Outlive

This means keeping watch for the earliest signs of trouble. In my patients, 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. Lipoproteins, which we will discuss in detail in the next chapter, are also important, especially triglycerides; 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 of which may show up many years before a patient would meet the textbook definition of metabolic syndrome.

This means keeping watch for the earliest signs of trouble. In my patients, 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.

On a more macro level, consuming large quantities of liquid fructose simply overwhelms the ability of the gut to handle it; the excess is shunted to the liver, where many of those calories are likely to end up as fat.

The mechanisms are a bit complicated, but the bottom line is that even though it is rich in energy, 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.

Fructose isn’t the only thing that creates uric acid; foods high in chemicals called purines, such as certain meats, cheeses, anchovies, and beer, also generate uric acid.

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)

If you meet three or more of these criteria, then you have the metabolic syndrome—along with as many as 120 million other Americans, according to a 2020 article in JAMA.

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.

For the moment, though, let’s think about the fact that all of what we’ve talked about in this chapter, from mTOR and rapamycin to caloric restriction, points in one direction: that what we eat and how we metabolize it appear to play an outsize role in longevity.

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.

data are unambiguous: exercise not only delays actual death but also prevents both cognitive and physical decline, better than any other intervention. We also tend to feel better when we exercise, so it probably has some harder-to-measure effect on emotional health as well.