A company creates a very successful name-branded product, and next thing you know, that name brand has become the name of the product itself. Examples are: Kleenex (facial tissue), Crock-Pot (slow cooker), Onesies (infant body wear), Bubble Wrap (air insulating wrap), and Jet Ski (personal watercraft). Jacuzzi is a brand of hot tub. Guide dogs could only be legitimately called Seeing Eye Dogs if trained by Seeing Eye of Morristown New Jersey, but we call all guide dogs as seeing eye dogs — the name stuck.
In popular medicine, genetics became the catch-all term for cell behavior — cells always did what their genes told them to do. But then, with our ability to decode DNA, researchers learned that genes can exist but not be expressed — in fact, the majority of genes are inactive at any particular time. So the term “epigenetics”, once an obscure term, has become the new determining factor in cell behavior. Almost like a fad, the term is taking over and many medical articles now refer to epigenetic causes for cancer and disease. But neither genetics nor epigenetics are causes. Genes are reference libraries, and epigenetics are reactions — neither refer to actual cell behavior.
Signaling could legitimately take over as the name brand for cell behavior, although the name isn’t likely to do so as it isn’t very “catchy.” But to understand why a cell does what it does, you have to look at cell signaling — not genetics or even epigenetics.
Epigenetics do not have a mind of their own
Genetics are regulated by epigenetics, which activates or inactivates certain genes. Epigenetics, in turn, is a servant, doing what it is told to do by signals the cell picks up. Cells interpret their environment through signals they are able to receive — not all cells can receive all signals. The cell receptors are the gateway for receiving signals through proteins which match the “code” for the receptor.
Published in IUBMB Life (the journal of the International Union of Biochemistry and Molecular Biology), researchers from the Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Ciudad Universitaria, México made this statement: “…analyzing the relationship between cell signaling and epigenetics will be a huge area for future development that will help us understand the complex process by which a cell is able to induce transcriptional changes in response to external and internal signals.” Their research shows that not only are the factors of methylation (marking DNA segments to turn them off) and histone function (proteins that wrap the DNA strand more or less tightly to promote or retard transcriptions of specific portions of DNA) key to epigenetic function, but also ATP-dependent chromatin remodelers (which can mobilize histones) and long noncoding RNAs (which do not code proteins but can regulate gene expression) are also key in epigenetic expression. In other words, there are many factors which contribute to whether a gene, normal or mutated, ever gets expressed.
Why does your body have such complexity? Why are there so many genetic combinations possible, and so many ways to control expression of those genetics? The simple answer is: we are designed to handle and even thrive in a highly diverse and unpredictable environment. Our genes have built a vast library of instructions for most any situation, and our epigenetics pick and choose which instructions to follow to best handle what our bodies are sensing from the environment. This process is largely trial and error; in other words, your cells are constantly looking through your genetic library to find the best instructions in the current situation. So what happens when a mutation causes some instruction to go wrong? Then the result is not what your body needs in its current environment, the trial and error process is “error”, and your body, if healthy, will tell the cell to die, or will kill it, because it is not performing according to its signaling. So incorrect instructions from mutated genes generally get rejected as unhelpful and many times causes that cell to just die prematurely so it will not keep communicating misinformation. When mutations are acted upon, it is because the cell perceives the instructions to improve its function, such growing cells faster as when dealing with a harsh, toxic environment. This is when mutations become dangerous – the body believes the mutation furthers its survival in its toxic environment, and this is when a cancer cell is born.
Mutations usually harm the genetic code. They don’t add some new function, but they are good at damaging current functions, such as cell reproduction regulation. Consider what random garbage does to any form of information. If you drop some ink on a page of a book, is it now more readable? Does some new aspect of the plot appear due to the ink blot’s damage to some of the words? Mutations are garbage thrown into an information library. If cells act upon the garbage they are going to stimulate a response to the garbage and that response is almost always “grow more cells.”
The lab dilemma
But what happens if it’s not the information library (genetics), but the gene expression mechanism (epigenetics) which gets hit with a mutation? Technically, that can’t happen to any significant degree, because the gene expression mechanism is made of up proteins, which are encoded from genes. A mutated protein won’t do much damage, but a mutated gene can encode a number of proteins, and if these proteins are part of the epigenetic control process, they can have significant impact. Published in Nature, researchers at the Perelman School of Medicine of the University of Pennsylvania took cell lines from active patient tumors that had mutations in the TP53 gene, which encodes the protein p53, responsible for cell repair and destroying cells which have severe DNA damage. The cell lines were now separated from the patients and grown in a laboratory. In that environment, they found that the mutated p53 protein that was being produced was causing methylation and acetylation of DNA, which means it was performing an epigenetic type of control of genetic expression which was aiding tumor growth.
So, did they just show that mutations can hijack epigenetics? In the laboratory test conditions, that was the result that they observed. So obviously it is possible for mutations to, under certain circumstances, influence epigenetic responses. But in the process of simplifying their experiment by growing the cells in the lab, they were also cutting out many important variables that affect epigenetic reactions; namely, the vast array of cellular signals that would be occurring in the human body.
Cellular signals rule
Signaling is an extremely rapid and dynamic process. Your cells are receiving and sending millions of messages at this moment. This poses a problem for laboratory settings running epigenetic experiments: the system is simply too complex to replicate in a lab. Scientific experiments require a reduction of the variables that could impact the experiment to a few so that the experiment does not become too massive to handle. The only valid laboratory for an experiment into epigenetics is an entire living body — anything simpler omits too many variables that our cells deal with in real life. The moment you lab-grow tissue, you’ve created a situation where the cellular signaling is vastly different than what it would receive in a living, active body. The results may offer clues as to how cells might respond in the greater, more complex environment, but they are far from conclusive, particularly when it comes to epigenetic reactions.
There is a huge difference between cells integrated into a complete living body and cells grown in a lab. Your cells are meant to work together as a community. To do so, they have to talk to each other – a lot. There are many epigenetic mechanisms meant to enable a very flexible response to differing environmental conditions. You may have some genetic mutations that are right now influencing your genetic expression. But they are not the whole story. The cellular discussions that are happening in your body are affecting many epigenetic reactions, more so than a damaged genetic instruction. Therefore, even cancerous cells can, with the right signals, change their behavior – this won’t be seen in any lab.
Let’s take diet. Published in Epigenomics, scientists at the University of Alabama at Birmingham reviewed various dietary studies and their impact on cancer. They stated, “Importantly, emerging evidence strongly suggests that consumption of dietary agents can alter normal epigenetic states as well as reverse abnormal gene activation or silencing.” They review various phytochemicals that show evidence of affecting epigenetic processes, including reactivation of tumor suppression genes. What they are seeing is that the nutrition and phytochemicals are providing a favorable environment for normal, healthy gene expression instead of rogue cancerous development. The cells, doing the best they can in their situation, respond according to their environment.
Diet is only one factor. Exercise, rest, hydration, and stress reduction all work to present your cells with a healthy environment, promoting epigenetic decisions towards normal, healthy behavior. Your whole body is a diverse community of cells with different functions but all tied together by communication. Your body tells its cells how to behave, and there are many ways it can adjust even with some messed up genes. Its toolkit is vast, and it chooses a variety of epigenetic tools to keep you healthy. The design built into your body can take challenges and overcome them because it has such a massive array of tools to work with. Your health is not branded by genetics, or even epigenetics, regardless of attempts of some laboratory research to oversimplify cellular function. Health stems from proper cell signaling, which in turn stems from a good environment. Epigenetics is the servant of cell signaling, not the master. It will do what the community tells it to do.
Dr. Nemec’s Review
Are you a good talker or a good listener? Your cells are good talkers after they have been good listeners and they are listening to the signals coming from the environment you have made with your thoughts, actions, diet, and lifestyle. So it comes down to listening to the environmental cues that are coming in from the way you think and live. What are those signals if you eat inflammatory standard American food choices? They are ones of stress and hyperactivity to the cells because that is what inflammation does. When we look at diet we see various signals being relayed to your cells and those cells listen and react to those signals. So let say that you are eating meat and a lot of simple refined carbs and starches. These foods are stimulating to the cells and it gets them reacting in a hyperfunction mode. If your cells are constantly being stimulated this way then they will produce an epigenetic marker or tag to tell the gene to make cells quicker because they are burning out faster with this diet. This tag sticks and now the new gene output is one of growth because you made a pattern of stress, burnout and mutation at the cellular level that needed to alter the genetic code to take care of this long term. From these stressful signals of diet the epigenetic markers were applied to affect cell growth longer term. This is how cancer develops. The cells of the body can take all kinds of stressors but if you keep stressing them they will change their genes response epigenetically to reflect a whole new permanent environment. How could you have stopped this? Do not eat food that stresses your cells. Which foods are helpful? They ones you were designed to eat: living and raw plants, greens, sprouts, vegetables, low glycemic index fruits. These foods make the right signals to the cells so they do not have to overwork, die prematurely or cause harmful mutations to occur.
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