My rating: 3 of 5 stars (Goodreads)

It’s a very long book with some helpful background science and medical information. But I can’t say that I really learned anything new. It may or less reinforces things that I have read or heard previously. For someone younger than 40, it may be a cautionary tale and a more valuable read than for someone as old as me.

My notes from the book.

The odds are overwhelming that you will die as a result of one of the chronic diseases of aging that I call the Four Horsemen: heart disease, cancer, neurodegenerative disease, or type 2 diabetes and related metabolic dysfunction.

Exercise is by far the most potent longevity “drug.” No other intervention does nearly as much to prolong our lifespan and preserve our cognitive and physical function. But most people don’t do nearly enough—and exercising the wrong way can do as much harm as good.

Our tactics in Medicine 3.0 fall into five broad domains: exercise, nutrition, sleep, emotional health, and exogenous molecules.

So we will break down this thing called exercise into its most important components: strength, stability, aerobic efficiency, and peak aerobic capacity. Increasing your limits in each of these areas is necessary if you are hoping to reach your limit of lifespan and healthspan.

My point is that if you really stop to consider the kind of aerobic fitness that most people actually need in the course of their lives, it basically boils down to being really good at going slow for a long time, but also able to go hard and fast when needed.

The best science out there says that what you eat matters, but the first-order term is how much you eat: how many calories you take into your body.

You may have heard of this gene, which is called APOE, because of its known effect on Alzheimer’s disease risk.¨

The authors of the study, published in Nature, speculated that rapamycin might extend lifespan “by postponing death from cancer, by retarding mechanisms of aging, or both.”¨

This is not an atypical scenario: 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. It is the most prevalent hereditary risk factor for heart disease, and its danger is amplified by the fact that it is still largely flying under the radar of Medicine 2.0, although that is beginning to change.

¨This is why, if you have a history of premature heart attacks in your family, you should definitely ask for an Lp(a) test. We test every single patient for Lp(a) during their first blood draw.¨

The single most powerful item in our preventive tool kit is exercise, which has a two-pronged impact on Alzheimer’s disease risk: it helps maintain glucose homeostasis, and it improves the health of our vasculature.¨

Strength training is likely just as important. 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.¨

Sleep disruptions and poor sleep are potential drivers of increased risk of dementia. If poor sleep is accompanied by high stress and elevated cortisol levels, as in Stephanie’s case, that acts almost as a multiplier of risk, as it contributes to insulin resistance and damaging the hippocampus at the same time.¨

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.¨

In Medicine 3.0, we have five tactical domains that we can address in order to alter someone’s health. The first is exercise, which I consider to be by far the most potent domain in terms of its impact on both lifespan and healthspan.¨

Next is diet or nutrition—or as I prefer to call it, nutritional biochemistry. The third domain is sleep, which has gone underappreciated by Medicine 2.0 until relatively recently. The fourth domain encompasses a set of tools and techniques to manage and improve emotional health. Our fifth and final domain consists of the various drugs, supplements, and hormones that doctors learn about in medical school and beyond. I lump these into one bucket called exogenous molecules, meaning molecules we ingest that come from outside the body.¨

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.¨

The three dimensions in which we want to optimize our fitness are aerobic endurance and efficiency (aka cardio), strength, and stability. All three of these are key to maintaining your health and strength as you age.¨

In San Millán’s view, healthy mitochondria are key to both athletic performance and metabolic health. 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. Mitochondrial health becomes especially important as we grow older, because one of the most significant hallmarks of aging is a decline in the number and quality of our mitochondria.¨

Strength training, especially with heavy weights, stimulates the growth of bone—more than impact sports such as running…



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