The Mindspan Diet

Neurodegenerative disorders are on the rise in the U.S., Europe, and in most affluent nations of the world.

According to a recent study, deaths from Alzheimer’s disease and other dementias rose more than three-fold, and deaths from Parkinson’s disease doubled globally between 1990 and 2010.

Fortunately, scientific evidence indicates that we have substantial control over our risk for neurodegenerative diseases.

Dr. Preston Estep is an esteemed geneticist and the director of gerontology at the Personal Genome Project at Harvard Medical School.

In this interview with Life Extension®, Dr. Estep highlights the secrets of the “Mindspan Elite”—those populations that live longest with low levels of dementia.

Studying these populations—along with recent scientific evidence—has given Dr. Estep insights on how to extend both lifespan and mindspan.

He shares many of those ideas here for Life Extension® readers.

—Laurie Mathena

LE: Can you explain the difference between lifespan and mindspan?

Dr. Estep: Lifespan measures how long we live, but how fulfilling that life is depends on how well your mind works during that time. I use the term “mindspan” to capture this essential idea.

Lifespan refers only to longevity, while mindspan refers to the mind’s length of life plus its breadth and height of performance.

This pinnacle of living isn’t just a long lifespan, it is a maximum mindspan.

LE: Can you tell us about people you refer to as the Mindspan Elite?

Dr. Estep: People are living longer than ever. While this trend is good, there is a serious downside: Record numbers of people are experiencing greater levels of cognitive decline and other brain disorders in later life.

But some people seem mostly immune to such problems. I call these people the Mindspan Elite.

They live very long lives and remain as alert, active, and autonomous as people decades younger. Important discoveries from many sources have shed substantial light on the keys to their success, and now show the rest of us the way.

LE: After studying the Mindspan Elite, does it seem like their longevity is a result of genes or environment?

Dr. Estep: It is commonly believed that centenarians and supercentenarians have special genes that allow them to age slowly. Most experts agree that the contribution of genes explains only a small fraction of typical longevity, and a higher percentage of extreme longevity—maybe between 25% and 40% of extreme longevity.

That means environment is responsible for the remaining majority of the longevity equation, and diet is a major component of the environment.

When Japanese (who are part of the Mindspan Elite) move to other countries, their health typically goes downhill.

Japanese in the U.S. with the highest rates of disease, including Alzheimer’s disease and other dementias, have a more Western eating pattern. Their rates of dementia are similar to those of Americans of European ancestry.

So bad diet produces bad results—but luckily, this works both ways.

Many studies have shown that people who adopt healthy Asian and Mediterranean-style diets have lower levels of disease.

LE: What are some core diet commonalities of the Mindspan Elite?

Dr. Estep: Here is a short list:

• Less red meat and added sugar.
• Less liquid milk (moderate amounts of cheese, butter, sour cream).
• Moderate to fairly high amounts of fish and seafood, typically not deep-fried.
• More beans and other legumes.
• Fat consumption varies, but if it is high, then it is mostly monounsaturated (typically olive oil).
• Alcohol consumption varies but is routine, usually with meals, and is not extreme among the longest-lived.
• Abundant dietary phytochemicals, such as polyphenols and tannins, consumed with meals and present in fruits and vegetables, red wine, coffee, and tea.
• More fermented, pickled, and preserved foods, such as vinegar and dried fish.
• More greens. Key Mediterranean cuisines feature an abundance of greens and herbs. In Japan, sea vegetables (seaweed, kelp, etc.) are found in many meals.

LE: Many people erroneously promote a high-protein, low-carb diet. What can the Mindspan Elite teach us about protein?

Dr. Estep: Relatively low animal protein intake is a shared dietary attribute among Mindspan Elite regions and subcultures.

Research shows that animals raised on low-protein diets live longer than animals eating diets with typical amounts of protein.

The China Study, a well-known study done in the 1980s, found that dietary protein intake is a primary determinant of diseases in later life, including cardiovascular disease and cancers.

LE: What are key biomarkers we can use to determine our longevity and mindspan?

Dr. Estep: Some biomarkers are simply symptoms of a certain state or underlying process. But other biomarkers, such as telomere length, are more than just markers; they play critical roles in setting the pace of aging and senescence.

Telomeres are specialized stretches of DNA that protect the ends of chromosomes. Long, stable telomeres are robust predictors of good health and longevity. As we age, telomeres get broken down and become shorter.

In general, the shorter your telomeres are, the shorter your lifespan.

Most long-lived people in their eighties and nineties have telomeres as long as or longer than most people in their seventies.

LE: How can you influence the length of your telomeres?

Dr. Estep: The shortening of telomeres can be accelerated by certain environmental variables—including diet.

But here is the positive flip side: good diet and lifestyle factors can counteract this erosion.

Higher intake of omega-3 fats, good sleep, low stress, and routine exercise are all associated with longer telomere length.

LE: What other key biomarkers should people be testing?

Dr. Estep: Two of the most important and commonly measured cardiovascular biomarkers are cholesterol and triglyceride levels. If these are moderately elevated on their own, it’s not necessarily reason for alarm.

Longevity and mindspan are at much greater risk if these high biomarker levels are accompanied by high blood iron levels, which accelerate the oxidation of LDL cholesterol.

High oxidation plus high LDL is deadly for both your heart and your brain.

LE: Isn’t iron beneficial for the body?

Dr. Estep: Of all the dangerous double-edged swords, iron cuts the deepest of all.

The peril posed by iron is unique among all dietary minerals. It’s the most abundant and potent oxidant in the body, but your body doesn’t have a way to get rid of excess iron, unlike other minerals.

You can compare iron to a match in the presence of fuel and oxygen. In control, warmth and light are produced; out of control, the result is like a persistent, wind-driven wildfire.

Consider a car analogy: Dietary fats and sugars, like gasoline, are hydrocarbons that produce energy. Your body mixes this fuel with oxygen and then ignites it to create useful energy and heat.

We need iron to carry oxygen throughout the body for this essential process. But just as an older car rusts, so does your body.

Its rust comes in the form of deposits of “garbage”—for example, hemosiderin, lipofuscin, and amyloid plaques in the brain that are primary drivers of Alzheimer’s disease.

Rust also comes in the form of “damage,” such as oxidized components of cells and tissues (e.g., DNA and proteins), and iron is a primary driver in the creation of this garbage and damage.

The higher the iron burden in your body, the greater the burden of accumulated garbage and damage over time, especially to brain neurons.

LE: How does excess iron impact the brain specifically?

Dr. Estep: In youth, iron is a critical nutrient for proper brain development.

However, high body iron stores in adulthood increase the risk of Alzheimer’s disease, Parkinson’s disease, ALS (Lou Gehrig’s disease), stroke, and other diseases of the brain and nervous system.

In other words, we need lots of iron in youth, but as we get older, these amounts become harmful.

The brain typically has a higher concentration of iron than any other metal. Specific brain regions affected by very different neurodegenerative diseases have one commonality: They show high levels of iron deposits.

LE: Why do so many people have excess iron?

Dr. Estep: Because red meat consumption remains too high, and because of iron fortification. In the U.S. today, about half of dietary iron is obtained through fortified grain products.

Iron fortification is done with the best of intentions, but it is clear that low but sufficient iron poses no clear health risk to adults.

The problem with most iron-enriched grain products is that the iron is absorbed rapidly with large amounts of monosaccharide sugars from the breakdown of the starch in the grain.

This is a toxic and completely unnatural combination that produces unprecedented stresses on your body, especially your vasculature and your pancreas, which regulates insulin and glucose.

Some of the worst offenders are breakfast cereals that are hyper-enriched with iron.

And it is essential to understand that the amount of iron on nutritional labels is specific to menstruating women and is very misleading for everyone else. Older people and males need less than half of the recommended daily intake on food labels.

LE: So, red meats and iron-enriched grains are main sources of iron. Are there other largely invisible sources?

Dr. Estep: Veggie burgers used to consist of various beans and vegetables, but the new generation of plant-based meats, like Beyond and Impossible burgers taste more like meat because it was discovered recently that iron is a key ingredient that gives real meat its distinctive “meaty” flavor. There has been a lot of media coverage of these plant-based meats and many questions about whether or not they are good additions to a healthy diet. For pre-menopausal women and others with low iron, I think they are good substitutes for meat, but for everyone else, stick to low-iron, plant-based foods.

LE: As a geneticist, you have unique insights into how genes impact disease risk. Do genes also factor into your risk of Alzheimer’s disease?

Dr. Estep: Research scientists have turned up many clues about the genetic regulations of overall human and brain longevity, but two genes truly stand out, because they have by far the largest overall effects.

Those genes are called APOE and APP. Variants of both cause Alzheimer’s disease at an early age.

The APOE gene has repeatedly been proven to have the most significant longevity effect of any gene. It comes in three variant forms: e2, e3, and e4.

Everyone carries two copies of the APOE gene, but the two most problematic duos are the e3/e4 combination, which typically increases risk for Alzheimer’s disease by two to three times, and the e4/e4 combination, which increases risk by more than 10 times.

LE: Why are these genes so problematic for the brain?

Dr. Estep: Both genes are influenced by diet and lifestyle, since they interact with iron, and amplify the effects of iron in the brain.

Recent evidence has been building that implicates APOE in the transport of iron to the brain. In mid-2015 the APOE and iron connection was elevated to the level of a near certainty.

An international consortium of several Alzheimer’s disease studies published the results of an over seven-year study of three groups of people: non-demented, mild cognitive impairment, and Alzheimer’s disease.

They found that the cerebrospinal fluid level of ferritin (the main iron storage protein in the body) predicted the degree of cognitive decline—higher ferritin led to faster decline and dementia.

They further found that the APOE e4 variant was associated with higher cerebrospinal fluid ferritin, more evidence that the e4 variant is responsible for raising iron load in the brain and driving cellular damage, tissue loss, and plaque formation.

LE: What about APP?

Dr. Estep: The gene for APP (amyloid precursor protein) causes the plaque (known as amyloid beta) seen in brains afflicted with Alzheimer’s disease. Research suggests that the job of APP in the brain is to protect cells and tissue from iron’s oxidative damage.

The APP gene protects the brain, but in the long run also harms the brain through the long-term consequences of this mode of protection.

There is a basic formula:

GENES + ENVIRONMENT = TRAIT.

Dietary iron is the key environmental co-conspirator. So, in this case:

COMMON APP VARIANT + HIGH IRON = ALZHEIMER’S DISEASE.

Adding APOE e4 to the equation increases risk. Reducing dietary iron improves the ENVIRONMENT part of the equation and also reduces Alzheimer’s risk.

This is extremely important because more than 99% of us carry the common variant of APP, and our best option right now for reducing risk of Alzheimer’s disease is to exert control through environmental regulators of risk.

LE: Are there other genes we should be concerned about?

Dr. Estep: Other problematic variants are found in genes governing absorption of iron from food, and some of these are very common. About a quarter of the U.S. population has at least one copy of the APOE e4 variant, but another quarter has one or more variants in the HFE gene that increase absorption of iron from food, increasing the risk of iron overload, or hemochromatosis. The HFE gene is involved in regulating how much iron is absorbed from food, and the body has no natural mechanism for regulating iron balance by getting rid of iron once it is absorbed. So, it is critical to measure iron levels to ensure that overload is avoided preventively, because it is difficult to reverse iron overload, although blood donation (phlebotomy) and the use of iron chelators are helpful.

LE: While too much iron can clearly be problematic, low iron levels can cause their own concerns, such as anemia and increased susceptibility to infections. What is the ideal range of iron levels in the body?

Dr. Estep: Again, ferritin is the main iron storage protein in the body, and serum ferritin is a key biomarker that provides the best non-invasive measure of the amount of iron stored in the body.

For men and women, aim for 10 to 40 ng/mL (standard units), or micrograms per liter (international units) for maximum health benefits. This range is based on historical levels in Japanese women. They have the lowest iron levels in the developed world, the longest lives, and low rates of Alzheimer’s disease.

LE: What’s your key takeaway for readers to help understand extending their mindspan?

Dr. Estep: When The Mindspan Diet was published a few years ago lots of evidence pointed to iron as a key regulator of mindspan, but it was mostly circumstantial and provided statistical association but not clear evidence of causation. More recently, the largest and most advanced studies of human longevity* have strongly supported my conclusions about the importance of iron, showing that excess iron reduces longevity and that it isn’t merely associated with, but is a primary cause, of accelerated aging.

Recent research also indicates that Alzheimer’s disease is a close second to cancer as a cause of death in developed nations, and excess iron increases the risk of both these and other leading causes of death.

So, the bottom line is that iron is a critical nutrient for proper functioning of the body and mind, but I can’t emphasize enough that most adults in developed countries get far too much of it. And the only way for someone to know if they are at risk is to test serum ferritin and other critical markers of iron. When your life depends on it, don’t guess, test.

LE: Please tell us about your current projects.

Dr. Estep: In early 2020 I was planning the launch of a venture fund focused on starting and investing in biotech companies involved in increasing longevity and enhancing mindspan, but like many other people my plans changed as the pandemic unfolded. My main focus for the past year-and-a-half has been the Rapid Deployment Vaccine Collaborative (Radvac). As the pandemic gradually winds down I’m returning to focus on longevity/mindspan biotech startups and venture funding.

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.

* https://www.sciencedirect.com/science/article/pii/S0261561420303368, https://www.nature.com/articles/s41467-020-17312-3

Dr. Preston Estep received his doctorate from Harvard University. He is Director of Gerontology and advisor to the Personal Genome Project at Harvard Medical School. He has founded or is a scientific adviser to many leading biotech startup companies. He is the author of the book The Mindspan Diet and has addressed professional and lay audiences around the world on a range of topics in biomedicine including mindspan, genetic testing and whole genome DNA sequencing, vaccines, and space biomedicine.

The Mindspan Diet was published by Ballantine Books, an imprint of Random House, a division of Penguin Random House LLC. Excerpts reprinted by permission.

To order a copy of The Mindspan Diet visit Amazon.com