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BLOG: October 2007

Epigenetic therapy

Can what and how your grandma ate before you were even born make you sick? According to the new kid on the block, epigenetic medicine, it can. Not only diet, but pretty much any significant prolonged exposure to challenging environmental, physiological and psychological factors can cause inheritable epigenetic changes in your basic body functions.

Youngsters are more vulnerable to the direct damage, and the most vulnerable are babies in mother's womb (due to mother's exposures). On the other hand, older people are more prone to epigenetic damage resulting from accumulated abnormalities of many cellular divisions, the older they get, the more so. The rest of population is somewhere in between.

And, as any other, epigenetic vulnerability is likely to vary significantly from one individual to another. But, what does "epigenetic" actually mean?

Epigenetic mechanism is how the body regulates its genes. Every single cell in your body has identical genetic (DNA) material. Yet, cellular forms arising around this genetic code vary widely, from one tissue to another. The body regulates which genes are active, and which are not at every location in the body, within every single body cell. It does it by selectively switching off - or silencing - genes that are not needed, either by making them inaccessible to so called transcription enzymes by a selective pattern of direct DNA methylation and/or re-structuring special proteins - histones - wrapped around the DNA, or by disabling gene's RNA from replicating into body proteins.

Genes themselves form the genom (genetic code); substances and mechanism turning specific genes on and off constitute the epigenom.

Epigenom can be altered by foreign materials present in the cell, that have the ability to influence the process of gene expression. These non-genetic agents can be either a product of body's own metabolic process or very specific xenobiotic substances (good example being epigenetic drugs themselves).

And there is evidence that the external factors we are exposed to - lack of excess of food, prolonged stress, challenging physical exposures, etc. - can modify gene expression, either as a result of genetic function being affected by altered cell division rate, cellular repair process, or as a result of the body trying to adapt.

Needless to say, the very process of regulating gene activity - or gene expression - is directly or indirectly dependant on the specific epigenom controlling the genes. So it is also possible that improper function of the genes involved in this regulatory action causes improper activation/deactivation of other genes. 

This is when epigenetic changes become a permanent mode of function; in other words,

they become inheritable.

While the rest of your genom is still intact, some genes that should be on go off, and the other way around. It can negatively affect any body function, and cause any disease. While the consequences in this respect are very similar to those of having those specific genes damaged, genetic malfunction caused by faulty epigenom is easier to correct, than to restore damaged gene.

Obviously, the fact that our gene expression mechanism can be affected by external factors has its good side. It makes possible influencing it with pharmacological agents, which brings us to epigenetic medicine. From its beginnings in the early 1980s, it was mainly limited to treating cancers, and in particular blood-related cancers, like MDS (Myelodysplastic Syndrome) or leukemias. However, it shows results with a number of other cancer forms, from melanomas to colon cancer.

In addition, epigenetic therapy is routinely used in the treatment of bipolar disorder (with Valproic acid), which indicates that epigenom - as it is to expect - can affect other aspects of human health, which should also benefit from epigenetic therapy in the future. This, however, will require acquiring new knowledge in both, mechanism of action and proper application of epigenetic drugs.

Cancer cells, in general, are attracted to these drugs because they divide at much faster pace than normal cells. This effectively concentrates drugs onto them, with normal cells being, in comparison, only mildly affected. With other disease types, where epigenetic damage may be significant factor, but doesn't cause significant acceleration in the pace of cellular division, it is still needed to find a mechanism through which a drug is selectively delivered to the affected genes - something easier said than done.

For purists, epigenetic therapy may still be a part of symptom-treating medicine, in that it uses drugs to influence body processes, instead of helping the body to heal on its own. But as long as it restores proper body function, without significant risks or side effects, does it really matter? One thing is certain: a therapy that works by re-programming abnormal cells is a

giant leap ahead from those that work by killing them, and indiscriminately killing many healthy cells in the process.

What is to remember is that anything causing cellular damage, and thus accelerated cell division as well, not only accelerates ageing, but also increases your risk of epigenetic damage. And that it may affect not only you, but your descendants - and descendants of your descendants.

Some familiar culprits come to mind: poor diet, trans fatty acids, free radicals (excessive sun exposure, smoking), prolonged stress, physical over-exertion, etc.

On the other hand, anything that protects your cells from harm also protects you from epigenetic malfunction: healthful diet, anti-oxidants, anti-inflammatory nutrients like Omega-3 essential fatty acids, positive thoughts, emotions and relaxation, beneficial physical activity. It is all about the very basic rule for preserving health: give to the body what it needs to function properly, and minimize its exposure to harmful elements.