History Connections: The Epigenetics Revolution, Part 2

In the May 2011 issue of Canadian Chiropractor magazine, we looked at
the new science of epigenetics and its impact on traditional concepts of
heredity, disease and longevity. Epigenetics has profound implications
on three core areas of chiropractic practice: mechanobiology, pain and
wellness.

In the May 2011 issue of Canadian Chiropractor magazine, we looked at the new science of epigenetics and its impact on traditional concepts of heredity, disease and longevity. Epigenetics has profound implications on three core areas of chiropractic practice: mechanobiology, pain and wellness. In Part 2, we take a closer look at its significance to chiropractic.

MECHANOBIOLOGY
Dr. Marion McGregor, director of Year II Education at the Canadian Memorial Chiropractic College (CMCC), explains that mechanobiology is an emerging field of study that focuses on the way physical forces are transmitted through the tissues to promote changes in metabolic kinetics of cells or tissues, thereby contributing to organism development, physiology and disease. When considering the mechanisms of action of such stimuli at the cellular level, the science is referred to as mechanotransduction.

The role of external and internal forces on cell, tissue and system behaviour is now receiving increasing attention because of a heightened awareness of the simple premise that “all tissues and cells are able to sense their mechanical environment and respond to it.”¹ Much of what chiropractors do relates to the musculoskeletal system and pain, and applying forces to a system is precisely how they do it.

“The dominant business of chiropractic,” Dr. McGregor observes, “involves imparting a force of some kind into the body. As soon as you do that, you are in the realm of mechanobiology. We absolutely know and understand that if you apply a force to a cell, it sets off a range of intracellular events. Such events may lead to clinical change. When we see clinical results that we can’t explain, you begin to wonder if the mechanism of action can be considered from the perspective of mechanobiology. What may have been observed in practice as a unique and odd event that we didn’t anticipate from a physiological point of view – but that seemed to have had its origin in the force that was applied into the system – may be better understood as a chemical chain of events. Although in its bare infancy, mechanotransduction offers a means to begin to map those interactions.”

Dr. McGregor notes that even though they are continually applying force through tissues and cells, chiropractors do not fully know how manipulation works. To remedy this gap in knowledge, the profession must endeavour to examine what actually takes place. Research in basic sciences is advancing and may facilitate our eventual understanding. “One of the strong areas of research is in bone development,” she observes, “whereby researchers at the University of Delaware, for example, have attempted to understand the relationship between mechanical stimulation of osteoblasts, osteoblastic activity and mechanosensitivity.

Such findings may help illuminate the means by which the mechanical stimuli that chiropractors routinely impart to the musculoskeletal system have their observed effects. Hopefully future research by our profession will consider the mechanisms of action described by the basic researchers working in this arena.”

The relationship of epigenetics to mechanobiology can be seen, for example, in the development of sesamoid bones, which Sarin and colleagues expressed as “mediated epigenetically by local mechanical forces.”² The 2011 Congress on Computational Bioengineering has a session dedicated to mechanobiology and recent developments in epigenetics.

“Influences exist at the environmental level, within the individual, and within the cell at the point of the signaling pathways,” continues Dr. McGregor. “Many factors interact in a very complex way that we do not understand. As chiropractors we are a part of interacting with those systems and right now we are beginning to say we need to pay attention to how we impact those systems. We’ve never done that before. Everything we’ve done has been on either a large environmental level or a discrete individual level; we have not spent the time going down to the cellular level to determine what is driving the system. The individual’s epigenetic response to a mechanical stimulus is the new frontier for us.”

THE PAIN MODEL
Our modern understanding of pain includes recognition of changes that occur in an epigenetic fashion. Underlying that is a deeper mechanism that could be called “activity-dependant.” According to CMCC professor Dr. Howard Vernon, the way cells function changes them, and part of that change is at the level of genetic expression. Different proteins are produced as a result of the demands placed on particular systems.
“All muscles have an initial genetic profile placing them in a particular type of muscle fibre group,” he notes. “Postural muscles, for example, have an anaerobically-based genetic profile that enables them to perform longstanding, static activities with very little oxygen. They have chemistry and a structure that serves them to remain ‘on’ for great lengths of time. That’s what posture is all about.

“When we perform certain types of activities with these muscles, however, we can alter that profile so that when we look at the proteins and cell structure again it has changed to the kind of muscle that is used for fast-paced activities such as running. The muscles of our limbs are based on aerobic activity. They need oxygen so there’s a different chemistry profile, energy use and cell structure. If we were to exercise the postural muscles in a way that requires them to work in an alternating ‘on-off’, quick bursting kind of fashion we will see a transformation to the other type of muscle. Changes of this kind are not imposed on the cell by some external source – they emerge out of new and activity-dependant genetic expression that produces these proteins that change the nature of the cell. These are phenotypic changes of the cell at a very basic level.”

Dr. Vernon suggests that we are now learning more about how this occurs and, in the process, we have also learned more about pain. Pain, in a sense, becomes a laboratory for that very basic process. Once we understand the mechanisms of pain at the cellular and intra-cellular pathway levels, we can begin to see how the processes behind phenotypic cellular changes occur. Pain becomes useful to those who want to study this phenomenon and, conversely, we now understand that the changes in function and phenotypic expression are part of the mechanism of how pain works – particularly how it becomes chronic.

“The major issue of pain that references epigenetics,” Dr. Vernon states, “has to do with how it is that when pain persists, things start changing. Epigenetic processes are at play to produce changes in cells such that they begin to behave differently – like staying “on” all the time instead of turning “off.” This can lead to pain for a longer period than anticipated, creating the clinical situations experienced by many people.

“Because the story of epigenesis has an impact on chronic pain, those who deal with pain should be made aware that pain is an adapting type of situation. It is not just an “on-off” state. When we look at people who experience pain for a longer period of time, it’s not just that the injury is still there. The nervous system is plastic. Pain has a profound effect on the way the nervous system functions and changes, and it is the alterations in the nervous system – that is, changes in the way the programming inside us works – that are the problem. It’s a software issue that comes about in large part because of these epigenetic changes.

“We have not been able to observe this clinically,” continues Dr. Vernon. “This is work we’re doing in animals where we can study cellular change but we have no way to test and prove it in humans. When a patient asks me ‘Why am I still in pain?’ we have to understand that people’s bodies change in response to chronic pain and it is these changes that are the basis for the next stages in the progression of their condition. This is where pain and epigenesis come full circle.”

Epigenetics is the influence of the environment on the expression of genes – specifically, the expression of the genome to produce different phenotypes. Dr. Vernon believes “we do not have a single pathway from our inherited genome to some deterministic outcome the moment we are conceived. The environment has a strong influence on this genetic expression and the subsequent manifestations of our physiology and our mode of life. Pain is part of that continuum.”

WELLNESS
Chiropractors provide holistic, wellness care to a greater or lesser extent, depending on the nature of their practice. In a nutshell, the same advice about sound, health-promoting life choices that applies to the individual today would also apply in the context of our current understanding of epigenetics. What has changed is our awareness that deleterious life choices can have a profound effect not only us, but also on the health and longevity of future generations.

Epigenetic research suggests that the impact on longevity witnessed in the Norrbotten descendants was caused by changes to epigenetic markers on their DNA. According to a consortium of European epigenetic researchers, one of the most important diet-related epigenetic changes is methylation.³ DNA methylation, along with modifications of DNA-packaging histone proteins, is one of the major epigenetic mechanisms that cells use to control gene expression and is a common signalling tool that cells use to lock genes in the “off” position. It is an important component in numerous cellular processes, including embryonic development and preservation of chromosome stability. Given the critical processes in which methylation plays a part, it is not surprising that errors in methylation have been linked to a variety of catastrophic human diseases such as cancer, lupus, muscular dystrophy, and a spectrum of birth defects.⁴ DNA methylation has also attracted the attention of behavioural epigeneticists who, in addition to short- and long-term memory, study an array of psychological issues including children’s aggression, drug addiction, depression and suicide.⁵

“In order to faithfully maintain the correct patterns of methylation through cell division, new methyl groups are stuck onto freshly-copied DNA. This requires a constant supply of new methyl groups, which can be provided directly from our food, including the trio of molecules methionine, betaine and choline.”⁶ We can also make methyl groups from chemicals such as folic acid.

Other nutrients, such as vitamin B12 and zinc, are involved in transporting methyl groups and attaching them to DNA, and deficiencies in these essential molecules can have effects on levels of DNA methylation in the body. Because our grandchildren are what we eat, adequate levels of these nutrients are essential to set up the correct patterns of methylation not only in our own bodies but in our offspring as well, and these patterns, in the form of epigenetic tags, are also passed on to the next generation.

DARWIN’S DNA AND THE EPIGENETICS REVOLUTION
Epigenetics introduces a new dimension to the interaction between us and the environment. It can allow us to make a range of individual, personalized responses to external stimuli irrespective of our genetic programming, and some of these adaptations may be passed to future generations epigenetically.

This astonishing and, until recently, unsuspected flexibility in our ability to shape physiological characteristics in ourselves and our offspring comes with both hope and a warning. DNA is not your destiny. Not all characteristics are hard-wired into our genetic makeup. Epigenetics shows us that the plasticity inherent in our phenotypes allows us to adapt to changing environmental conditions more quickly, and to an unimagined degree, and that adaptive changes in human physiology are not limited to Darwin’s classic model of natural selection and mutation over many generations. Until we better understand the strange witches’ brew of nature and nurture that makes us who we are, it may be well to bear in mind that beneficial lifestyle choices today have not only the potential to improve our health outcomes but may have an impact on the health outcomes in our descendants as well. On the other hand, ill-considered lifestyle choices, like those of the villagers of Norrbotten, may radically alter longevity and health outcomes for generations to come.

As one Norrbotten researcher observed, “We are all guardians of our genome.”⁸

REFERENCES

1. Triano, JJ. The science and clinical application of manual therapy. Edinburgh: Churchill Livingstone; 2011. Chapter 6, Survey of mechanotransduction disorders: p.105.
2. Sarin VK, Erikson GM, Giori NJ, Bergman AG, Carter DR. Coincident development of sesamoid bones and clues to their evolution, The Anatomical Record, 1999; 257(5): 174-180.
3. Epigenome Network of Excellence, http://epigenome.eu/en/2,48,875
4. Phillips, T. The role of methylation in gene expression. Nature Education, 2008; 1(1).
5. Berreby, D. Environmental Impact: Research in behavioral epigenetics is seeking evidence that links experience to biochemistry to gene expression and back out again. The Scientist, March, 2011; 25(3): 40.
6. Epigenome Network of Excellence, http://epigenome.eu/en/2,48,872
7. Epigenome Network of Excellence, http://epigenome.eu/en/2,48,875
8. The Ghost in Your Genes, BBC Science and Nature, http://www.bbc.co.uk/sn/tvradio/programmes/horizon/ghostgenes.shtml

Steve Zoltai is the collections development librarian and archivist
for CMCC and is a member of the Canadian Chiropractic Historical
Association. He was previously the assistant executive director of the
Health Sciences Information Consortium of Toronto. He has worked for
several public and private libraries and with the University of Toronto
Archives. Steve comes by his interest in things historical honestly – he
worked as a field archeologist for the Province of Manitoba. He can be
contacted at szoltai@cmcc.ca.