Lifespan: Why We Age—and Why We Don't Have To

by David A. Sinclair

The big shock was that the health benefits were remarkably similar no matter how much running the people had done. Even about ten minutes of moderate exercise a day added years to their lives.35 There is a difference between a leisurely walk and a brisk run, however. To engage our longevity genes fully, intensity does matter. Mayo Clinic researchers studying the effects of different types of exercise on different age groups found that although many forms of exercise have positive health effects, it’s high-intensity interval training (HIIT)—the sort that significantly raises your heart and respiration rates—that engages the greatest number of health-promoting genes, and more of them in older exercisers.36

In other words: exercise turns on the genes to make us young again at a cellular level.

Often I’m asked, “Can I just eat what I want and run off the extra calories?” My answer is “Unlikely.”

Because as it turns out, exposing your body to less-than-comfortable temperatures is another very effective way to turn on your longevity genes. When the world takes us out of the thermoneutral zone—the small range of temperatures that don’t require our bodies to do any extra work to stay warm or cool off—all sorts of things happen.

Targeting Aging with Metformin (TAME)

The benefit of working with yeast, though, is that the worst-case scenario in any experiment is a yeast massacre.

Charles Brenner, who is now the head of biochemistry at the University of Iowa, discovered in 2004 that a form of vitamin B3 called nicotinamide riboside, or NR, is a vital precursor of NAD. He later found that NR, which is found in trace levels in milk, can extend the lifespan of yeast cells by boosting NAD and increasing the activity of Sir2. Once a rare chemical, NR is now sold by the ton each month as a nutraceutical. Meanwhile, on a parallel path, researchers, including us, were homing in on a chemical called nicotinamide mononucleotide, or NMN, a compound made by our cells and found in foods such as avocado, broccoli, and cabbage. In the body, NR is converted into NMN, which is then converted into NAD.

DELETING THE ZOMBIE SENESCENT CELLS IN OLD TISSUES. Thanks to the primordial survival circuit we’ve inherited from our ancestors, our cells eventually lose their identities and cease to divide, in some cases sitting in our tissues for decades. Zombie cells secrete factors that accelerate cancer, inflammation, and help turn other cells into zombies. Senescent cells are hard to reverse aging in, so the best thing to do is to kill them off. Drugs called senolytics are in development to do just that, and they could rapidly rejuvenate us.

Today, I can read an entire human genome of 25,000 genes in a few days for less than a hundred dollars on a candy bar–sized DNA sequencer called a MinION that I plug into my laptop. And that’s for a fairly complete readout of a human genome, plus the DNA methyl marks that tell you your biological age.

In 1968, as the global population approached 3.5 billion, Stanford University professor Paul Ehrlich and his wife, associate director of Stanford’s Center for Conservation Biology Anne Ehrlich, sounded the Malthusian alarm once again in a best-selling book called The Population Bomb.

Bill Gates made a convincing argument for why improving human health is money well spent, and won’t lead to overpopulation, in his 2018 video “Does Saving More Lives Lead to Overpopulation?”56 The short answer is: No.

• I take 1 gram (1,000 mg) of NMN every morning, along with 1 gram of resveratrol (shaken into my homemade yogurt) and 1 gram of metformin.7 • I take a daily dose of vitamin D, vitamin K2, and 83 mg of aspirin. • I strive to keep my sugar, bread, and pasta intake as low as possible. I gave up desserts at age 40, though I do steal tastes. • I try to skip one meal a day or at least make it really small. My busy schedule almost always means that I miss lunch most days of the week. • Every few months, a phlebotomist comes to my home to draw my blood, which I have analyzed for dozens of biomarkers. When my levels of various markers are not optimal, I moderate them with food or exercise. • I try to take a lot of steps each day and walk upstairs, and I go to the gym most weekends with my son, Ben; we lift weights, jog a bit, and hang out in the sauna before dunking in an ice-cold pool. • I eat a lot of plants and try to avoid eating other mammals, even though they do taste good. If I work out, I will eat meat. • I don’t smoke. I try to avoid microwaved plastic, excessive UV exposure, X-rays, and CT scans. • I try to stay on the cool side during the day and when I sleep at night. • I aim to keep my body weight or BMI in the optimal range for healthspan, which for me is 23 to 25.

so if I do take a supplement, I look for a large manufacturer with a good reputation, seek highly pure molecules (more than 98 percent is a good guide), and look for “GMP” on the label, which means the product was made under “good manufacturing practices.”