Who is doing gene reprogramming?

When I first learned about computers in 1950, there were probably less than a three dozen people in the world doing computer programming, and I soon joined their ranks.  At that time, to suggest that computer programming would become an occupation involving tens of millions of people would have gotten me labeled as a crazy visionary.  Yesterday I started to wonder about how many people are involved now with genetic reprogramming of body cells.  At first I guessed that the number is anywhere from a few hundred to a few thousand.  Then, later last night, I realized that the number is about 6.8 billion people, the world’s population.  Everybody is constantly involved in reprogramming their own genes. 

Gene reprogramming can involve two quite different things: modifying genes themselves or modifying the epigenomic information that determine what the genes do.  You are born with a set of genes, those same genes are in every cell of your body and, without an extraordinary intervention you will die with the same genes.  It is possible to change some of your genes in some of your cells using sophisticated gene splicing techniques, for example to correct a genetic disease-creating defect.  See the blog post Treating genetic diseases with corrected induced pluripotent stem cells.  However, changing genes is not something that can be done lightly and almost all of us will live our lives out with the same genes we started out with.

Gene reprogramming is mostly about is modification of epigenetic information in the DNA which affects gene expression. After all, the differences between all the different kinds of cells in our body are due to gene expression.  So, “gene reprogramming” usually involves altering epigenomic markers (e.g. DNA methylation, histone acetylation and protein folding) so as to affect gene expression in cells with some objective in mind, such as curing a disease created by a gene polymorphism.   (Why the “re” in reprogramming?  For two reasons: first because computer researchers have pre-empted the term “genetic programming” to describe a fundamentally different algorithmic approach to computing, one that is vaguely based on genetics but not necessarily useful for dealing with what goes on with the DNA in real biological cells.  The other reason is that the cells worked with in reprogramming are already behaving according to some kind of epigenetic program and the objective is to alter that program.)

The big enchilada of genetic reprogramming today is reverting cells to induced pluripotent stem cell (iPSC) status, a matter I have touched on in several previous posts, starting with the post Rebooting cells and longevity. In a matter of only months the tiny initial stream of research in this area is already growing into a river.  New ways are being discovered for turning stem cell genes off and on, for example, ones like manipulation of culture conditions that do not require virus vectors or transgenes(ref).    Here is a recently compiled list of articles related to deliberate cell reprogramming.

But deliberate gene reprogramming using sophisticated laboratory techniques is only a very tiny part of the picture.

Gene reprogramming goes on constantly in the process of aging and is a feature of many disease processes. For example, a 2003 publication, Growth Hormone, Acromegaly, and Heart Failure: The Gene Reprogramming Theory, states “When the myocardium hypertrophies to face an increased mechanical load, extensive gene reprogramming occurs in the cardiomyocytes. Some genes are downregulated, whereas others are upregulated. A distinct feature of this process is the re-emergence of an ensemble of fetal genes that are normally quiescent in the adult myocardium. It was theorized that the hypertrophic cardiomyocytes are sentenced to death, as an inherent consequence of the new gene programme (Katz, 1994)” The 1999 publication Adrenergic induction of bimodal myocardial protection: signal transduction and cardiac gene reprogramming states “The delayed adaptive response is associated with the expression of cardiac genes encoding fetal contractile proteins, and PKC-I may transduce the signal for reprogramming of cardiac gene expression.”  Another article related to gene reprogramming in heart tissues is Myocardial gene reprogramming associated with a cardiac cross-resistant state induced by LPS preconditioning.  Many other studies also relate to gene reprogramming in specific tissues and under particular disease conditions. 

Cancers do masterful jobs of gene reprogramming, sometimes changing the expression of hundreds of different genes. One of the central things most cancers do, for example, is to reprogram so as to inactivate expression of the p53 apoptosis gene.  According to a recently-suggested line of thought “–  cancer could begin when normal cells spontaneously reprogram themselves, for reasons yet unknown, beginning the process that results in a cancerous tumor(ref).”

Gene reprogramming can also occur due to environmental or stress conditions.  In May 2009 it was reported “Breathing polluted air for even a short period of time can cause some genes to undergo reprogramming, which may affect a person’s risk of developing cancer and other diseases, say Italian researchers. — Comparisons of blood DNA samples from healthy workers who were exposed to high levels of airborne particulates at a foundry near Milan revealed that after only three days of exposure, changes occurred in four genes that have been linked to tumor suppression.” – “This finding indicates “that environmental factors need little time to cause gene reprogramming, which is potentially associated with disease outcomes.”

The situation is not always simple.  For example, the reprogramming introduced by stress may be beneficial or harmful dependent on a cell’s capability to mobilize a response to the stress.  See the blog post Stress and Longevity.

What you eat reprograms your genes.  The blog post Recent research on the Mediterranean diet cites research indicating that the cell reprogramming resulting from following this diet results in multiple health and longevity benefits.  Cigarette smoking affects gene reprogramming, probably in several ways(ref) (ref).  So does exercise(ref)(ref). So does taking resveratrol(ref) and taking curcumin(ref)(ref).  In fact all of the dietary supplements in the combined anti-aging supplement firewall induce gene reprogramming to one extent or the other.  So what else can reprogram your genes? Just about everything you experience and do and your emotional and mental states.  See the post Optimism and epigenomic activation.  Simply put, research shows that optimism enhances longevity.  Your mental state can create epigenomic modifications, DNA methylation on your chromosomes and histone acetylation/deacetylation modifications, and therefore alter your gene expression pattern and therefore affect your longevity.The Anti-aging lifestyle Regimen section of my treatise contains numerous “conventional wisdom” suggestions for keeping yourself young.  All of these suggestions – every one of them – is a suggestion about how you can reprogram your genes so as to enhance the prospects for longevity. 

Eating a tripple-cheeseburger whopper with a double order of fries and a giant coke reprograms your genes one way.  Exercising 47 minutes a day (my target) reprograms your genes another way.  You are a gene-reprogrammer!