Dear Mark: Gene Expression

I received tons of emails from last week’s Gene Expression: Location, Location, Location post. Thanks to everybody for their feedback and questions. In the comment section of last week’s post, Ed was interested in other concrete examples of gene expression (the ability of a gene to produce a biologically active protein). In personal emails, others asked for more explanation of the difference between genes and gene expression. Still others wanted to hear more about the interaction between their gene expression and lifestyle choices. Given the range of reader questions this week, I thought I’d reframe this week’s Dear Mark to include more of an overview of this recurring MDA theme. There’s a lot to be said on the subject, and I promise this post won’t be the last word on it. Nonetheless, there’s no time like the present to give a proper introduction and dive right in.

Let me just say that gene expression is one of my favorite areas of interest, and it’s truly at the heart of the Primal Blueprint. In fact, it’s the real beauty of it as well. It confirms that the day-to-day choices we make have incredible impact. And we can influence gene expression to a far greater degree than anyone ever thought possible.

Everyone has the DNA “recipe” to build a human being. The DNA itself is not really so much a “blueprint” (as many people assume) as it is a recipe. As with all recipes, it allows for a little variation to spice things up and even room for improvement. That means that some ingredients can change a little and you still wind up with the intended result. A little more sugar, a little less salt, an added spice, a lower cooking temperature: the end result still resembles the picture in the cookbook.

We often hear about the computer hardware/software analogy. An analogy I like to use is that of a book and its readings. Your genome itself (your DNA) is fixed and can’t be changed. It is the book itself. Once it’s been written (and in this case each of your 60 trillion cells has the exact same copy of your story), you can’t change the words. But a book, even though it’s fixed, can be read differently by different people. (Imagine three different screenwriters taking the same book and coming up with three very different movie versions). The lines themselves are altered in the context of the interpretation.

Similarly, while your genes are “fixed”, the expression of those genes – the amount of proteins they cause to be made, whether or not they are even switched on or off at all – depends on the “environment,” the circumstances surrounding those genes. Diet, exercise, exposure to toxic chemicals (or fresh air), medicines, even the thoughts you think (which generate actual chemical signals) all influence gene expression – positively and/or negatively, depending on the choice. Eat a diet that is high in sugar, and gene expression moves in a direction that produces more insulin, that shuts off insulin receptors, that down-regulates lipase and other enzymes involved in fat-burning, that increases pro-inflammatory cytokines, etc. When you change to a diet low in sugars and rich in healthy fats, those or other genes are directed to reduce inflammatory expression, down-regulate insulin-producing metabolic machinery, up-regulate insulin receptors and rebuild cell membranes to reflect the presence of better building materials (omega 3 fatty acids, etc.). Research in gene expression is exploding right now and is examining both the impact of environmental factors and the promise of epigenetic therapies. The connection between insulin resistance and genetic expression (particularly in relation to exercise) was raised in last week’s comments. Diet and toxin exposure have been shown to influence gene expression in laboratory studies. Here are a few study abstracts to pique your interest: PubMed 1, 2, 3.

The interaction between lifestyle choices and gene expression goes on every second of every day you’re alive. You are literally rebuilding yourself all the time. That’s the message of hope that the Primal Blueprint offers. Even if you have so-called markers for “defective” genes, that doesn’t mean they will be expressed. Gene interaction is such that environmental factors can potentially allow for someone with BRCA1 and BRCA2 (associated with a very high risk for breast cancer) to never get breast cancer if those and related genes are properly controlled through environment. On the other hand, a woman with no risk factors can still get breast cancer if she directs gene expression towards pro-inflammatory pathways, then down-regulates other parts of her immune system.

As I mentioned last week, most of today’s genome investigation centers on SNPs (single nucleotide polymorphisms) that predispose the possessor to a particular condition (cancer, heart disease, obesity, diabetes, arthritis, etc). I’ve always said that a predisposition is not your final destiny. Even aging itself is highly influenced by gene expression over time. In the course of a lifetime, stem cells divide to repair injury (e.g. inflammation). In doing so, the cells are continually aged. The more the cells have to repair, the faster a person ages. This, of course, is a manifestation of gene expression.

The whole idea behind my Primal Blueprint is this: we know that we can influence gene expression, but – more than that – we know HOW to influence it in a direction of health, fitness, productivity, happiness, etc. The “blueprint” is not the DNA but a set of lifestyle and behavioral guidelines that, if followed, allows you to recast yourself as a healthy, fit person using “controlled gene expression”. The “primal” part comes from the recognition that our basic human DNA is relatively unchanged from the past 10,000 years. As long as we understand what it took to evolve to that point, we can find ways to continue to influence gene expression that are in alignment with that pre-agricultural DNA.

Thanks again for your comments and questions, and please keep them coming.

Dollar Bin, ott1mo Flickr Photos (CC)

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About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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