meditation, a conscious mental activity, causes changes in thousands of genes in immune cells.

Human action or thought alters genes by expressing certain ones and suppressing others. There appears to be a dimmer switch on each gene that can increase or decrease activity based upon many levels of regulation (methylation of DNA, methylation of histones, regulatory molecules such as promoters and inhibitors). The process is even more complex through alternative RNA editing of the code. These alterations of RNA through cells’ self editing of messenger RNA create very particular shaped proteins to express a particular thought, feeling, or activity.

Bees In New Environment Modifies Large Network of Genes 

Bee and flowerChanging environments dramatically alters genes, almost immediately. In a study, infant bees were taken from two very different colonies—one group from the mild mannered European bees and another from the very aggressive African bees. They were then switched and put in the opposite tribe’s hive. Growing up in the new hives, the African bees became calm and the European bees became aggressive.

Remarkably, as the bees changed in their new homes, large networks of genes were completely altered. Being in the new environment completely remapped the networks of genes in a short time. As the bees entirely changed their personality and behavior, they looked more and more like the bees in the new hive. And their genes’ activity looked like them, also.

Every Cell Has All the Genes

stem_cell.358142642Every cell has all genes available; so, the difference between stem cells, kidney cells and brain cells is  expression of sets of genes in different patterns. Changes in genetic expression occur in specially timed sequences in the fetus, childhood, adolescence and adulthood.

Gene changes, also, occur based on environment, both long term and short term. Most remarkably, they change based upon behavior and thought. Genes switch on to fight different infections, or can become unhinged and develop cancer. If too many genes change, the entire nature of the cell could be different; the entire nature of an organism could be different.

Danger Signals

Ahaetulla_threatWith signals of danger, such as sounds or smells, large numbers of genes become activated at the same time in large networks. The greater the aggression, the greater are the genetic changes. The genes and behavior change together. Hearing a pleasant signal or a danger signal immediately activates and dampens completely different genetic networks. In animal research these gene changes occurred within minutes.

Observing change in gene networks revealed critical specific regulatory genes that are responsible for altering a large group of other genes. These “immediate early genes” were previously known to occur in immunity and in eating. Recently, these same regulatory genes have been found to change entire networks of genes based upon social and behavior experiences.

In one experiment, a dominant fish was removed from a tank and almost immediately the second ranked fish had massive changes in large networks of genes within several hours. In fact, this fish grew 20% in several hours.

Epigenetic Changes

Microsoft PowerPoint - Presentation1 (3) [Read-Only]Previous posts have described the dramatic findings of ENCODE (Encyclopedia of DNA Elements research consortium of 160 international research centers), which showed that millions of regulatory RNA particles are produced by DNA as well as proteins. These regulatory particles, (including microRNA, long and short non coding RNA, and protein promoters) have dramatic effects on DNA. (See posts on ENCODE and RNA regulatory particles.)

Another type of DNA regulation is epigenetic marking, including methylation of DNA and histones.

Epigenetic markings effect changes that can be inherited for generations. Mothers exposed to famine had altered genes affecting their health. The alterations, also, affected their children and grandchildren. Mothering and caring behavior can change the epigenetic markings and create different genetic network expressions.

Stress related genes alter methylation of DNA, but long-term behavioral changes occur because of neural circuits. How does methylation translate into neural circuits?

  • mouse-and-babiesMothering sets up a calibration in the child as to how the brain responds to stress. More methyl groups with less nurturing mothers produce less receptors. Altered hormones affect the baby’s future behavior. Mice raised in groups are better socially and have more receptors. Stress activates more methylation of the gene of BDNF, which produces less BDNF affecting brain cells and neuroplasticity.
  • Addiction is another example. It produced more acetylation of histones and decreased methylation of histones in the specific region of reward in the brain, nucleus accumbens, decreasing dendritic spines. More methylation also increased animals desire for cocaine.
  • Another example is demonstrated in autopsies of suicide victims. They were abused as children and upon autopsy found to have more methyl groups on the cortisol gene. 

What Creates Rapid Changes in Gene Networks

Antibodies-attacking-a-virusPerhaps, the most remarkable genetic system is the immune system—the largest genetic network in human beings. The immune system edits its own DNA to create enormous numbers of different shapes that will eventually match any shape that the extremely rapidly evolving bacteria and viruses can produce. These wildly diverse antibodies created by cellular self editing not only create a lock and key match with part of almost any protein nature throws at them, but also, man made new chemicals in food and the environment.

Social Experiences Have Powerful Effects on Genes

The environment influences the organism as new cells are built each day. Billions of new blood cells, skin cells, and mucosal cells are made each day and these cells’ behavior are triggered by changing DNA networks in response to our experiences, and the chemical environment we are passing through. In the brain many new glial cells and a small number of neurons are, also, made each day. 

FEATURE MAN iStock_000013969262XSmallSocial connectivity has powerful effects on genes. The gene networks of social experience are consistent through many animals.

  • Studies show human loneliness predicted less immune response to microbes. HIV patients who were hiding their sexual orientation had greater amount of cancers and infections.
  • People with more friends have fewer colds.
  • Stress has major effects on the immune system. Monkeys with SIV (simian HIV) who were moved constantly into new social groups became ill more frequently. The immune system did not respond to the stress signal.
  • Another study showed that lonely and engaged people had dramatic differences in hundreds their genes.

The immune system sends both inflammatory and anti-inflammatory responses at the same time to make sure that the inflammation doesn’t get out of control. In lonely people, the 130 genes that keep inflammation in check were not functioning, but the 80 causing inflammation were very active. These imbalances of the immune functioning operate also in people in poverty as well as people with cancer, depression, and those caring for the ill. 

isolationSocial isolation is much more devastating than stress—the best-known disease risk factor. Isolated poor people do very poorly, while high pressure stressed people in good networks do well. The diseases of isolation are obesity, diabetes, hypertension, coronary heart disease, and strokes. 

  • Poor children showed more active inflammatory genes. Ambiguous social situations are threatening and affect immune genes. If the social scene is frightening then it affected gene networks, not just poverty.
  • In abused children where negative gene changes occurred, those children who had one adult support experience monthly did not have this gene effect. The lack of connection was more damaging than the abuse. Isolation was the most damaging.
  • With ovarian cancer 220 genes were activated for those women with less support and depression.

Genes Change With Changes of Behavior

People can dramatically change which gene networks are activated and suppressed by their behavior. Perception and attitude have the strongest effects. Being able to adapt and adjust attitudes are very important for immunological health. In fact, studies show that subjective experience is the most important aspect of the environment. 

Feeling close to others (even if they are not physically present for isolated or imprisoned people) will protect the body with positive gene changes. Experience is what we take from the environment. Perhaps, this is one reason a spiritual teacher provides such support. The fact that subjective perception strongly affects the immune system is evidence of the power of the mind. 

communityservicePrevious posts described the details of dramatic immune changes with both meditation and charitable service. (See post Meditation Update for more details). Both of these are conscious behaviors.

With pleasure from charitable community service (not pleasure from other self oriented activities) there is a decrease in the gene activity of pro-inflammatory cytokines such as IL1B, IL6, IL8, and TNF. There was increased expression of genes involved in type I IFN antiviral responses including IFI-, OAS-, and MX- family genes. There was also increased IgG1 antibody synthesis.

Istock FEATURE MEDITATION 2013 DidjMeditation-WarpWith meditation, yoga, Tai Chi and other practices many positive immune changes occur. These include decreased immune inflammatory factors interleukin 6, and NF-KappaB, and an increase in the important antiviral factor IRF1. Other studies showed decreased inflammation with local skin burns, fewer colds and decreased stress hormones.

Long term meditators and novices both showed epigenetic gene expression changes related to increased mitochondrial resilience. The genes that changed related to very significant functions including energy metabolism, mitochondrial function, insulin secretion, telomere maintenance and decrease in inflammation and oxidative stress responses. The meditators had less respiratory infections. Meditating dementia caregivers had 68 gene changes related to decreased inflammation.

This demonstrates that conscious mental activities and behaviors can have major effects on our immune systems. 

Genes and Social Behavior

The social world outside determines what the genes do within the nucleus of the cell.

Social experiences can impact genes in many different ways. Genes have regions that if triggered by stress will release cortisol. Another region will stimulate norepinephrine and dopamine to trigger the body’s fight and flight response in cells throughout many organs. These two triggers exist in various places in the genes and can create a variety of different proteins.

The brain responds to social situations by stimulating hormones, immune cytokines and neurotransmitters to produce transcription factors that will alter gene networks. The hypothalamic-pituitary-adrenal (HPA) and sympathetic systems are  powerful gene activators. Signaling molecules trigger receptors on the cell surface, then a cascade to the nucleus stimulates the genes. Different transcription factors produce different pathways, such as Nf-kB and CREB.

These different gene networks form a wiring diagram of genetic response. The entire normal brain response to ordinary signals can be altered in this process. 

CSM-Man-For-PPT-e1337893133731In the isolation experience, for example, the factor NF-kappaB that drives inflammation becomes very important in determining the specific response of signals. Cortisol, which normally inhibits NF-kB, doesn’t do this under stress and isolation. It does the opposite. Therefore, the response to the entire HPA signaling is altered.

The brain is signaling to decrease inflammation, but the receptors and the cascades ignore this. Isolation and social loss both disconnect a critical normal physiological mechanism. This is just one example of complex genetic mechanisms that respond to abuse, isolation, and other social circumstances.

The response to social situations, also, alters RNA editing and transcription, changing the entire network of genetic signals, just as if it were a brain with a new circuit. Chronic stress increases a factor, NGF, and this increases sympathetic nerves in the lymph nodes (the brain circuits of the immune system). As this nerve changes in the lymph node, the response to a virus is decreased. The entire relationship between the immune and nervous system has shifted. Later, interferon genes are inhibited in this process, which changes future responses as well.

In this way an experience creates a new circuit in the immune/nervous genetic systems, which can last for years. 

Subjective Mind Changes Genes – Not Just External Situations

The place of the mind becomes clearer in this analysis. The psychological perceptions and experiences become the way genetic circuits are modeled—by the perceptions of external events, not the events themselves. It is the subjective mental awareness of these events that determines the genetic rewiring.

Events can alter extensive wiring diagrams through specific genetic pathways. Mind changes how the brain uses its circuits. And mind changes the ways that genetic circuits in cells are altered. In brains measuring MRI doesn’t tell mechanisms or cause and effect. In the same way, measuring genetic circuits doesn’t tell cause and effect.

Networks of Genes Respond to Social Experiences

Where is the Brain in the Gene?

It is quite remarkable that brains are able to respond to situations and mental events with almost instantaneous changes in wide ranging circuits, including many different very complex molecular changes in different neurons and astrocytes. A second later, a different circuit of neurons, some including the same neurons and some not, suddenly respond to the next event. 

Brain of genesBut, it is far more extraordinary to consider that social situations almost instantly trigger networks of genes, deep inside the cell. It appears that there are specific genetic hubs that can suddenly trigger thousands of genes in different ways–stimulating some and inhibiting others. These events trigger far reaching networks of cells, all at once, in the immune system, the hormonal systems, bodily organs and the nervous system. What is the brain deep inside the cell’s nucleus where networks of genes respond to social situations?

It is subjective mind and perception that changes genes, not just external situations. This is further evidence of mind affecting a large number of orders of magnitude simultaneously. 

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  • Matthew Rehrl MD

    There is also a nice recent study showing longer telomere length in a subset of women meditators; Although not necessarily showing causality, it does suggest that meditation may make changes at the chromosomal level.

    ( Ref : http://www.ncbi.nlm.nih.gov/pubmed/23602876 )

    Thanks for your excellent posts.