All the notes were taken directly from the source mentioned.

– – –

There comes a point where we need to stop just pulling people out of the river. We need to go upstream and find out why they’re falling in. —BISHOP DESMOND TUTU

This is what happened to a hapless mythical Greek named Tithonus, who asked the gods for eternal life. To his joy, the gods granted his wish. But because he forgot to ask for eternal youth as well, his body continued to decay.

In 1900, life expectancy hovered somewhere south of age fifty, and most people were likely to die from “fast” causes: accidents, injuries, and infectious diseases of various kinds. Since then, slow death has supplanted fast death.

Four Horsemen: heart disease, cancer, neurodegenerative disease, or type 2 diabetes and related metabolic dysfunction.

Longevity has two components. The first is how long you live, your chronological lifespan, but the second and equally important part is how well you live—the quality of your years. This is called healthspan.

Where am I headed from here? What’s my future trajectory? Already, in midlife, the warning signs abound.

The only way to create a better future for yourself—to set yourself on a better trajectory—is to start thinking about it and taking action now.

We had an amazing ability to save lives and restore full function to broken bodies, even reviving patients who were nearly dead. But we were markedly less successful at helping our patients with chronic conditions, such as cancer, cardiovascular disease, or neurological disease, evade slow death.

While the prevalence of each of the Horsemen diseases increases sharply with age, they typically begin much earlier than we recognize, and they generally take a very long time to kill you.

This simple preventive measure (not smoking) has saved more lives than any late-stage intervention that medicine has devised. Yet mainstream medicine still insists on waiting until the point of diagnosis before we intervene.

Atherosclerosis, or heart disease,

I am not a laboratory scientist or clinical researcher but more of a translator, helping you understand and apply these insights.

We have to get the meaning of the words exactly right (the science), while also capturing the tone, the nuance, the feeling, and the rhythm (the art). Similarly, my approach to longevity is firmly rooted in science, but there is also a good deal of art in figuring out how and when to apply our knowledge to you, the patient, with your specific genes, your history and habits, and your goals.

The time to repair the roof is when the sun is shining. —JOHN F. KENNEDY

Medicine 2.0 arrived in the mid-nineteenth century with the advent of the germ theory of disease, which supplanted the idea that most illness was spread by “miasmas,” or bad air. This led to improved sanitary practices by physicians and ultimately the development of antibiotics. But it was far from a clean transition; it’s not as though one day Louis Pasteur, Joseph Lister, and Robert Koch simply published their groundbreaking studies.

The foundation was laid back in 1628, when Sir Francis Bacon first articulated what we now know as the scientific method.

Yet three centuries elapsed between Bacon’s essay and the discovery of penicillin, the true game-changer of Medicine 2.0. Medicine 2.0 was transformational. It is a defining feature of our civilization, a scientific war machine that has eradicated deadly diseases such as polio and smallpox. Its successes continued with the containment of HIV and AIDS in the 1990s and 2000s, turning what had seemed like a plague that threatened all humanity into a manageable chronic disease. I’d put the recent cure of hepatitis C right up there as well.

While books like this always trumpet the fact that lifespans have nearly doubled since the late 1800s, the lion’s share of that progress may have resulted entirely from antibiotics and improved sanitation, as Steven Johnson points out in his book Extra Life. The Northwestern University economist Robert J. Gordon analyzed mortality data going back to 1900 (see figure 1) and found that if you subtract out deaths from the eight top infectious diseases, which were largely brought under control by the advent of antibiotics in the 1930s, overall mortality rates declined relatively little over the course of the twentieth century.

The goal of this new medicine—which I call Medicine 3.0—is not to patch people up and get them out the door, removing their tumors and hoping for the best, but rather to prevent the tumors from appearing and spreading in the first place.

This technology, known as continuous glucose monitoring (CGM), lets me observe how their individual metabolism responds to a certain eating pattern and make changes to their diet quickly.

There are few insurance reimbursement codes for most of the largely preventive interventions that I believe are necessary to extend lifespan and healthspan.

Medicine 3.0 demands much more from you, the patient: You must be well informed, medically literate to a reasonable degree, clear-eyed about your goals, and cognizant of the true nature of risk. You must be willing to change ingrained habits, accept new challenges, and venture outside of your comfort zone if necessary. You are always participating, never passive. You confront problems, even uncomfortable or scary ones, rather than ignoring them until it’s too late. You have skin in the game, in a very literal sense. And you make important decisions.

The point is that the tactics are what you do when you are actually in the ring. The strategy is the harder part, because it requires careful study of one’s opponent, identifying his strengths and weaknesses, and figuring¬†out¬†how to use both to your advantage, well before actually stepping in the ring.

maximum volume of oxygen uptake (VO2 max)

…while actual death is inevitable, this deterioration that we’re talking about is less so. Not everyone who dies in their eighties or nineties passes through the valleys of cognitive, physical, or emotional destruction on the way there.

Medicine 3.0 fall into five broad domains: exercise, nutrition, sleep, emotional health, and exogenous molecules, meaning drugs, hormones, or supplements.

…we will break down this thing called exercise into its most important components: strength, stability, aerobic efficiency, and peak aerobic capacity.

Randomized controlled trials are used to determine cause and effect in relatively simple, short-term situations.

…if a given intervention can be shown to extend lifespan or healthspan in multiple species spanning a billion years of evolution, for example, from worms to monkeys, then I am inclined to take it seriously.

Mendelian randomization, or MR for short. MR helps bridge the gap between randomized controlled trials, which can establish causality, and pure epidemiology, which often cannot.

…biology we can rarely “prove” anything definitively the way we can in mathematics. Living systems are messy, and confounding, and complex, and our understanding of even fairly simple things is constantly evolving. The best we can hope for is reducing our uncertainty.

…we are seeking the tactics that are likeliest, based on what we know now, to deliver a better-than-average return on our capital, while operating within our own individual tolerance for risk.

Can we, through our behaviors, somehow reap the same benefits that centenarians get for “free” via their genes? Or to put it more technically, can we mimic the centenarians’ phenotype, the physical traits that enable them to resist disease and survive for so long, even if we lack their genotype?

…to live longer with good function and without chronic disease, and with a briefer period of morbidity at the end of our lives.

It codes for a protein called APOE (apolipoprotein E) that is involved in cholesterol transport and processing, and it has three variants: e2, e3, and e4. Of these, e3 is the most common by far, but having one or two copies of the e4 variant seems to multiply one’s risk of developing Alzheimer’s disease by a factor of between two and twelve.

We had come because rapamycin had been demonstrated to do something that no other drug had ever done before: extend maximum lifespan in a mammal. This discovery came about at least in part thanks to the work of one member of our group, David Sabatini, who was then a professor of biology at MIT’s Whitehead Institute.

He named it rapamycin, after Rapa Nui, the native name for Easter Island (mycin is the suffix typically applied to antimicrobial agents).

…rapamycin acted directly on a very important intracellular protein complex called mTOR

When food is plentiful, mTOR is activated and the cell (or the organism) goes into growth mode, producing new proteins and undergoing cell division, as with the ultimate goal of reproduction. When nutrients are scarce, mTOR is suppressed and cells go into a kind of “recycling” mode, breaking down cellular components and generally cleaning house. Cell division and growth slow down or stop, and reproduction is put on hold to allow the organism to conserve energy.

…no other molecule had been shown to extend lifespan in a mammal. Ever.

It has also been shown to do so in yeast and fruit flies, sometimes alongside genetic manipulations that reduced mTOR activity. Thus, a reasonable person could conclude that there was something good about turning down mTOR, at least temporarily—and that rapamycin may have potential as a longevity-enhancing drug.

Caloric restriction without malnutrition, commonly abbreviated as CR, is a precise experimental method where one group of animals (the controls) are fed ad libitum, meaning they eat as much as they want, while the experimental group or groups are given a similar diet containing all the necessary nutrients but 25 or 30 percent fewer total calories (more or less). The restricted animals are then compared against the controls. The results have been remarkably consistent. Studies dating back to the 1930s have found that limiting caloric intake can lengthen the lifespan of a mouse or a rat by anywhere from 15 to 45 percent, depending on the age of onset and degree of restriction. Not only that, but the underfed animals also seem to be markedly healthier for their age, developing fewer spontaneous tumors than normally fed mice. CR seems to improve their healthspan in addition to their lifespan.

Numerous labs have found that restricting caloric intake lengthens lifespan not only in rats and mice (usually) but also in yeast, worms, flies, fish, hamsters, dogs, and even, weirdly, spiders.

For one, CR’s usefulness remains doubtful outside of the lab; very lean animals may be more susceptible to death from infection or cold temperatures.

The first of these is an enzyme called AMP-activated protein kinase, or AMPK for short. AMPK is like the low-fuel light on the dashboard of your car: when it senses low levels of nutrients (fuel), it activates, triggering a cascade of actions. While this typically happens as a response to lack of nutrients, AMPK is also activated when we exercise, responding to the transient drop in nutrient levels. Just as you would change your itinerary if your fuel light came on, heading for the nearest gas station rather than Grandma’s house, AMPK prompts the cell to conserve and seek alternative sources of energy.

It does this first by stimulating the production of new mitochondria, the tiny organelles that produce energy in the cell, via a process called mitochondrial biogenesis. Over time—or with disuse—our mitochondria become vulnerable to oxidative stress and genomic damage, leading to dysfunction and failure. Restricting the amount of nutrients that are available, via dietary restriction or exercise, triggers the production of newer, more efficient mitochondria to replace old and damaged ones. These fresh mitochondria help the cell produce more ATP, the cellular energy currency, with the fuel it does have. AMPK also prompts the body to provide more fuel for these new mitochondria, by producing glucose in the liver (which we’ll talk about in the next chapter) and releasing energy stored in fat cells.

More importantly, AMPK works to inhibit the activity of mTOR, the cellular growth regulator. Specifically, it seems to be a drop in amino acids that induces mTOR to shut down, and with it all the anabolic (growth) processes that mTOR controls. Instead of making new proteins and undergoing cell division, the cell goes into a more fuel-efficient and stress-resistant mode, activating an important cellular recycling process called autophagy, which means “self-eating” (or better yet, “self-devouring”).

Autophagy represents the catabolic side of metabolism, when the cell stops producing new proteins and instead begins to break down old proteins and other cellular structures into their amino acid components, using the scavenged materials to build new ones. It’s a form of cellular recycling, cleaning out the accumulated junk in the cell and repurposing it or disposing of it.

This cellular cleanup is carried out by specialized organelles called lysosomes, which package up the old proteins and other detritus, including pathogens, and grind them down (via enzymes) for reuse. In addition, the lysosomes also break up and destroy things called aggregates, which are clumps of damaged proteins that accumulate over time.

Giving the drug daily, as is typically done with transplant patients, appears to inhibit both complexes, while dosing the drug briefly or cyclically inhibits mainly mTORC1, unlocking its longevity-related benefits, with fewer unwanted side effects.

Rapamycin seems to reduce these inflammatory cytokines. It also improves cancer surveillance, the ways in which our body, most likely the immune system, detects and eliminates cancer cells.

Metformin has been taken by millions of people for years. Over time, researchers noticed (and studies appeared to confirm) that patients on metformin appeared to have a lower incidence of cancer than the general population. One large 2014 analysis seemed to show that diabetics on metformin actually lived longer than nondiabetics, which is striking.

NAFLD and NASH are basically two stages of the same disease. NAFLD is the first stage, caused by (in short) more fat entering the liver or being produced there than exiting it. The next step down the metabolic gangplank is NASH, which is basically NAFLD plus inflammation, similar to hepatitis but without a viral infection.

Both NAFLD and NASH are still reversible. If you can somehow remove the fat from the liver (most commonly via weight loss), the inflammation will resolve, and liver function returns to normal.

Type 2 diabetes is technically a distinct disease, defined very clearly by glucose metrics, but I view it as simply the last stop on a railway line passing through several other stations, including hyperinsulinemia, prediabetes, and NAFLD/NASH.

Today we call this cluster of problems “metabolic syndrome” (or MetSyn), and it is defined in terms of the following five criteria: high blood pressure (>130/85) high triglycerides (>150 mg/dL) low HDL cholesterol (<40 mg/dL in men or <50 mg/dL in women) central adiposity (waist circumference >40 inches in men or >35 in women) elevated fasting glucose (>110 mg/dL)

Metabolism is the process by which we take in nutrients and break them down for use in the body.

At the risk of oversimplifying a bit, the carbohydrate from our doughnut has two possible fates. First, it can be converted into glycogen, the storage form of glucose, suitable for use in the near term. About 75 percent of this glycogen ends up in skeletal muscle and the other 25¬†percent goes to the liver, although this ratio can vary. An adult male can typically store a total of about 1,600 calories worth of glycogen between these two sites, or about enough energy for two hours of vigorous endurance exercise. This is why if you are running a marathon or doing a long bike ride, and do not replenish your fuel stores in some way, you are likely to “bonk,” or run out of energy.

One of the liver’s many important jobs is to convert this stored glycogen back to glucose and then to release it as needed to maintain blood glucose levels at a steady state, known as glucose homeostasis.

Consider that five grams of glucose, spread out across one’s entire circulatory system, is normal, while seven grams—a teaspoon and a half—means you have diabetes.

Even a relatively lean adult may carry ten kilograms of fat in their body, representing a whopping ninety thousand calories of stored energy.

Insulin helps shuttle the glucose to where it’s needed, while maintaining glucose homeostasis.

Think of fat as acting like a kind of metabolic buffer zone, absorbing excess energy and storing it safely until it is needed. If

As more calories flood into your subcutaneous fat tissue, it eventually reaches capacity and the surplus begins spilling over into other areas of your body: into your blood, as excess triglycerides; into your liver, contributing to NAFLD; into your muscle tissue, contributing directly to insulin resistance in the muscle

This is why I insist my patients undergo a DEXA scan annually—and I am far more interested in their visceral fat than their total body fat.

Insulin resistance is a term that we hear a lot, but what does it really mean? Technically, it means that cells, initially muscle cells, have stopped listening to insulin’s signals,

… fat spillover helps initiate insulin resistance, which results in the accumulation of still more fat, eventually impairing our ability to store calories as anything other than fat.

Evolution wants us to get fat when nutrients are abundant: the more energy we could store, in our ancestral past, the greater our chances of survival and successful reproduction. We needed to be able to endure periods of time without much food, and natural selection obliged, endowing us with genes that helped us conserve and store energy in the form of fat. That enabled our distant ancestors to survive periods of famine, cold climates, and physiologic stressors such as illness and pregnancy.

…is very difficult to get fat from eating too many apples, for example, because the fructose in the apple enters our system relatively slowly, mixed with fiber and water, and our gut and our metabolism can handle it normally. But if we are drinking quarts of apple juice, it’s a different story,

…fructose basically tricks our metabolism into thinking that we are depleting energy—and need to take in still more food and store more energy as fat.

I monitor several biomarkers related to metabolism, keeping a watchful eye for things like elevated uric acid, elevated homocysteine, chronic inflammation, and even mildly elevated ALT liver enzymes.

I watch the ratio of triglycerides to HDL cholesterol (it should be less than 2:1 or better¬†yet, less than 1:1), as well as levels of VLDL, a lipoprotein that carries triglycerides—all

But the first thing I look for, the canary in the coal mine of metabolic disorder, is elevated insulin.

One test that I like to give patients is the oral glucose tolerance test, or OGTT, where the patient swallows ten ounces of a sickly-sweet, almost undrinkable beverage called Glucola that contains seventy-five grams of pure glucose, or about twice as much sugar as in a regular Coca-Cola.[*6] We then measure the patient’s glucose and their insulin, every thirty minutes over the next two hours. Typically, their blood glucose levels will rise, followed by a peak in insulin, but then the glucose will steadily decrease as insulin does its job and removes it from circulation. On the surface, this is fine: insulin has done its job and brought glucose under control. But the insulin in someone at the early stages of insulin resistance will rise very dramatically in the first thirty minutes and then remain elevated, or even rise further, over the next hour.

There is some risk involved in action, there always is. But there is far more risk in failure to act. —HARRY S. TRUMAN

What is the most common “presentation” (or symptom) of heart disease? It wasn’t chest pain, left arm pain, or shortness of breath, the most common answers; it was sudden death.

Globally, heart disease and stroke (or cerebrovascular disease), which I lump together under the single heading of atherosclerotic cardiovascular disease, or ASCVD, represent the leading cause of death, killing an estimated 2,300 people every day in the United States, according to the CDC—more than any other cause, including cancer. It’s not just men who are at risk: American women are up to ten times more likely to die from atherosclerotic disease than from breast cancer (not a typo: one in three versus one in thirty).

While heart disease is the most prevalent age-related condition, it is also more easily prevented than either cancer or Alzheimer’s disease. We know a lot about how and why it begins and the manner in which it progresses. While it can’t exactly be cured or reversed the way type 2 diabetes (sometimes) can, it is relatively easy to delay if you’re smart and you get on the case early.

Because cholesterol belongs to the lipid family (that is, fats), it is not water soluble and thus cannot dissolve in our plasma like glucose or sodium and travel freely through our circulation. So it must be carted around in tiny spherical particles called lipoproteins—the final “L” in LDL and HDL—which act like little cargo submarines. As their name suggests, these lipoproteins are part lipid (inside) and part protein (outside); the protein is essentially the vessel that allows them to travel in our plasma while carrying their water-insoluble cargo of lipids, including cholesterol, triglycerides, and phospholipids, plus vitamins and other proteins that need to be distributed to our distant tissues.

The reason they’re called high- and low-density lipoproteins (HDL and LDL, respectively) has to do with the amount of fat relative to protein that each one carries. LDLs carry more lipids, while HDLs carry more protein in relation to fat, and are therefore more dense. Also, these particles (and other lipoproteins) frequently exchange cargo with one another, which is part of what drives me crazy about labeling them “good” and “bad.” When an HDL transfers its “good cholesterol” to an LDL particle, does that cholesterol suddenly become “bad”? The answer is no—because it’s not the cholesterol per se that causes problems but the nature of the particle in which it’s transported. Each lipoprotein particle is enwrapped by one or more large molecules, called apolipoproteins, that provide structure, stability, and, most importantly solubility to the particle. HDL particles are wrapped in a type of molecule called apolipoprotein A (or apoA), while LDL is encased in apolipoprotein B (or apoB). This distinction may seem trivial, but it goes to the very root cause of atherosclerotic disease: every single lipoprotein that contributes to atherosclerosis—not only LDL but several others[*1]—carries this apoB protein signature.

Fully half of all major adverse cardiovascular events in men (and a third of those in women), such as heart attack, stroke, or any procedure involving a stent or a graft, occur before the age of sixty-five.

…we have to know how many of these apoB particles are circulating in your bloodstream. That number is much more relevant than the total quantity of cholesterol that these particles are carrying.

There may have been other bad things happening there as well, but because I did not have a CT angiogram at this time, I had no sense of what kind of damage existed elsewhere in my coronary arteries. Anything shy of calcification is not identified by the calcium score.

I have all my patients tested for apoB regularly, and you should ask for the same test the next time you see your doctor.

I take a very hard line on lowering apoB, the particle that causes all this trouble. (In short: get it as low as possible, as early as possible.)

…when a patient comes to me and says their father or grandfather or aunt, or all three, died of “premature” heart disease, elevated Lp(a) is the first thing I look for.

…if you have a history of premature heart attacks in your family, you should definitely ask for an Lp(a) test.

Though we can’t reduce Lp(a) directly, beyond what a PCSK9 inhibitor can do, we can lower the remaining apoB concentration sufficiently that we can reduce a patient’s overall risk.

Monounsaturated fats, found in high quantities in extra virgin olive oil, macadamia nuts, and avocados (among other foods), do not have this effect, so I tend to push my patients to consume more of these, up to about 60 percent of total fat intake. The point is not necessarily to limit fat overall but to shift to fats that promote a better lipid profile.

Typically our first line of defense (or attack), statins inhibit cholesterol synthesis, prompting the liver to increase the expression of LDLR, taking more LDL out of circulation. They may have other benefits too, including an apparent anti-inflammatory effect, so while I don’t think statins should be dissolved into the drinking water, as some have suggested, I do think they are very helpful drugs for reducing apoB or LDL concentration in many patients.

Ten years is far too short a time horizon. If we want to reduce deaths from cardiovascular disease, we need to begin thinking about prevention in people in their forties and even thirties.

While there are seven statins on the market, I tend to start with rosuvastatin (Crestor)

I want to knock someone’s apoB concentration down to 20 or 30 mg/dL, about where it would be for a child.

For people who can’t tolerate statins, I like to use a newer drug, called bempedoic acid (Nexletol),

…cancer still kills Americans at almost exactly the same rate as it did fifty years ago. We have made some progress against a few specific cancers, notably leukemia (especially childhood leukemia, as I noted earlier).

Metastatic cancers can be slowed by chemotherapy, but they virtually always come back, often more resistant to treatment than ever. Our benchmark for success in a patient, or remission, is typically five-year survival, nothing more.

Far too often, we discover tumors only when they cause other symptoms, by which point they are often too locally advanced to be removed—or worse, the cancer has already spread to other parts of the body.

…cancer prevention is tricky, because we do not yet fully understand what drives the initiation and progression of the disease with the same resolution that we have for atherosclerosis.

I advocate early, aggressive, and broad screening for my patients—such as colonoscopy (or other colorectal cancer screening) at age forty, as opposed to the standard recommendation of forty-five or fifty—because the evidence is overwhelming that it’s much easier to deal with most cancers in their early stages.

Contrary to popular belief, cancer cells don’t grow faster than their noncancerous counterparts; they just don’t stop growing when they are supposed to.

The second property that defines cancer cells is their ability to travel from one part of the body to a distant site where they should not be. This is called metastasis, and it is what enables a cancerous cell in the breast to spread to the lung. This spreading is what turns a cancer from a local, manageable problem to a fatal, systemic disease.

So not only is breast cancer genetically distinct from colon cancer (as the researchers expected), but no two breast cancer tumors are very much alike.

With a few exceptions, such as glioblastoma or other aggressive brain tumors, as well as certain lung and liver cancers, solid organ tumors typically kill you only when they spread to other organs. Breast cancer kills only when it becomes metastatic. Prostate cancer kills only when it becomes metastatic. You could live without either of those organs.

Cancer spread to other, more critical organs such as the brain, the lungs, the liver, and bones. When cancer reaches those places, survival rates drop precipitously.

Cancer cells have an altered metabolism, consuming huge amounts of glucose. Second, cancer cells seem to have an uncanny ability to evade the immune system, which normally hunts down damaged and dangerous cells—such as cancerous cells—and targets them for destruction.

In the 1920s, a German physiologist named Otto Warburg discovered that cancer cells had a strangely gluttonous appetite for glucose, devouring it at up to forty times the rate of healthy tissues.

One way to locate potential tumors is by injecting the patient with radioactively labeled glucose and then doing a PET scan to see where most of the glucose is migrating. Areas with abnormally high glucose concentrations indicate the possible presence of a tumor.

I suspect that the association between obesity, diabetes, and cancer is primarily driven by inflammation and growth factors such as insulin.

Could her very strict diet, which likely inhibited her insulin and IGF-1, have played a role in her fate?

Fasting, or a fasting-like diet, increases the ability of normal cells to resist chemotherapy, while rendering cancer cells more vulnerable to the treatment.

An immunotherapy is any therapy that tries to boost or harness the patient’s immune system to fight an infection or other condition (example: vaccines). The problem with trying to treat cancer this way is that while cancer cells are abnormal and dangerous, they are technically still our cells (“self”). They have cleverly evolved to hide from the immune system and specifically our T¬†cells, the immune system’s assassins that would ordinarily kill foreign cells.

Out of dozens of different types of cancers, we have agreed-upon, reliable screening methods for only five: lung (for smokers), breast, prostate, colorectal, and cervical.

Mainstream guidelines have been waving people away from some types of early screening, such as mammography in women and blood testing for PSA, prostate-specific antigen, in men. In part this has to do with cost, and in part this has to do with the risk of false positives that may lead to unnecessary or even dangerous treatment (entailing further costs).

Medicine 2.0 says that because there are significant false positives with certain tests, we shouldn’t do these tests on most people, period.

We need to think in terms of stacking test modalities—incorporating ultrasound and MRI in addition to mammography, for example, when looking for breast cancer.

It’s no longer as simple as “Your PSA number is X or higher, and therefore we must biopsy your prostate, a painful procedure with many unpleasant possible side effects.” Now we know to look at other parameters, such as PSA velocity (the speed at which PSA has been changing over time), PSA density (PSA value normalized to the volume of the prostate gland), and free PSA (comparing the amount of PSA that is bound versus unbound to carrier proteins in the blood). When those factors are taken into account, PSA becomes a much better indicator of prostate cancer risk.

Combining these blood tests I’ve just described with the techniques of multiparametric MRI imaging means that the likelihood of performing an unnecessary biopsy or surgery is now very low.

The purpose of the colonoscopy is to look not only for full-fledged tumors but also for polyps, which are growths that form in the lining of the colon. Most polyps remain small and harmless and never become cancerous, but some have the potential to become malignant and invade the wall of the colon. Not all polyps become cancer, but all colon cancers came from polyps. This is what makes a colonoscopy such a powerful tool.

In my practice, we go further, typically encouraging average-risk individuals to get a colonoscopy by age forty—and even sooner if anything in their history suggests they may be at higher risk.

If a sessile (flat) polyp is found, for example, we’re inclined to do it sooner than if the endoscopist finds nothing at all. Two or three years might seem like a very short window of time to repeat such an involved procedure, but colon cancer has been documented to appear within the span of as little as six months to two years after a normal colonoscopy.

It remains one of the top five deadliest cancers in the United States, behind lung (#1) and breast/prostate (#2 for women/men), and just ahead of pancreas (#4) and liver (#5) cancers.

Other cancers that are relatively easy to spot on visual examination include skin cancer and melanomas. The pap smear for cervical cancer is another well-established, minimally invasive test that I recommend my patients do yearly.

we must rely on imaging technologies such as low-dose CT scans for lung cancer.

lung cancer in never-smokers ranks seventh, all by itself.

One newer technique that can enhance the ability of a screening MRI to differentiate between a cancer and noncancer is something called diffusion-weighted imaging with background subtraction, or DWI for short.

Despite all this, even something as advanced as the best DWI MRI is not without problems, if used in isolation. While the sensitivity of this test is very high (meaning it’s very good at finding cancer if cancer is there, hence very few false negatives), the specificity is relatively low (which means it’s not as good at telling you when you don’t have cancer, hence a lot of false positives).

One company leading the charge with this type of assay is called Grail, a subsidiary of the genetic-sequencing company Illumina. The Grail test, known as Galleri, looks at methylation patterns of the cell-free DNA, which are basically chemical changes to the DNA molecules that suggest the presence of cancer. Using very-high-throughput screening and a massive AI engine, the Galleri test can glean two crucial pieces of information from this sample of blood: Is cancer present? And if so, where is it? From what part of the body did it most likely originate?

The thing to keep in mind here, however, is that this test still has much higher resolution than radiographic tests such as MRI or mammogram. Those imaging-based tests require “seeing” the tumor, which can happen only when the tumor reaches a certain size.

I’m hopeful that pairing different diagnostic tests ranging from radiographic (e.g., MRI) to direct visualization (e.g., colonoscopy) to biological/genetic (e.g., liquid biopsy) will allow us to correctly identify the cancers that need treatment the soonest, with the fewest possible false positives.

The greatest obstacle to discovery is not ignorance—it is the illusion of knowledge. —DANIEL J. BOORSTIN

I always check is their APOE genotype, the gene related to Alzheimer’s disease risk

The APOE e4 allele, which is associated with a greater risk of Alzheimer’s disease—and

Alzheimer’s disease is almost twice as common in women than in men.

The more of these networks and subnetworks that we have built up over our lifetime, via education or experience, or by developing complex skills such as speaking a foreign language or playing a musical instrument, the more resistant to cognitive decline we will tend to be.

There is a parallel concept known as “movement reserve” that becomes relevant with Parkinson’s disease. People with better movement patterns, and a longer history of moving their bodies, such as trained or frequent athletes, tend to resist or slow the progression of the disease as compared to sedentary people.

Simply doing a crossword puzzle every day, on the other hand, seems only to make people better at doing crossword puzzles.

The brain is a greedy organ. It makes up just 2 percent of our body weight, yet it accounts for about 20 percent of our total energy expenditure. Its eighty-six billion neurons each have between one thousand and ten thousand synapses connecting them to other neurons or target cells,

If we lack new sources of glucose, the brain’s preferred fuel, the liver converts our fat into ketone bodies, as an alternative energy source that can sustain us for a very long time, depending on the extent of our fat stores. (Unlike muscle or liver, the brain itself does not store energy.) When our fat runs out, we will begin to consume our own muscle tissue, then our other organs, and even bone, all in order to keep the brain running at all costs. The brain is the last thing to shut off.

Insulin seems to play a key role in memory function. Insulin receptors are highly concentrated in the hippocampus, the memory center of the brain. Several studies have found that spraying insulin right into subjects’ noses—administering it as directly as possible into their brains—quickly improves cognitive performance and memory, even in people who have already been diagnosed with Alzheimer’s disease.

A woman with one copy of e4 is four times more likely to develop the disease than a man with the same genotype.

One possible recommendation for someone like her would be to switch to a Mediterranean-style diet, relying on more monounsaturated fats and fewer refined carbohydrates, in addition to regular consumption of fatty fish. There is some evidence that supplementation with the omega-3 fatty acid DHA, found in fish oil, may help maintain brain health, especially in e4/e4 carriers.

Ketogenic diet may offer a real functional advantage: when someone is in ketosis, their brain relies on a mix of ketones and glucose for fuel.

A study looking at nearly half a million patients in the United Kingdom found that grip strength, an excellent proxy for overall strength, was strongly and inversely associated with the incidence of dementia

Another somewhat surprising risk factor that has emerged is hearing loss. Studies have found that hearing loss is clearly associated with Alzheimer’s disease, but it’s not a direct symptom. Rather, it seems hearing loss may be causally linked to cognitive decline, because folks with hearing loss tend to pull back and withdraw from interactions with others. When the brain is deprived of inputs—in this case auditory inputs—it withers. Patients with hearing loss miss out on socializing, intellectual stimulation, and feeling connected;

Another surprising intervention that may help reduce systemic inflammation, and possibly Alzheimer’s disease risk, is brushing and flossing one’s teeth.

Better oral health correlates strongly with better overall health, particularly in terms of cardiovascular disease risk,

I’m not quite as confident that regular sauna use will reduce your risk of Alzheimer’s disease as I am that exercise will do so, but I am much more confident than I was at the outset of my journey. The best interpretation I can draw from the literature suggests that at least four sessions per week, of at least twenty minutes per session, at 179 degrees Fahrenheit (82¬†degrees Celsius) or hotter seems to be the sweet spot to reduce the risk of Alzheimer’s by about 65 percent (and the risk of ASCVD by 50 percent).

Other potential interventions that have shown some promise in studies include lowering homocysteine with B vitamins, while optimizing omega-3 fatty acids. Higher vitamin D levels have been correlated with better memory in e4/e4 patients but it’s difficult to know from the current literature if this means supplementing with vitamin D will reduce risk of AD. And as mentioned earlier, hormone replacement therapy for women during the transition from perimenopause to menopause seems promising, especially for women with at least one copy of e4.

Broadly, our strategy should be based on the following principles:

WHAT’S GOOD FOR THE HEART IS GOOD FOR THE BRAIN. That is, vascular health (meaning low apoB, low inflammation, and low oxidative stress) is crucial to brain health.

WHAT’S GOOD FOR THE LIVER (AND PANCREAS) IS GOOD FOR THE BRAIN. Metabolic health is crucial to brain health.

TIME IS KEY. We need to think about prevention early, and the more the deck is stacked against you genetically, the harder you need to work and the sooner you need to start. As with cardiovascular disease, we need to play a very long game.

OUR MOST POWERFUL TOOL FOR PREVENTING COGNITIVE DECLINE IS EXERCISE. We’ve talked a lot about diet and metabolism, but exercise appears to act in multiple ways (vascular, metabolic) to preserve brain health; we’ll get into more detail in Part III, but exercise—lots of it—is a foundation of our Alzheimer’s-prevention program.

Absorb what is useful, discard what is useless, and add what is specifically your own. —BRUCE LEE

Long ago, when we consumed fructose mainly in the form of fruit and honey, it enabled us to store energy as fat to survive cold winters and periods of scarcity. Fructose was our friend. Now fructose is vastly overabundant in our diet, too much of it in liquid form, which disrupts our metabolism and our overall energy balance. We can easily take in far more fructose calories than our bodies can safely handle.

This new environment we have created is potentially toxic with respect to what we eat (chronically, not acutely), how we move (or don’t move), how we sleep (or don’t sleep), and its overall effect on our emotional health (just spend a few hours on social media).

Exercise is not just one thing, so I break it down into its components of aerobic efficiency, maximum aerobic output (VO2 max), strength, and stability,

I will not be talking much about exogenous molecules, beyond those that I have already mentioned specifically (e.g., lipid-lowering drugs, rapamycin, and metformin, the diabetes drug that is being tested for possible longevity effects).

The example of car accidents, which also happen to be a minor obsession of mine. They kill far too many people across all age groups—one person every twelve minutes, according to the National Highway Traffic Safety Administration—yet

What can we do to reduce our risk of dying behind the wheel? Is it even possible to avoid car accidents, when they seem so random? The obvious tactics we already know about: wear a seat belt, don’t text and drive (seemingly difficult for many people), and don’t drink and drive, since alcohol is a factor in up to a third of fatalities. Automotive fatality statistics also reveal that almost 30 percent of deaths involve excessive speed.

I had almost automatically assumed that freeways would prove to be the deadliest place to drive because of the high speeds involved. But decades’ worth of auto accident data reveal that, in fact, a very high proportion of fatalities occur at intersections. The most common way to be killed, as a driver, is by another car that hits yours from the left, on the driver’s side, having run a red light or traveling at high speed.

Before entering any intersection, even if he has the right of way (i.e., a green light), he always looks left first, then right, specifically to avoid this type of crash.

Our tactic has leverage: a relatively minor effort yields a potentially significant risk reduction.

We approach our tactics the same way, zooming in from the vague and general to the specific and targeted. We use data and intuition to figure out where to focus our efforts, and feedback to determine what is and isn’t working. And seemingly small tweaks can yield a significant advantage if compounded over time.

When I evaluate new patients, I’m always asking three key questions: a. ¬†Are they overnourished or undernourished? That is, are they taking in too many or too few calories? b. ¬†Are they undermuscled or adequately muscled? c. ¬†Are they metabolically healthy or not?

For example, with a patient who is overnourished, we want to find a way to reduce their caloric intake (there are three ways to do this, as you’ll see in chapter 15). But if they are also undermuscled, which is common, we want to be careful to make sure they are still getting enough protein, since the goal is not weight loss but fat loss coupled with muscle gain.

We rely heavily on data in our decision-making and developing our tactics, including static biomarkers such as triglycerides and liver function tests, as well as dynamic biomarkers such as oral glucose tolerance tests, along with anthropometric measures such as data on body composition, visceral adipose tissue, bone density, and lean mass.

I used to recommend long periods of water-only fasting for some of my patients—and practiced it myself. But I no longer do so, because I’ve become convinced that the drawbacks (mostly having to do with muscle loss and undernourishment) outweigh its metabolic benefits in all but my most overnourished patients.

There are reams of data supporting the notion that even a fairly minimal amount of exercise can lengthen your life by several years. It delays the onset of chronic diseases, pretty much across the board, but it is also amazingly effective at extending and improving healthspan. Not only does it reverse physical decline, which I suppose is somewhat obvious, but it can slow or reverse cognitive decline as well.

Going from zero weekly exercise to just ninety minutes per week can reduce your risk of dying from all causes by 14¬†percent. It’s very hard to find a drug that can do that.

For those who are not habitual exercisers (yet), you’re in luck: The benefits of exercise begin with any amount of activity north of zero—even brisk walking—and go up from there. Just as almost any diet represents a vast improvement over eating only fast food, almost any exercise is better than remaining sedentary.

Let’s start with cardiorespiratory or aerobic fitness. This means how efficiently your body can deliver oxygen to your muscles, and how efficiently your muscles can extract that oxygen, enabling you to run (or walk) or cycle or swim long distances. It also comes into play in daily life, manifesting as physical stamina.

VO2 max represents the maximum rate at which a person can utilize oxygen. This is measured, naturally, while a person is exercising at essentially their upper limit of effort.

The fitter I am, the more oxygen I can consume to make ATP,

An average forty-five-year-old man will have a VO2 max around 40 ml/kg/min, while an elite endurance athlete will likely score in the high 60s and above. An unfit person in their thirties or forties, on the other hand, might score only in the high 20s on a VO2 max test,

A person who smokes has a 40 percent greater risk of all-cause mortality (that is, risk of dying at any moment) than someone who does not smoke, representing a hazard ratio or (HR) of 1.40. This study found that someone of below-average VO2 max for their age and sex (that is, between the 25th and 50th percentiles) is at double the risk of all-cause mortality compared to someone in the top quartile (75th to 97.6th percentiles). Thus, poor cardiorespiratory fitness carries a greater relative risk of death than smoking.

Someone in the least fit 20 percent has a 4.09 times greater risk of dying than a person in the top 2 percent of their age and sex category.

at least five factors[*3] increase my confidence in at least the partial causality of this relationship. First, the magnitude of the effect size is very large. Second, the data are consistent and reproducible across many studies of disparate populations. Third, there is a dose-dependent response (the fitter you are, the longer you live). Fourth, there is great biologic plausibility to this effect, via the known mechanisms of action of exercise on lifespan and healthspan. And fifth, virtually all experimental data on exercise in humans suggest that it supports improved health.

As the authors of the JAMA study concluded, “Cardiorespiratory fitness is inversely associated with long-term mortality with no observed upper limit of benefit

A ten-year observational study of roughly 4,500 subjects ages fifty and older found that those with low muscle mass were at 40 to 50 percent greater risk of mortality than controls, over the study period. Further analysis revealed that it’s not the mere muscle mass that matters but the strength of those muscles, their ability to generate force.

John Ioannidis, a Stanford scientist with a penchant for asking provocative questions, decided to test this metaphor literally, running a side-by-side comparison of exercise studies versus drug studies. He found that in numerous randomized clinical trials, exercise-based interventions performed as well as or better than multiple classes of pharmaceutical drugs at reducing mortality from coronary heart disease,[*5] prediabetes or diabetes, and stroke.

By age eighty, the average person will have lost eight kilograms of muscle, or about eighteen pounds, from their peak. But people who maintain higher activity levels lose much less muscle, more like three to four kilograms on average.

Your exoskeleton (muscle) is what keeps your actual skeleton (bones) upright and intact.

It is highly correlated with a lower risk of falling, a leading but oft-ignored cause of death and disability in the elderly.

I was a one-dimensional athlete, and if I had kept it up, I might have ended up with my spine fused into my time-trial tuck, still able to ride my bike but unable to do anything else useful, especially with my upper body.

Of all Olympic athletes, the decathletes are most revered.

They are not the best at any of the ten individual events in which they compete; they likely would not even medal. But they are still considered the greatest because they are remarkably good at so many different events. They are true generalists—yet they train like specialists.

Think of the Centenarian Decathlon as the ten most important physical tasks you will want to be able to do for the rest of your life.

I start by presenting my patients with a long list of physical tasks that might include some of the following: Hike 1.5 miles on a hilly trail. Get up off the floor under your own power, using a maximum of one arm for support. Pick up a young child from the floor. Carry two five-pound bags of groceries for five blocks. Lift a twenty-pound suitcase into the overhead compartment of a plane. Balance on one leg for thirty seconds, eyes open. (Bonus points: eyes closed, fifteen seconds.) Have sex. Climb four flights of stairs in three minutes. Open a jar. Do thirty consecutive jump-rope skips.

If you want to pick up that thirty-pound grandkid or great-grandkid when you’re eighty, you’re going to have to be able to lift about fifty to fifty-five pounds now. Without hurting yourself. Can you do that?

You also want to be able to hike on a hilly trail? To do that comfortably requires a VO2 max of roughly 30 ml/kg/min. Let’s take a look at the results of your latest VO2 max test—and guess what, you only scored a 30. You’re average for your age, but I’m afraid that’s not good enough, because your VO2 max is also going to decline.

To lift that twenty-pound suitcase overhead when you are older means doing so with forty or fifty pounds now. To be able to climb four flights of stairs in your eighties means you should be able to pretty much sprint up those same stairs today. In every case, you need to be doing much more now, to armor yourself against the natural and precipitous decline in strength and aerobic capacity that you will undergo as you age.

My version of the Decathlon is tailored to my own particular interests, such as swimming and archery. It’s also fairly aggressive, I admit, reflecting the importance of a high level of fitness in my life. So I would probably add in some of the following events: Swim half a mile in twenty minutes. Walk with a thirty-pound dumbbell in each hand for one minute. Draw back and fire a fifty-pound compound bow. Do five pull-ups. Climb ninety steps in two minutes (VO2 max = 32). Dead-hang for one minute. Drive a race car within 5 to 8 percent of the pace I can do so today. Hike with a twenty-pound backpack for an hour. Carry my own luggage. Walk up a steep hill.

The old-school fitness guru Jack LaLanne, who kept doing his usual rigorous daily workout right up until his death at age ninety-six.

We must stop pointlessly “exercising,” just because we think we are supposed to, banging away on the elliptical trainer at lunch hour. I promise, you can do better. I suggest you join me and start training, with a very specific purpose, which is to be kick-ass one-hundred-year-olds.

We are interested in two particular regions of this continuum: long, steady endurance work, such as jogging or cycling or swimming, where we are training in what physiologists call zone 2, and maximal aerobic efforts, where VO2 max comes into play.

If you use your muscles to counter some resistance, in the form of weights or other forces (e.g., gravity, or elastic bands), they will adapt and grow stronger.

Zone 2 is more or less the same in all training models: going at a speed slow enough that one can still maintain a conversation but fast enough that the conversation might be a little strained. It translates to aerobic activity at a pace somewhere between easy and moderate.

Our mitochondria can convert both glucose and fatty acids to energy—but while glucose can be metabolized in multiple different ways, fatty acids can be converted to energy only in the mitochondria.

Aerobic exercise, done in a very specific way, improves our ability to utilize glucose and especially fat as fuel.

The healthier and more efficient your mitochondria, the greater your ability to utilize fat, which is by far the body’s most efficient and abundant fuel source.

The professional cyclists could zoom along, producing a huge amount of power while still burning primarily fat. But the subjects with metabolic syndrome relied almost entirely on glucose for their fuel source, even from the first pedal stroke. They had virtually zero ability to tap into their fat stores, meaning they were metabolically inflexible: able to use only glucose but not fat.

A professional rider’s zone 2 output feels like zone 5 for most people.)

When we are exercising in zone 2, most of the work is being done by our type 1, or “slow-twitch,” muscle fibers. These are extremely dense with mitochondria and thus well-suited for slow-paced, efficient endurance work.

If we pick up the pace, we begin to recruit more type 2 (“fast-twitch”) muscle fibers, which are less efficient but more forceful. They also generate more lactate in the process, because of the way they create ATP. Lactate itself is not bad; trained athletes are able to recycle it as a type of fuel. The problem is that lactate becomes lactic acid when paired with hydrogen ions, which is what causes that acute burning you feel in your muscles[*1] during a hard effort.

In technical terms, San Mill√°n describes zone 2 as the maximum level of effort that we can maintain without accumulating lactate. We still produce it, but we’re able to match production with clearance.

I often test my own lactate while I am working out this way, using a small handheld lactate monitor, to make sure my pacing is correct. The goal is to keep lactate levels constant, ideally between 1.7 and 2.0 millimoles.

If you know your maximum heart rate—not estimated, but your actual maximum, the highest number you’ve ever seen on a heart rate monitor—your zone 2 will correspond to between approximately 70 and 85¬†percent of that peak number, depending on your fitness levels. That’s a big range, so when starting people out, I prefer they rely on their rate of perceived exertion, or RPE, also known as the “talk test.” How hard are you working? How easy is it to speak? If you’re at the top of zone 2, you should be able to talk but not particularly interested in holding a conversation.

They very quickly switched over from aerobic respiration, burning fat and glucose in the mitochondria with oxygen, to the much less efficient glycolysis, an energy-producing pathway that consumes only glucose and produces loads of lactate (similar to the way cancer cells produce energy, via the Warburg effect).

People with obesity or other metabolic problems will tend to have much higher resting lactate levels, a clear sign that their mitochondria are not functioning optimally, because they are already working too hard just to maintain baseline energy levels. This means that they are relying almost totally on glucose (or glycogen) for all their energy needs—and that they are totally unable to access their fat stores.

Mitochondria are incredibly plastic, and when we do aerobic exercise, it stimulates the creation of many new and more efficient mitochondria through a process called mitochondrial biogenesis, while eliminating ones that have become dysfunctional via a recycling process called mitophagy (which is like autophagy,

Muscle is the largest glycogen storage sink in the body, and as we create more mitochondria, we greatly increase our capacity for disposing of that stored fuel, rather than having it end up as fat or remaining in our plasma. Chronic blood glucose elevations damage organs from our heart to our brain to our kidneys and nearly everything in between—even contributing to erectile dysfunction in men.

Studies have found that while we are exercising, our overall glucose uptake increases as much as one-hundred-fold compared to when we are at rest. What’s interesting is that this glucose uptake occurs via multiple pathways. There is the usual, insulin-signaled way that we’re familiar with, but exercise also activates other pathways, including one called non-insulin-mediated glucose uptake, or NIMGU, where glucose is transported directly across the cell membrane without insulin being involved at all.

This in turn explains why exercise, especially in zone 2, can be so effective in managing both type 1 and type 2 diabetes: It enables the body to essentially bypass insulin resistance in the muscles to draw down blood glucose levels.

I have one patient with type 1 diabetes, meaning he produces zero insulin, who keeps his glucose in check almost entirely by walking briskly for six to ten miles every day, and sometimes more. As he walks, his muscle cells are vacuuming glucose out of his bloodstream via NIMGU. He still needs to inject himself with insulin, but only a tiny fraction of the amount that he would otherwise require.

It seems that about three hours per week of zone 2, or four 45-minute sessions, is the minimum required for most people to derive a benefit and make improvements,

Four times a week, I will spend about an hour riding my stationary bike at my zone 2 threshold.

One way to track your progression in zone 2 is to measure your output in watts at this level of intensity. (Many stationary bikes can measure your wattage as you ride.) You take your average wattage output for a zone 2 session and divide it by your weight to get your watts per kilogram, which is the number we care about. So if you weigh 60 kilos (about 132 pounds) and can generate 125 watts in zone 2, that works out to a bit more than 2 watts/kg, which is about what one would expect from a reasonably fit person. These are rough benchmarks, but someone who is very fit will be able to produce 3 watts/kg, while professional cyclists put out 4 watts/kg and up.

Zone 2 can be a bit boring on its own, so I typically use the time to listen to podcasts or audiobooks,

At VO2 max, we are using a combination of aerobic and anaerobic pathways to produce energy, but we are at our maximum rate of oxygen consumption.

The VO2 max test is an unpleasant affair that entails riding an exercise bike or running on a treadmill at ever greater intensity, while wearing a mask designed to measure oxygen consumption and CO2 production.

A thirty-five-year-old man with average fitness for his age—a VO2 max in the mid-30s—should be able to run at a ten-minute mile pace (6¬†mph). But by age seventy, only the very fittest 5 percent of people will still be able to manage this.

Studies suggest that your VO2 max will decline by roughly 10 percent per decade—and up to 15¬†percent per decade after the age of fifty.

The more active you want or plan to be as you age, the more you need to train for it now.

Improving your VO2 max from the very bottom quartile to the quartile above (i.e., below average) is associated with almost a 50 percent reduction in all-cause mortality,

Once maximal oxygen consumption or VO2 max drops below a certain level (typically about 18 ml/kg/min in men, and 15 in women), it begins to threaten your ability to live on your own.

One study found that boosting elderly subjects’ VO2 max by 6 ml/kg/min, or about 25 percent, was equivalent to subtracting twelve years from their age.

The beauty of this is that VO2 max can always be improved by training, no matter how old you are. Don’t believe me? Then let me introduce you to an amazing Frenchman named Robert Marchand, who set an age-group world record in 2012 by cycling 24.25 kilometers in an hour, at the age of 101.

The tried-and-true formula for these intervals is to go four minutes at the maximum pace you can sustain for this amount of time—not an all-out sprint, but still a very hard effort. Then ride or jog four minutes easy, which should be enough time for your heart rate to come back down to below about one hundred beats per minute. Repeat this four to six times and cool down.

A single workout per week in this zone will generally suffice.

Hunting requires 95 percent slow and steady effort, and 5 percent all-out intensity.

Muscle mass begins to decline as early as our thirties.

We lose muscle strength about two to three times more quickly than we lose muscle mass. And we lose power (strength x speed) two to three times faster than we lose strength. This is because the biggest single change in the aging muscle is the atrophy of our fast twitch or type 2 muscle fibers.

It is very difficult to put on muscle mass later in life.

Another metric that we track closely in our patients is their bone density (technically, bone mineral density or BMD).

Another metric that we track closely in our patients is their bone density (technically, bone mineral density or BMD). We measure BMD in every patient, every year, looking at both of their hips and their lumbar spine using DEXA. This also measures body fat and lean mass, so it’s a useful tool across all of the body-composition domains that we care about.

The fact is that bone density diminishes on a parallel trajectory to muscle mass, peaking as early as our late twenties before beginning a slow, steady decline.

The mortality from a hip or femur fracture is staggering once you hit about the age of sixty-five. It varies by study, but ranges from 15 to 36¬†percent in one year—meaning that up to one-third of people over sixty-five¬†who fracture their hip are dead within a year. Even if a person does not die from the injury, the setback can be the functional equivalent of death in terms of how much muscle mass and, hence, physical capacity is lost during the period of bed rest

You should at least check your BMD every few years. (Particularly if your primary sports are nonweight-bearing, like cycling or swimming.)

I think of strength training as a form of retirement saving. Just as we want to retire with enough money saved up to sustain us for the rest of our lives, we want to reach older age with enough of a “reserve” of muscle (and bone density) to protect us from injury and allow us to continue to pursue the activities that we enjoy.

Carrying is our superpower as a species. It’s one reason why we have thumbs, as well as long legs (and arms). No other animal is capable of carrying large objects from one place to another with any efficiency.

I’ve also become semiobsessed with an activity called rucking, which basically means hiking or walking at a fast pace with a loaded pack on your back. Three or four days a week, I’ll spend an hour rucking around my neighborhood, up and down hills, typically climbing and descending several hundred feet over the course of three or four miles. The fifty- to sixty-pound pack on my back makes it quite challenging, so I’m strengthening my legs and my trunk while also getting in a solid cardiovascular session. The best part is that I never take my phone on these outings; it’s just me, in nature, or maybe with a friend or a family member or a houseguest

Michael Easter in his eye-opening book The Comfort Crisis.

(A good goal is to be able to carry one-quarter to one-third of your body weight once you develop enough strength and stamina.

Fundamentally I structure my training around exercises that improve the following: Grip strength,

Attention to both concentric and eccentric loading for all movements, meaning when our muscles are shortening (concentric) and when they are lengthening (eccentric).

Pulling motions, at all angles from overhead to in front of you,

Hip-hinging movements, such as the deadlift and squat, but also step-ups, hip-thrusters, and countless single-leg variants of exercises that strengthen the legs, glutes, and lower back.

Our grip is our primary point of contact in almost any physical task, from swinging a golf club to chopping wood; it is our interface with the world. If our grip is weak, then everything else is compromised.

One of my favorite ways to do it is the classic farmer’s carry, where you walk for a minute or so with a loaded hex bar or a dumbbell or kettlebell in each hand. (Bonus points: Hold the kettlebell up vertically, keeping your wrist perfectly straight and elbow cocked at ninety degrees, as though you were carrying it through a crowded room.) One of the standards we ask of our male patients is that they can carry half their body weight in each hand (so full body weight in total) for at least one minute, and for our female patients we push for 75 percent of that weight.

Another way to test your grip is by dead-hanging from a pull-up bar for as long as you can.

Here we like to see men hang for at least two minutes and women for at least ninety seconds at the age of forty.

Eccentric loading means loading the muscle as it is lengthening, such as when you lower a bicep curl. It’s more intuitive when lifting something to focus on the concentric phase, such as curling the dumbbell with your biceps. This is the strength of a muscle getting shorter. One of the tests we have our patients perform is stepping onto and off an eighteen-inch block and taking three full seconds to reach the ground (a forward step down, like descending a very tall step).

we have our patients work up to weighted hip-hinging very slowly, typically beginning with single-leg step-ups (see description below) and split-stance Romanian deadlift,

all the aerobic fitness or strength in the world won’t help you if you get hurt and have to stop exercising for several months—or forever.

stability is the subconscious ability to harness, decelerate, or stop force.

in the exercise context, we’re not as interested in how rigid something is. Instead, we want to think about how efficiently and safely force can be transmitted through something.

Beth Lewis, a former professional dancer and powerlifter turned trainer and all-around movement genius

Short for dynamic neuromuscular stabilization,

DNS. Short for dynamic neuromuscular stabilization,

Michael Stromsness,

I suggest visiting the websites for DNS (www.rehabps.com) and the Postural Restoration Institute (PRI) (www.posturalrestoration.com)

Stability training begins at the most basic level, with the breath.

In one experiment, researchers found that combining a breathing challenge (reducing the amount of oxygen available to study subjects) with a weight challenge reduced the subjects’ ability to stabilize their spine.

One simple test that we ask of everyone, early on, looks like this: lie on your back, with one hand on your belly and the other on your chest, and just breathe normally, without putting any effort or thought into it. Notice which hand is rising and falling—is it the one on your chest, or your belly, or both (or neither)?

HYPERINFLATED. This person is an upper-chest breather who tends to pull up into spinal extension for both respiration and stability. Their lumbar spine is in hyperextension, while their pelvis lives in anterior (forward) tilt, meaning their butt sticks out.

COMPRESSED. Everything about them is sort of scrunched down and tight. Their head juts forward, and so do their shoulders, which kind of roll to the front because they are always pulling forward to try and take in more air. Their midback rolls in an overly flexed or hyperkyphotic posture, and they have limited neck and upper limb motion.

COMPRESSED. Everything about them is sort of scrunched down and tight. Their head juts forward, and so do their shoulders, which kind of roll to the front because they are always pulling forward to try and take in more air. Their midback rolls in an overly flexed or hyperkyphotic posture, and they have limited neck and upper limb motion. Sometimes their lower legs externally rotate, and the feet overpronate. Gravity is weighing them down.

UNCONTROLLED. These folks have extreme passive range of motion (i.e., flexibility)—and extremely limited ability to control it. They can often do a toe touch and put their palms flat on the floor, but because of their lack of control, these people are quite prone to joint injuries.

She has the patient lie on their back with legs up on a bench or chair, and asks them to inhale as quietly as possible, with the least amount of movement possible. An ideal inhalation expands the entire rib cage—front, sides, and back—while the belly expands at the same time, allowing the respiratory and pelvic diaphragm to descend. The telltale is that it is quiet. A noisy inhale looks and feels more dramatic, as the neck, chest, or belly will move first, and the diaphragm cannot descend freely, making it more difficult to get air in. Now, exhale fully through pursed lips for maximum compression and air resistance, to strengthen the diaphragm. Blow all that air out, fully emptying yourself before your shoulders round or your face or jaw gets tense. Very soon, you will see how a full exhale prepares you for a good inhale, and vice versa. Repeat the process for five breaths and do two to three sets. Be sure to pause after each exhale for at least two counts to hold the isometric contraction—this is key, in DNS.

In DNS, you learn to think of the abdomen as a cylinder, surrounded by a wall of muscle, with the diaphragm on top and the pelvic floor below. When the cylinder is inflated, what you’re feeling is called intra-abdominal pressure, or IAP.

breathe all the way in, so you feel as if you are inflating the cylinder on all sides and pulling air all the way down into your pelvic floor, the bottom of the cylinder. You’re not actually “breathing” there, in the sense that air is actually entering your pelvis; you’re seeking maximal lung expansion, which in turn sort of pushes your diaphragm down. With every inhale, focus on expanding the cylinder around its whole diameter and not merely raising the belly. If you do this correctly, you will feel the entire circumference of your shorts expand evenly around your waist, even in the back, not just in the front. When you exhale, the diaphragm comes back up, and the ribs should rotate inward again as your waistband contracts.

I practice this 360-degree abdominal breathing every day, not only in the gym but also while I am at my desk.

Our feet are literally the foundation for any movement we might make. Whether we’re lifting something heavy, walking or running (or rucking), climbing stairs, or standing waiting for a bus, we’re always channeling force through our feet.

Toe yoga is a lot harder than it sounds, which is why I’ve posted a video demonstration of this and other exercises at www.peterattiamd.com/‚Äãoutlive/‚Äãvideos.

Toe strength may not be something you think about when you go to the gym, but it should be: Our toes are crucial to walking, running, lifting, and, most importantly, decelerating or lowering. The big toe especially is necessary for the push-off in every stride.

Try to lift all ten toes off the ground and spread them as wide as you can. Now try to put just your big toe back on the floor, while keeping your other toes lifted.

Now do the opposite: keep four toes on the floor and lift only your big toe. Then lift all five toes, and try to drop them one by one, starting with your big toe.

when I squat, or do any standing lift, my first step is to ground my feet, to be aware of all four “corners,” and distribute weight equally.

stand with one foot in front of the other and try to balance. Now close your eyes and see how long you can hold the position. Ten seconds is a respectable time; in fact, the ability to balance on one leg at ages fifty and older has been correlated with future longevity, just like grip strength.

The spine has three parts: lumbar (lower back), thoracic (midback), and cervical (neck) spine.

Get on your hands and knees and go through an extremely slowed-down, controlled Cat/Cow sequence, similar to the basic yoga poses of the same names.[*4] The difference is that you have to really, really slow down, moving so slowly and deliberately from one end of your spine to the other that you can feel each individual vertebra changing position, all the way from your tailbone up to your neck, until your spine is bent like a sway-backed cow. Then reverse the movement, tilting your pelvis forward and bending your spine one vertebra at a time until your back is arched again, like a really scared cat. (Note: Inhale on Cow, exhale on Cat.)

Beth taught me a simple exercise to help understand the importance of scapular positioning and control, a movement known as Scapular CARs, for controlled articular rotations: Stand with your feet shoulder-width apart and place a medium to light resistance band under your feet, one handle in each hand (a very light dumbbell also works). Keeping your arms at your sides, raise your shoulder blades, and then squeeze them back and together; this is retraction, which is where we want them to be when under load. Then drop them down your back. Finally, bring them forward to the starting point. We start out moving in squares like this, but the goal is to learn enough control that we can move our scapulae in smooth circles.

I would urge you to film yourself working out from time to time, to compare what you think you are doing to what you are actually doing with your body.

“If you’re not pushing ahead, you’re going backwards.”

Diet and nutrition are so poorly understood by science, so emotionally loaded, and so muddled by lousy information and lazy thinking that it is impossible to speak about them in nuanced terms at a party or, say, on social media.

The correlation between poor metabolic health and being overnourished and undermuscled is very high.

Nutrition is relatively simple, actually. It boils down to a few basic rules: don’t eat too many calories, or too few; consume sufficient protein and essential fats; obtain the vitamins and minerals you need; and avoid pathogens like E. coli and toxins like mercury or lead.

In epidemiology, researchers gather data on the habits of large groups of people, looking for meaningful associations or correlations with outcomes

The problem is that epidemiology is incapable of distinguishing between correlation and causation.

The point is that humans are terrible study subjects for nutrition (or just about anything else) because we are unruly, disobedient, messy, forgetful, confounding, hungry, and complicated creatures.

This is also known as healthy user bias, meaning that study results sometimes reflect the baseline health of the subjects more than the influence of whatever input is being studied—as

The people who are still drinking in older age tend to do so because they are healthy, and not the other way around.

The authors concluded that there is no dose of alcohol that is “healthy.”

Clinical trials would seem like a much better way to evaluate one diet against another: One group of subjects eats diet X, the other group is on diet Y, and you compare the results.

There’s a trade-off between sample size, study duration, and control. To do a long study in a large group of subjects, you essentially have to trust that they are following the prescribed diet,

I’m convinced that compliance is the key issue in nutrition research, and with diets in general: Can you stick to it? The answer is different for almost everyone.

Efficacy tests how well the intervention works under perfect conditions and adherence (i.e., if one does everything exactly as prescribed). Effectiveness tests how well the intervention works under real-world conditions, in real people.

While I was technically following a virtuous “vegan” diet, I was basically eating a bunch of junk food that just didn’t happen to contain animal products. In other words, I was on a vegan version of the SAD, the Standard American Diet.

It is our default food environment, occupying the middle of the grocery store: the boxed and frozen and bagged bounty of an agricultural system that produces subsidized corn, flour, sugar, and soybeans by the megaton. On one level, it’s brilliant, a solution to four problems that have plagued humanity since the beginning: (1) how to produce enough food to feed almost everyone; (2) how to do so inexpensively; (3) how to preserve that food so it can be stored and transported safely; and (4) how to make it highly palatable. If you optimize for all four of these characteristics, you’re pretty much guaranteed to end up with the SAD, which is not so much a diet as a business model for how to feed the world efficiently. Two cheers for modern industrial food systems. But notice that a fifth criterion is missing: how to make it harmless.

The elements that constitute the SAD are almost as devastating to most people as tobacco when consumed in large quantities, as intended: added sugar, highly refined carbohydrates with low fiber content, processed oils, and other very densely caloric foods.

The farther away we get from the SAD, the better off we will be. This is the common goal of most “diets”—to help us break free of the powerful gravitational pull of the SAD so that we can eat less, and hopefully eat better.

Three strategies to accomplish this: CALORIC RESTRICTION, or CR: eating less in total, but without attention to what is being eaten or when it’s being eaten DIETARY RESTRICTION, or DR: eating less of some particular element(s) within the diet (e.g., meat, sugar, fats) TIME RESTRICTION, or TR: restricting eating to certain times, up to and including multiday fasting

Many of the problems we want to address or avoid stem from consuming calories in excess of what we can use or safely store. If we take in more energy than we require, the surplus ends up in our adipose tissue, one way or another. If this imbalance continues, we exceed the capacity of our “safe” subcutaneous fat tissue, and excess fat spills over into our liver, our viscera, and our muscles,

There is plenty of research showing that people who count their calories and limit them can and do lose weight,

Deep caloric restriction may confer is worth some of the trade-offs—including potentially weakened immunity and greater susceptibility to cachexia and sarcopenia (muscle loss), not to mention constant hunger.

Any form of DR that restricts protein, for example, is probably a bad idea for most people, because it likely also impairs the maintenance or growth of muscle. Similarly, replacing carbohydrates with lots of saturated fats can backfire if it sends your apoB concentration (and thus your cardiovascular disease risk) sky-high.

A ketogenic diet means restricting carbohydrates to such an extent that the body begins metabolizing fat into “ketone bodies” that the muscles and brain can utilize as fuel.

Alcohol should be considered as its own category of macronutrient because it is so widely consumed, it has such potent effects on our metabolism, and it is so calorically dense at 7 kcal/g (closer to the 9 kcal/g of fat than the 4 kcal/g of both protein and carbohydrate). Alcohol serves no nutritional or health purpose but is a purely hedonic pleasure that needs to be managed. It’s especially disruptive for people who are overnourished, for three reasons: it’s an “empty” calorie source that offers zero nutrition value; the oxidation of ethanol delays fat oxidation, which is the exact opposite of what we want if we’re trying to lose fat mass; and drinking alcohol very often leads to mindless eating.

Ethanol is a potent carcinogen, and chronic drinking has strong associations with Alzheimer’s disease, mainly via its negative effect on sleep, but possibly via additional mechanisms. Like fructose, alcohol is preferentially metabolized in the liver, with well-known long-term consequences in those who drink to excess. Last, it loosens inhibitions around other kinds of food consumption;

I strongly urge my patients to limit alcohol to fewer than seven servings per week, and ideally no more than two on any given day,

Carbohydrates are our primary energy source. In digestion, most carbohydrates are broken down to glucose, which is consumed by all cells to create energy in the form of ATP. Excess glucose, beyond what we need immediately, can be stored in the liver or muscles as glycogen for near-term use or socked away in adipose tissue (or other places) as fat. This decision is made with the help of the hormone insulin, which surges in response to the increase in blood glucose.

Continuous glucose monitoring, or CGM,

The device consists of a microscopic filament sensor that is implanted in the upper arm, attached to a fingertip-sized transmitter that sends data to the patient’s phone in real time.

The power of CGM is that it enables us to view a person’s response to carbohydrate consumption in real time and make changes rapidly to flatten the curve and lower the average.

Typically, my healthy patients need to use CGM only for a month or two before they begin to understand what foods are spiking their glucose (and insulin) and how to adjust their eating pattern to obtain a more stable glucose curve. Once they have this knowledge, many of them no longer need CGM. It’s a worthwhile investment.

We want to lower average blood glucose and reduce the amount of variability from day to day and hour to hour.

I’ve found that CGM powerfully activates the Hawthorne effect, the long-observed phenomenon whereby people modify their behavior when they are being watched.

I like to keep average glucose at or below 100 mg/dL, with a standard deviation of less than 15 mg/dL.

“healthy” meals, for example certain kinds of vegetarian tacos, can also send glucose levels soaring in some people but not others. It also depends on when those carbs are eaten.

Everyone tends to be more insulin sensitive in the morning than in the evening, so it makes sense to front-load our carb consumption earlier in the day.

It still amazes me how much even one night of horrible sleep cripples our ability to dispose of glucose the next day.

Stress prompts an elevation in cortisol, which in turn stimulates the liver to drip more glucose into circulation.

Not all carbs are created equal. The more refined the carb (think dinner roll, potato chips), the faster and higher the glucose spike. Less processed carbohydrates and those with more fiber, on the other hand, blunt the glucose impact. I try to eat more than fifty grams of fiber per day.

Rice and oatmeal are surprisingly glycemic (meaning they cause a sharp rise in glucose levels), despite not being particularly refined; more surprising is that brown rice is only slightly less glycemic than long-grain white rice.

Fructose-heavy foods will still likely cause blood-glucose spikes.

Aerobic exercise seems most efficacious at removing glucose from circulation, while high-intensity exercise and strength training tend to increase glucose transiently, because the liver is sending more glucose into the circulation to fuel the muscles. Don’t be alarmed by glucose spikes when you are exercising.

Nonstarchy veggies such as spinach or broccoli have virtually no impact on blood sugar.

Foods high in protein and fat (e.g., eggs, beef short ribs) have virtually no effect on blood sugar

If you’re stressed out, sleeping poorly, and unable to make time to exercise, be as careful as possible with what you eat.

Unlike carbs and fat, protein is not a primary source of energy. We do not rely on it in order to make ATP, nor do we store it the way we store fat (in fat cells) or glucose (as glycogen). If you consume more protein than you can synthesize into lean mass, you will simply excrete the excess in your urine as urea.

We must obtain nine of the twenty amino acids that we require from our diet, because we can’t synthesize them.

In my patients I typically set 1.6 g/kg/day as the minimum, which is twice the RDA. The ideal amount can vary from person to person, but the data suggest that for active people with normal kidney function, one gram per pound of body weight per day (or 2.2 g/kg/day) is a good place to start—nearly triple the minimal recommendation.

It should not be taken in one sitting but rather spread out over the day to avoid losing amino acids to oxidation (i.e., using them to produce energy when we want them to be available for muscle protein synthesis). The literature suggests that the ideal way to achieve this is by consuming four servings of protein per day, each at ~0.25 g/lb of body weight. A six-ounce serving of chicken, fish, or meat will provide about 40 to 45 grams (at about 7 grams of actual protein per ounce of meat),

Typically, I will consume a protein shake, a high-protein snack, and two protein meals.)

If you choose to get all your protein from plants, you need to understand two things. First, the protein found in plants is there for the benefit of the plant, which means it is largely tied up in indigestible fiber, and therefore less bioavailable to the person eating it.

Some of this can be overcome by cooking the plants, but that still leaves us with the second issue. The distribution of amino acids is not the same as in animal protein. In particular, plant protein has less of the essential amino acids methionine, lysine, and tryptophan, potentially leading to reduced protein synthesis.

The same is true of protein supplements. Whey protein isolate (from dairy) is richer in available amino acids than soy protein isolate.

Focus on the absolute amount of these amino acids found in each meal, and be sure to get about three to four grams per day of leucine and lycine and at least one gram per day of methionine for maintenance of lean mass. If you are trying to increase lean mass, you’ll need even more leucine, closer to two to three grams per serving, four times per day.

Eating protein also helps us feel satiated, inhibiting the release of the hunger-inducing hormone ghrelin, so we eat fewer calories overall.

Fats have long had a bad rap, on two counts: their high caloric content (9 kcal/g) and their role in raising LDL cholesterol and thus heart disease risk.

While carbohydrates are primarily a source of fuel and amino acids are primarily building blocks, fats are both. They are very efficient fuel for oxidation (think: slow-burning logs) and also the building blocks for many of our hormones (in the form of cholesterol) and cell membranes. Eating the right mix of fats can help maintain metabolic balance, but it is also important for the health of our brain, much of which is composed of fatty acids. On a practical level, dietary fat also tends to leave one feeling more satiated than many types of carbohydrates, especially when combined with protein.

There are (broadly) three types of fats: saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA).[*9] The differences between these have to do with differences in their chemical structure; a “saturated” fat simply has more hydrogen atoms attached to its carbon chain.[*10] Within PUFA, we make one more important distinction, which is to separate the omega-6 from the omega-3 variants

We can further subdivide omega-3 PUFA into marine (EPA, DHA) and nonmarine sources (ALA). Salmon and other oil-rich seafood provide the former, nuts and flaxseed the latter.

We try to boost MUFA closer to 50—55 percent, while cutting SFA down to 15—20 percent and adjusting total PUFA to fill the gap. We also boost EPA and DHA, those fatty acids that are likely important to brain and cardiovascular health, with marine fat sources and/or supplementation.

Eating more olive oil and avocados and nuts, cutting back on (but not necessarily eliminating) things like butter and lard, and reducing the omega-6-rich corn, soybean, and sunflower oils—while also looking for ways to increase high-omega-3 marine PUFAs from sources such as salmon and anchovies.

Finally, unless they are eating a lot of fatty fish, filling their coffers with marine omega-3 PUFA, they almost always need to take EPA and DHA supplements in capsule or oil form.

There is no denying that some good things happen when we are not eating. Insulin drops dramatically because there are no incoming calories to trigger an insulin response. The liver is emptied of fat in fairly short order. Over time, within three days or so, the body enters a state called “starvation ketosis,” where fat stores are mobilized to fulfill the need for energy—yet at the same time, as I often noticed when I was undergoing regular lengthy fasts, hunger virtually disappears.

Fasting over long periods also turns down mTOR, the pro-growth and pro-aging pathway

Lack of nutrients accelerates autophagy, the cellular “recycling” process that helps our cells become more resilient, and it activates FOXO, the cellular repair genes that may help centenarians live so long.

In practice, that could mean skipping breakfast, eating a first meal at 11 a.m. and finishing dinner by 7 p.m. every evening; or someone could eat breakfast at 8 a.m., another meal at 2 p.m., and nothing thereafter.

The standard 16/8 (sixteen hours of fasting, eight hours to eat) is barely enough for most people, but it can work. Usually a narrower window, such as 18/6 or 20/4, is needed to eke out enough of a caloric deficit.

Most people find this to be the easiest way to reduce their caloric intake, by focusing on when they are eating rather than how much and/or what they are eating.

Shifting the eating window to early in the day, from 8 a.m. to 2 p.m., actually did result in lower twenty-four-hour glucose levels, reduced glucose excursions, and lower insulin levels compared to controls. So perhaps an early-day feeding window could be effective, but in my view sixteen hours without food simply isn’t long enough to activate autophagy or inhibit chronic mTOR elevation, or engage any of the other longer-term benefits of fasting that we would want to obtain.

Another drawback is that you are virtually guaranteed to miss your protein target with this approach

I have become convinced that frequent, prolonged fasting may be neither necessary nor wise for most patients. The cost, in terms of lost lean mass (muscle) and reduced activity levels, simply does not justify whatever benefits it may bring. My rule of thumb for any eating pattern, in fact, is that you must eat enough to maintain lean mass (muscle) and long-term activity patterns.

Protein is actually the most important macronutrient, the one macro that should not be compromised. Remember, most people will be overnourished—but also undermuscled.

(If there is one type of food that I would eliminate from everyone’s diet if I could, it would be fructose-sweetened drinks, including both sodas and fruit juices, which deliver too much fructose, too quickly, to a gut and liver that much prefer to process fructose slowly. Just eat fruit and let nature provide the right amount of fiber and water.)

Many studies have found powerful associations between insufficient sleep (less than seven hours a night, on average) and adverse health outcomes ranging from increased susceptibility to the common cold to dying of a heart attack.

Good sleep, in terms of not only quantity but quality, is critical to our cognitive function, our memory, and even our emotional equilibrium.

Horses can do it standing up; dolphins sleep one half of their brain at a time; and even great white sharks, who never stop moving, spend time in a sleep-like, restful state. Elephants sleep only four hours per day, while the brown bat snoozes for nineteen hours per twenty-four,

We need to sleep about seven and a half to eight and a half hours a night.

Research has found that people who are sleep deprived almost always underestimate its effects on them, because they adapt to it.

This turns out to be one of the most consistent findings in all of sleep research. No fewer than nine different studies have found that sleep deprivation increases insulin resistance by up to a third.

People who sleep eleven hours or more nightly have a nearly 50 percent higher risk of all-cause mortality, likely because long sleep = poor quality sleep, but it may also reflect an underlying illness.

Higher stress levels can make us sleep poorly, as we all know, but poor sleep also makes us more stressed. It’s a feedback loop.

Limiting subjects’ sleep to four or five hours a night suppresses their levels of leptin, the hormone that signals to us that we are fed, while increasing levels of ghrelin, the “hunger” hormone.

Poor sleep has much the same effect, putting the sympathetic nervous system on permanent alert; we get stuck in fight-or-flight mode, and our blood pressure and heart rate remain elevated.

Sleep that is irregular, or fragmented, or not deep enough will not allow the brain to enjoy any of these benefits.

One drug that we do find helpful for assisting with sleep is trazodone,

We typically use it at much lower doses, from one hundred milligrams down to fifty milligrams or even less; the optimal dosing depends on the individual, but the goal is to find the amount that improves their sleep quality without next-day grogginess. (We have also had good results with the supplement ashwagandha.)

Probably the best-validated sleep questionnaire is the Pittsburgh Sleep Quality Index,

There is yet another questionnaire, called STOP-BANG, that correlates pretty strongly with the formal apnea test.[*9] If you snore, have high blood pressure, feel tired most days, or if your partner has observed that you stop breathing occasionally during the night, even for a moment, you are a candidate for further sleep apnea testing by a medical professional.

Most important, you must create an environment for yourself that is conducive to sleeping well. The first requirement for good sleep is darkness.

Their little pinpoint LEDs are more than bright enough to keep you from sleeping well. Digital clocks are especially deadly, not only because of their bright numerals but also because if you wake up and see that it’s 3:31¬†a.m., you might start worrying about your 7 a.m. flight and never fall back asleep.

Therefore, you should also reduce the amount of bright, LED light that you’re exposed to in the evening. A couple of hours before you go to bed, begin turning off unnecessary lights in your house, gradually reducing your light exposure from there. Also, try to swap out blue-intensive LED bulbs for those on the warmer end of the spectrum.

Turn off the computer and put away your phone at least an hour before bedtime. Do NOT bring your laptop or phone into bed with you.

One of the signal events as we are falling asleep is that our body temperature drops by about one degree Celsius. To help that happen, try to keep your bedroom cool—around sixty-five degrees Fahrenheit seems to be optimal. A warm bath before bed may actually help with this process, not only because the bath itself is relaxing but also because when we get out of the bath and climb into our cool bed, our core temperature drops, which signals to our brain that it is time to fall asleep. (There are also a variety of cooling mattresses and mattress toppers out there that could help people who like to sleep cool.)

Alcohol initially acts as a sedative, so it can help us fall asleep more quickly. But as the night wears on, alcohol turns from friend of sleep to foe, as it is metabolized into chemicals that impair our ability to sleep.

Most people think of caffeine as a stimulant that somehow gives us energy, but actually it functions more as a sleep blocker. It works by inhibiting the receptor for a chemical called adenosine, which normally helps us go to sleep every night.

The half-life of caffeine in the body is up to six hours, so if we drink a cup of coffee at noon, we will still have half a cup’s worth of caffeine in our system at 6 p.m. Now multiply this by the number of cups of coffee you drink in a day and work forward from the time of your last cup. If you down one last double espresso at 3 p.m., you will still have a full shot’s worth of caffeine in your system at 9.

Sleep restriction, limiting the hours when they are “allowed” to sleep to six, or less. This basically makes them tired enough that they fall asleep more easily at the end of the day, and (hopefully) their normal sleep cycle is restored.

Taking a nap during the day, while sometimes tempting, can also relieve too much of that sleep pressure, making it harder to fall back asleep at night.

Cultivate sleep pressure is via exercise, particularly sustained endurance exercise (e.g., zone 2), ideally not within two or three hours of bedtime.

A half-hour dose of strong daylight, during the day, helps keep our circadian cycle on track, setting us up for a good night of sleep.

It is also important to mentally prepare ourselves for sleeping. For me, this means avoiding anything that might create stress or anxiety,

A good night of sleep may depend in part on a good day of wakefulness: one that includes exercise, some outdoor time, sensible eating (no late-night snacking), minimal to no alcohol, proper management of stress, and knowing where to set boundaries around work and other life stressors.

Limit yourself to one drink before about 6 p.m.

Don’t eat anything less than three hours before bedtime—and ideally longer.

Abstain from stimulating electronics, beginning two hours before bed.

Avoid doing anything that is anxiety-producing or stimulating,

Spend time in a sauna or hot tub prior to bed.

The room should be cool, ideally in the midsixties.

Darken the room completely.

Use an eye shade. I use a silky one called Alaska Bear that costs about $8

Fix your wake-up time—and don’t deviate from it, even on weekends.

If you find yourself lying awake in bed, unable to get back to sleep, my advice is to stop fighting it. Get up, go into another room and do something relaxing. Fix a cup of tea (noncaffeinated, obviously), and read a (preferably boring) book until you feel sleepy again.

The most effective treatment is a form of psychotherapy called Cognitive Behavioral Therapy for Insomnia, or CBT-I.

Another very direct way in which mental health affects lifespan is via suicide, which ranks among the top ten causes of death across all age groups,

Not all suicides jump from bridges. Many more people sort of slow-roll into misery and early death via various roundabout routes, letting stress and anger erode their health, or falling into self-medicating addictions to alcohol and drugs, or engaging in other reckless, life-endangering behaviors that mental health professionals call parasuicide.

The CDC estimates that more than one hundred thousand Americans died from drug overdoses between April 2020 and April 2021, about as many as died from diabetes.

These “accidental” overdoses account for almost 40 percent of all accidental deaths, a category that also includes automobile accidents and deaths from falls.

I’ve come to believe that emotional health may represent the most important component of healthspan. Nothing else about longevity is really worth much without some degree of happiness, fulfillment, and connection to others.

There are many rules at the Bridge, and one of the most important ones is no minimizing. You are not allowed to minimize anything that someone else is saying, and you are especially not allowed to minimize your own experiences.

The Trauma Tree. The idea behind it is that certain undesirable behaviors that we manifest as adults, such as addiction and uncontrolled anger, are actually adaptations to the various types of trauma we suffered in childhood. So while we only see the manifestation of the tree above the ground, the trunk and branches, we need to look underground, at the roots, to understand the tree completely. But the roots are often very well hidden,

Trauma generally falls into five categories: (1) abuse (physical or sexual, but also emotional or spiritual); (2) neglect; (3) abandonment; (4) enmeshment (the blurring of boundaries between adults and children); and (5) witnessing tragic events.

There can be “big-T” trauma or “little-t” traumas.

Both types can do tremendous damage, but little-t trauma is more challenging to address—in part, I suspect, because we are more inclined to dismiss it.

Trauma, big T or little t, means having experienced moments of perceived helplessness. The situations in question may or may not have been life-or-death, he explained, “but to a child with an undeveloped brain, it may have seemed that way.”

There is no bright line between trauma and adversity; terrible as it was, my own experience had made me stronger in some ways. Julie’s question is a pretty good litmus test: Would I want my child to experience it?

This dysfunction is represented by the four branches of the trauma tree: (1) addiction, not only to vices such as drugs, alcohol, and gambling, but also to socially acceptable things such as work, exercise, and perfectionism (check); (2) codependency, or excessive psychological reliance on another person; (3) habituated survival strategies, such as a propensity to anger and rage (check); (4) attachment disorders, difficulty forming and maintaining connections or meaningful relationships with others

Emotional health has more to do with the way we regulate our emotions and manage our interpersonal relationships.

Male rage is helplessness masquerading as frustration.”

I learned that children don’t respond to a parent’s anger in a logical way. If they see me screaming at a driver who just cut me off, they internalize that rage as though it were directed to them. Second, trauma is generational, although not necessarily linear. Children of alcoholics are not inevitably destined to become alcoholics themselves, but one way or another, trauma finds its way down the line.

As Terry had written: “Family pathology rolls from generation to generation like a fire in the woods taking down everything in its path until one person, in one generation, has the courage to turn and face the flames. That person brings peace to his ancestors and spares the children that follow.”

One helpful model that Terry had taught me was to think about my relationships as akin to a delicate ecosystem, a kind of emotional ecology. Why would I want to poison the environment in which I had to live?

I made sure to spend time with my kids—one on one, no phones—every day that I was home. I would check in with Jill on her experience (not “events”) each day. I limited my phone time and my work hours to a strict window. One day a week, typically Saturday or Sunday, I would refrain from doing any work at all, something that went against decades of ingrained habit. Even more amazing, Jill and I went on an actual vacation for the first time in years, just the two of us, no kids.

Reframing entails taking a step back from a situation and then asking yourself, What does this situation look like through the other person’s eyes? How do they see it? And why is your time, your convenience, or your agenda any more important than theirs?

I had picked up David Brooks’s book The Road to Character. On the plane, I read the part where Brooks makes a key distinction between “resume virtues,” meaning the accomplishments that we list on our CV, our degrees and fellowships and jobs, versus “eulogy virtues,” the things that our friends and family will say about us when we are gone.

I focused on eulogy virtues, not resume virtues. I worked on being more relational, more present with my family. I tried to practice reframing. But something still felt off. Even as I worked on my relationships with those closest to me, I still had a major blind spot: my relationship with myself.

I was assigned to write out a list of forty-seven affirmations, representing one positive statement about myself for each year of my life.

I hadn’t been protected. I hadn’t felt safe. My trust had been broken by people who were close to me. I felt abandoned. All of that had manifested itself as my own self-loathing as an adult; I had become my own worst enemy.

It reminded me of this observation by Jacob Riis, the great Danish American journalist and social reformer: “When nothing seems to help, I go back and look at a stonecutter hammering away at his rock perhaps a hundred times without as much as a crack showing in it. Yet at the hundred-and-first blow it will split in two, and I know it was not the last blow that did it, but all that had gone before.”

All of these modalities are powerful and potentially useful, but we need to think of them as merely adjuncts to the deep and often very unpleasant, uncomfortable, at times very slow—at other times too fast—self-exploration that is required in real psychotherapy.

Learn to understand the warning signs and the systems failures that could lead to a blow-up in my own life, to prevent it from ever happening again.

The tools that I use, derive from a school of psychology known as dialectical behavior therapy, or DBT, developed in the 1990s by Marsha Linehan.

One thing I like about DBT is that it is backed up by evidence: clinical trials have found it to be effective in helping suicidal and self-harming patients stop their dangerous behavior.

Practicing DBT means literally working through a workbook with a DBT therapist, doing exercises every day.

Aim to break the chain reaction of negative stimulus → negative emotion → negative thought → negative action.

The overarching theme is mindfulness, which gives you the ability to work through the other four: emotional regulation (getting control over our emotions), distress tolerance (our ability to handle emotional stressors), interpersonal effectiveness (how well we make our needs and feelings known to others), and self-management (taking care of ourselves, beginning with basic tasks

One of the most powerful exercises I learned was to simply listen to my self-talk. I would record voice memos to myself on my phone, after I did anything that could produce self-judgment, such as archery or driving my race-car simulator, or even just cooking dinner, and send each one to my therapist.

My therapist at PCS told me to imagine instead that my best friend had performed exactly as I had done. How would I speak to him? Would I berate him the way I often berated myself?

As Terry Real had pointed out long ago, this anger was rooted in shame, but very often my anger would also create more shame. If I yell at my kids, for example, especially when I do it because I’m upset about something else, I feel shame. That shame then becomes an obstacle to my ability to reconcile with them, so I feel more shame. It’s like I’m digging myself into a hole,

One simple tactic that I use to cope with mounting emotional distress is inducing an abrupt sensory change—typically, by throwing ice water on my face or, if I’m really struggling, taking a cold shower or stepping into an ice bath. This simple intervention stimulates an important cranial nerve, the vagus nerve, which causes our heart rate and respiratory rate to slow and switches us into a calm, parasympathetic mode (and out of our fight-or-flight sympathetic mode).

Another technique I have grown very fond of is slow, deep breathing: four seconds to inhale, six seconds to exhale. Repeat. As the breath goes, the nervous system follows.

One tactic that I’ve found especially helpful is called opposite action—that is, if I feel like doing one thing (generally, not a helpful or positive thing), I’ll force myself instead to do the exact opposite. By doing so, I also change the underlying emotions.

Changing the behavior can change the mood. You do not need to wait for your mood to improve to make a behavior change.

When I’m alone, rucking serves as a mindfulness practice, a kind of walking meditation. No phone, no music, no podcasts. Just the sounds of nature, and of my heavy breathing. This is another example of how action can lead us into a better mental state. And as Michael Easter pointed out to me, there is actual research suggesting that exposing oneself to the fractal geometric patterns in nature can reduce physiological stress, and that these effects show up on an EEG.

Each session begins with a physical check-in: How am I feeling? How have I slept (a big one)? Am I in physical pain? Am I in conflict? Then we dissect and discuss the events and issues of the week in minute detail. No topic is too insignificant.

You have to believe you can change—and that you deserve better.

It’s difficult for many people, myself included at one point, to recognize that they have a problem, admit that they need help, and then take action, particularly if it means talking about it openly with others, or taking time off work, or dealing with the expense of treatment.

I began to notice something I had never experienced before: I found more joy in being than in doing. For the first time in my life, I felt that I could be a good father. I could be a good husband. I could be a good person.

There’s a quote from Paulo Coelho that I think about often: “Maybe the journey isn’t so much about becoming anything,” he writes. “Maybe it’s about unbecoming everything that isn’t really you, so you can be who you were meant to be in the first place.”

The most important ingredient in the whole longevity equation is the why. Why do we want to live longer? For what? For whom?

“If you want to find someone’s true age, listen to them. If they talk about the past and they talk about all the things that happened that they did, they’ve gotten old. If they think about their dreams, their aspirations, what they’re still looking forward to—they’re young.”

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