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The Interaction Between Genes and Diet In Healthy Aging

Everybody knows or has heard of a remarkably long-lived person. Many have lived independently into their hundreds and passed away without experiencing the extreme debility we usually associate with very old age. And although everyone slows down, these exceptional people remain fit and sharp. I describe such individuals as members of the “Mindspan Elite,” people who not only live extremely long lives, but retain high cognitive performance and good physical health through their later years (I coined the term “mindspan” to mean the lifespan of the high-performance mind). Studies suggest that the Mindspan Elite age more slowly; in effect, are biologically younger than most people their age. It’s common to attribute such exceptional health to “good genes,” and that these golden genes put lucky bearers on a course toward happy and extreme mindspans.

Although good genes and medical advances can help some people live longer, healthier lives, most scientific investigations show that genes are responsible for only about a third of extended longevity, and that much of the rest is due to environmental factors above and beyond medical advances -- improvements in lifestyle, such as diet, sleep, mental stimulation, mood, and exercise. It seems that just about everyone with a platform extols the health benefits of a certain diet. Indeed, complementary research has repeatedly demonstrated the importance of diet and nutrition to health and longevity -- and the link between diet and longevity continues to grow.

Yet a hyperfocus on diet implies a “genes or diet” dichotomy, missing possibly the single most important point about the role genes play in longevity: genes and diet are interdependent. To promote cognitive and/or physical health, many gene variants require a complementary diet, one which matches an individual’s particular genetic makeup.

Diet May be The Most Controllable Determinant of Healthy Aging
When we think of a healthful diet, we often think of a Mediterranean diet, which numerous studies have proven as superior to most others -- especially to a typical Western diet. Studies have also characterized Asian diets as healthful. And in fact, many of the longest-lived people in the world are Japanese. In my book, The Mindspan Diet, I note that the Mindspan Elite are highly concentrated in areas with diets recognized as healthful. A high proportion of centenarians and supercentenarians (people age 110 and older) live, for example, in Japan, near the Mediterranean Sea in parts of France and Italy, and in the region of Spain Northeast of Madrid stretching north and westward to the north and western coasts above Portugal.

Mindspan Diet
People often reflexively attribute the geographic clustering of the Mindspan Elite “just to good genes.” But the genes of the Mindspan Elite vary considerably from region to region. Though the foods and diets of these people also seem varied, through extensive research, I’ve discovered that healthy agers in these regions share remarkably similar dietary characteristics -- especially concerning some critical nutrients and their interactions with key genes.

Here’s what we can learn about successful aging from the dietary habits of the world’s centenarians and supercentenarians, especially those who enjoy significant longevity of both body and mind:

The Mindspan Elite Typically Consume Foods That Restrict Iron Absorption
One of the most significant dietary habits of the Mindspan Elite is avoidance of foods promoting excessive iron absorption. For example, the typical diet in such regions is low in red meat.

People in such regions typically consume foods low or even deficient in iron, including non-fortified white rice and pasta, and olive oil. In fact, foods “fortified” or “enriched” with iron aren’t typically even available in these areas, in contrast to in the U.S., Northern and Western Europe, where enriched white flour is often the norm. Throughout the areas along the Mediterranean Sea where the Mindspan Elite cluster, dietary staples consist of non-enriched white flour bread and non-enriched semolina wheat pasta. And in Japan, the country with the highest concentration of the Mindspan Elite, the very bedrock of traditional cuisine is non-enriched white rice. For well over a century in these mindspan-leading regions, such refined, unfortified staples have provided more dietary energy (calories) than any other food.

Noodles
Contrast this reality with the near universal misconception that whole grains comprise the grain staples of these cultures. Yet decades of data and cultural profiles on the Mindspan Elite cuisines along the Mediterranean Sea and in Japan provide incontrovertible evidence disproving such claims. While the nutritional mainstream has converged on a monolithic message that whole grains should replace all refined grain foods, many scientific facts suggest that whole grains are not as healthful as they appear. For example, whole grains tend to contain various unhealthy substances -- including more toxins, and heavy metals such as arsenic, cadmium, and lead -- than do refined grains.

The Health Risks of Excessive Iron Are Well Documented
It’s no coincidence that the diets of the Mindspan Elite are rich in foods that contain low levels of iron or inhibit iron absorption. We’ve reached a scientific tipping point in understanding the health impact of excessive iron accumulation, which raises the risk of neurodegenerative conditions, including Alzheimer’s and Parkinson’s Disease, cancer, cardiovascular diseases, and a host of other serious conditions.

Scientific Evidence Tying Iron to Health Risks
Essentially every different major class of evidence has implicated iron in health risks, and the data have been accumulating for decades. The most credible kinds of evidence -- molecular and genetic evidence, controlled feeding experiments of animal models, and even clinical trial data -- have directly implicated iron in disease. To name just a few studies:

  • Distinguished biochemist Eugene Weinberg documented excessive iron as a central cause of numerous diseases in his 2004 book, “Exposing the Hidden Dangers of Iron.”
  • A landmark 2015 study, a multi-center longitudinal study contributed to by hundreds of distinguished scientists, who conducted dozens of studies, concluded that iron plays a key role in the development of Alzheimer’s Disease (The Alzheimer's Disease Neuroimaging Initiative, “Ferritin Levels in the Cerebrospinal Fluid Predict Alzheimer’s Disease Outcomes and are Regulated by APOE,” by Scott Ayton, Noel G. Faux, Ashley I. Bush. Nature Communications, May 19th, 2015).

How Iron Enters Your Body to Potentially Impact Internal Organs
Both your diet and/or your genetic makeup can lead you to build up excess iron, potentially damaging your internal organs: Iron typically enters the body through the consumption of foods and liquids, which alone can cause an overaccumulation of iron. In addition, changes in your DNA, known as genetic variants or mutations, can also interact even with what seems like a diet moderate in iron to cause iron excess. Hemochromatosis, for example, causes the body to absorb too much iron -- in some cases many times more than normal. Though most of the 1 in 5 people who carry such a variant don’t develop clinical hemochromatosis, many of them typically have excessive body iron. And the average iron level of individuals living in countries such as the U.S. already far exceeds what’s necessary.

How Iron Enters Your Central Nervous System
Once iron enters your body, your genetic makeup plays a key role not only in determining how much iron your body absorbs, but how much iron crosses the blood-brain barrier to your central nervous system and brain. Multiple scientific reports show that some genetic variants increase iron absorption into the body, and that the risks of disease associated with elevated iron within the body are further increased by other pathogenic genetic variants that transport excess iron to the nervous system and brain. This synergy greatly increases the risk of neurodegenerative diseases.

About half the US population carries at least one iron-related pathogenic variant: either a variant causing excessive iron accumulation in the body (at the most extreme levels, resulting in hemochromatosis), or a variant in the APOE gene, causing excessive iron transport to the central nervous system. In the rest of the world populations, the prevalence of at least one of these iron-related pathogenic variants occurs in 45%-to 65% of the population, depending on the geographic region. And that's only counting the prevalence of pathogenic variants in just these two -- of many -- iron-related genes.

Isn’t Iron Healthy, Even Essential?
Everyone needs a sufficient amount of iron. It is essential for life. Iron transports oxygen (in hemoglobin) to all parts of the body, and has many other indispensable cellular functions. But any amount of iron above sufficiency levels carries health risks. For example, humans absorb about 8-10% of the iron in the foods they eat. Although many people associate anemia (red blood cell deficiency) with “iron-poor blood,” which some menstruating girls and women may experience, several types of anemia don’t involve iron deficiency at all. So obtain the advice of your doctor before taking supplements or increasing red meat consumption.

Avoid Breakfast Cereals and Other Processed Foods High in Iron
Think twice about eating -- or letting your children eat -- processed foods high in iron, such as popular breakfast cereals. First, the US recommended daily allowance (USRDA) percentage for iron is designed for menstruating girls or women. For everyone else, even assuming no iron-related genetic variants, a healthy level of daily iron would be roughly half that percentage. Second, the USRDA for a particular cereal assumes you consume only 3/4 to 1 cup of cereal. But, of course, this underestimates how much people normally consume when they eat a bowl of cereal. Keep this all in mind when checking out the nutrition facts on your favorite cereal.

Fermented and Fermentable Food
The diet of the Mindspan Elite also generally includes an appetizer that contains a “fermented” food, such as vinegar in a salad, a pickled vegetable, or pickled fish, or sour dough bread.

Pickled Vegetables
Further, many members of the Mindspan Elite also moderately consume a fermented beverage during meals, alcohol. They also generally consume “fermentable” foods -- such as leaks, garlic, greens, grains, vegetables, and beans. Fermented and fermentable foods play a key role in promoting health, including optimizing the digestion of refined grains, by:

  • Slowing down overall digestion and absorption of sugar into the bloodstream (preempting potential spikes in blood sugar)
  • Stabilizing metabolism
  • Reducing risk of diabetes
  • Regulating body weight

Foods High in Polyphenols
Polyphenols are organic compounds that provide a variety of health benefits and reduce the body’s absorption of iron. The Mindspan Elite generally consume foods rich in these protective chemicals, found in beverages including coffee, black or green tea, cocoa, dark chocolate, herbal teas, as well as in vegetables, grains, and in fruit.

Green Tea


The 10 Dietary Habits of Highly Successful Agers - The Mindspan Diet

  1. Little or no red meat.
  2. Tea, coffee, or alcohol consumed with meals (the latter in moderation).
  3. Fermented appetizer -- typically vinegar with vegetables or fish (pickled, or dried).
  4. Non-enriched white rice, semolina pasta, white bread, and/or white sourdough bread (e.g., low glycemic index refined carbs, not fortified with iron).
  5. Moderate to high intake of high quality monounsaturated fat, such as from olive oil or canola oil; moderate intake of omega-3 fats from vegetables such as lettuce, cauliflower, spinach, etc.
  6. Vegetables -- such as greens -- and fruits -- such as berries, tomatoes, avocados, and grapes (e.g., foods high in phytochemicals, also contained in beverages including red wine, coffee, cocoa, tea, and herbal teas, including mint, chamomile and pennyroyal).
  7. Moderate to fairly high intake of fish and seafood (not deep fried).
  8. Less milk (moderate amounts of cheese, butter, and sour cream). These choices depend on an individual’s genetic makeup, as explained in The Mindspan Diet.
  9. More beans and other legumes.
  10. Less added sugar/moderate salt.

Testing for Iron Excess
Taking a panel of specific blood tests is the only way to know definitively if you have excess iron. One common test measures hemoglobin. However, the most important test is serum ferritin. Although a scandal in the 1990’s removed serum ferritin from the common blood testing panel, you can request it through healthcare providers. Though not covered by insurance, a serum ferritin test generally costs under $50 out-of-pocket. I believe current scientific evidence overwhelmingly suggests that the traditionally acceptable range of blood iron levels is too high. Further, modern medicine has arbitrarily set a much higher definition of healthy iron levels in men than in women. Simply because men typically have higher iron levels doesn’t mean those levels are harmless.

Blood Test
I consider healthy biomarker levels as follows:

  • 10-40 nanograms of ferritin
  • 12 to 13 grams per deciliter of hemoglobin (although even lower hemoglobin is common in centenarians).

How to Tell if You have a Genetic Predisposition to The Harmful Impacts of Iron
Sequencing your entire DNA (Whole Genome Sequencing) can identify whether you have genetic variants, not only predisposing you to the harmful effects of iron, but to other clinically relevant health conditions. According to your genetic makeup, your physician may then recommend measures to reduce your risk of disease by adjusting your diet, lifestyle, and potentially, medications.

The earlier you can practice preventive medicine and monitor for conditions you may have a predisposition for, the more you can reduce your risk of disease. If, for example, you have a genetic variant that increases your risk to the harmful impacts of iron, your doctor may recommend a regimen including avoidance of foods containing large quantities of absorbable iron, getting regular exercise to excrete iron build-up, taking iron chelation tablets, and/or undergoing bloodletting.

Try The Diet of the Mindspan Elite
I hope this article inspires you to try a new diet that can put you on a path to a healthier, longer life. According to the National institute on Aging, the global number of centenarians, people age 100 or older, is projected to increase 10-fold between 2010 and 2050. If more people tailor their diets and lifestyles to their genes, I believe even this projection will turn out to be an underestimation. If you start following the diet of the Mindspan Elite, maybe someday you’ll become one of them.

Emma Morano
Credit: Alessandro Grassani for The New York Times

Meet the World’s Oldest Living Person - Emma Morano, age 117
117-year-old Emma Morano of Italy’s Piedmont region, near the Mediterranean Sea, is the world's oldest living person whose date is verified. Emma lives independently and prepares her own meals. Her everyday menu includes white pasta for lunch, eggs, and a daily dose of her homemade brandy.

Preston Estep Ph.D. is Director of Gerontology at the Personal Genome Project at Harvard Medical School, author of The Mindspan Diet, and Chief Scientific Officer of Veritas Genetics.