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Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

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April 28, 2008

Dear Mark: Gene Expression

By Mark Sisson
38 Comments

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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38 Comments on "Dear Mark: Gene Expression"

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Tom
8 years 5 months ago

Actually, we are understanding that it is even more complex. Lifestyle choices such as nutrition, smoking toxins etc. of the mother can effect the kids gene expression patterns. Do a search on epigenetics and methylation if you are interested. But basically, DNA methylation (a natural chemical modification of the DNA) is regulated by environment and here is the neat part it can be passed on to the next generation. So the pattern of inheritance is not just the A’s T’s G’s and C’s of the DNA but also the additional decorations on those bases.

Mark Sisson
8 years 5 months ago

To that effect, recent studies show that mothers who eat lots of carbs and then become insulin resistant cause their developing fetuses to be insulin resistant, giving the offspring a disadvantage from birth. The good news is that this disadvantage can be overcome with appropriate dietary changes.

tatsujin
8 years 5 months ago

Mark,
Thank you once again for clearly explaining the basics of some very complicated stuff.

This takes personal responsibility and responsbility towards your children to a whole new level.

Marc

Sasquatch
8 years 5 months ago

I agree that genes don’t forge destiny. There’s also a lot of regulation that goes on outside of gene expression, in how proteins interact with one another and affect signaling pathways. Basically, it’s really complicated and no one understands it all. But our ancestors seemed to be getting it right despite having our genes so they’re a good example for us.

Aaron
8 years 5 months ago

It is amazing that we are beginning to understand WHY things we have always thought were healthy (exercise, eating healthy, good sleep etc.) work. And not only that but what TYPE of exercise, diet etc. work at the cellular and genetic level to steer gene expression in the direction desired. The Primal Blueprint is the health philosophy of the 21st century. I can’t wait to learn more. Thanks, Mark.

Cindy
Cindy
8 years 5 months ago

That makes so much sense, I’m tired of hearing my friends blame their ailments on “bad genes.” Because I’m a bit a naturalist, I’ll use the garden metaphor. It’s not the seeds you’re given, it’s how you nurture them.

JohnSon
JohnSon
8 years 5 months ago

As more research is done and as this information becomes available I’d be interested to hear more about what one can do to achieve a desired physical effect. Or is all this going to do is tell us what we already know? Eat well, sleep well, stay active etc. It would be cool to find previously unknown body hacks. Though, I suppose some of the stuff MDA has already published is sort of body hack material… e.g. natural production of HGH, chronic cardio troubles etc.

Tina
Tina
8 years 5 months ago

“The “primal” part comes from the recognition that our basic human DNA is relatively unchanged from the past 10,000 years.”

Which is where your Primal arguments fall to shambles since this simply isn’t true. Genetically we have little in common with late Paleo people, let alone earlier ones. Evolution is known to occur much faster than you give it credit for and we are not stuck in the mold as you imply. Genetic expression adds even greater options for diversity, which you rightly bring up. But you should focus on a Modern Blueprint instead of the fantasy stuff.

Mark Sisson
8 years 5 months ago
Tina,Tim, That’s the same erroneous assumption we discussed last month. Humans may be exhibiting a widening range of SNPs and slight gene variances, but that does not mean that we are evolving at a faster rate. It just means that mutations and changes are not selected out and that normal “drift” happens at a greater rate due to sheer numbers. In fact, since there is no longer any effective selection pressure on our species (no predators, no real threat of starvation forcing us to adapt anew) and a nearly unlimited ability to reproduce, we have ceased to evolve in the… Read more »
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[…] Dear Mark: Gene Expression […]

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[…] stuff really floats our boat. The last few weeks we’ve brought you a Dear Mark primer on gene expression as well as news on recent studies examining the role of lifestyle/environment on genetic […]

Matt
Matt
7 years 8 months ago

Read ‘Biology of Belief’ by Bruce Lipton PhD and ‘Molecules of Emotion’ by Candice Pert PhD

Mark Sisson
7 years 8 months ago

Lipton certainly has a handle on gene expression and the absolute control we have

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[…] Improved Gene Expression […]

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[…] with yourself, and don’t expect the impossible. I am a strong believer in one’s ability to control their gene expression, reprogram their body, and become a healthier individual, but you aren’t going to sprout a few […]

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[…] While there are many things we can do (or eat) today that very closely approximate what Grok did to trigger positive gene expression, there are also a number of obstacles that can thwart our attempts to be as Primal as possible. […]

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[…] of a dramatic study highlighting (guess what) gene expression were published last week by the National Academy of Sciences, and suddenly the popular media is […]

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[…] good way to look at this is seeing it as a recipe: Everyone the DNA “recipe” to build a human being. The DNA itself is not really so much a “blueprint” […]

trackback

[…] degenerative disease risk. If you’re relatively new to MDA, take a look-see at my past articles (Gene Expression, What I Mean By “Reprogramming Your Genes”, Gene Expression: Location, Location, […]

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6 years 3 months ago
[…] What about Calories!? Yes, calories are very important for those of you that are trying to lose weight. That is why anyone who simply reduces their caloric intake below what they burn as a result of basal metabolism and additional activity will lose weight. Unfortunately, however, these people often center their diets around refined grain-carbohydrates and sugars because they want to “enjoy” the few calories that they allow themselves to eat. Though it is certainly true that overall weight-loss is a result of eating fewer calories than you burn, a calorie isn’t just a calorie. Eating a days worth… Read more »
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[…] of a dramatic study highlighting (guess what) gene expression were published last week by the National Academy of Sciences, and suddenly the popular media is […]

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[…] going to grab a quote from Mark Sisson to give a good analogy. This came from here. Please go read it. Everyone the DNA “recipe” to build a human being. The DNA itself is not […]

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[…] This is what The Primal Blueprint is all about. It’s why the sub-title of my book is “Reprogram Your Genes for Effortless Weight Loss, Vibrant Health and Boundless Energy”. And it’s what we talk about (either directly or indirectly) day-in and day-out here at Mark’s Daily Apple. We tend to focus on the practical, but epigenetics is at the heart of why we do what we do. Living like Grok just happens to be the best starting point for directing gene expression. […]

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[…] glycemic/paleo nutrition. Bringing attention to this evidence, along with the potential for positive epigenetic changes, is the key to promoting paleo and primal […]

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[…] to Neu5Gc. Why is this important? Sialic acids act as “contact points” for our cells to interact with the environment and other cells, and the latest research indicates that mice with the humanesque CMAH mutation are […]

Jann Taber
5 years 4 months ago

Mark, have you heard of the nutrutional supplement Protandim? The formulation was develped by the scientist that discovered SOD 40 something-years ago, Dr. Joe McCord.

ABC PrimeTime did an investigative report on it. http://www.watchABCreport.com

I’d love your thoughts on whether or not it fits with your Primal Blueprint concept of gene expression.

You can also go to pubmed.gov and type in Protandim to see the peer reviewed studies that have been released since the ABC investigation.

Gabriel
Gabriel
4 years 6 months ago

Mark, I would love to hear your take on the Protandim studies as well. I have a family member getting into that product, and I would love to know what is real vs what is hype.

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[…] or negatively influence gene expression.  Most people agree that smoking causes cancer.  In this article, Mark Sisson explains how our bodies can become insulin resistant from a diet that is high in […]

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[…] going to utilize a few quotes from one of my favorite bloggers, Mark Sisson, to introduce this concept: while your genes are “fixed”, the expression of those genes – […]

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[…] to place a wager, I’d bet that it has to do with the proopiomelanocortin (POMC) gene, whose expression triggers the secretion of melanocyte-stimulating hormone (MSH, a hormone that darkens the skin and […]

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[…] to place a wager, I’d bet that it has to do with the proopiomelanocortin (POMC) gene, whose expression triggers the secretion of melanocyte-stimulating hormone (MSH, a hormone that darkens the skin and […]

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[…] as I always like to do, let’s talk about epigenetics and gene expression. Most people think of T1D as a “genetic disease,” as in you “just get it” […]

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2 years 7 months ago

[…] with yourself, and don’t expect the impossible. I am a strong believer in one’s ability to control their gene expression, reprogram their body, and become a healthier individual, but you […]

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[…] spend billions of dollars researching which gene “lights up” or which protein levels rise all in the name of better understanding the physiological mechanisms […]

Ryan
Ryan
1 year 1 month ago

Also interested in your take on Protandim Mark, specifically whether or not the idea of too many antioxidants is toxic, which they claim to solve with the senergy of their formula…?

Jeff
Jeff
9 months 5 days ago

Any responses or thoughts on Protandim? I haven’t seen any, but new to the site, so I apologize if they are posted somewhere.

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[…] entire premise of the Primal Blueprint is enabling you to be the architect of your health and happiness. If we can identify the […]

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[…] entire premise of the Primal Blueprint is enabling you to be the architect of your health and happiness. If we can identify the […]

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