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

by David A. Sinclair

Everyone in my family, from my grandmother to my youngest son, has had their genes analyzed by one of the companies that offer these services.

We know that aging makes you more likely to die, too, but we’ve accepted it as part of life.

starker

corer

nigh.

There is nothing more dangerous to us than age. Yet we have conceded its power over us. And we have turned our fight for better health in other directions.

geriatricians,

dismal

It doesn’t take studies and statistics to know what’s happening, though. It’s all around us, and the older we get, the more obvious it becomes. We get to 50 and begin to notice we look like our parents, with graying hair and an increasing number of wrinkles. We get to 65, and if we haven’t faced some form of disease or disability yet, we consider ourselves fortunate. If we’re still around at 80, we are almost guaranteed to be combating an ailment that has made life harder, less comfortable, and less joyful. One study found that 85-year-old men are diagnosed with an average of four different diseases, with women of that age suffering from five. Heart disease and cancer. Arthritis and Alzheimer’s. Kidney disease and diabetes. Most patients have several additional undiagnosed diseases, including hypertension, ischemic heart disease, atrial fibrillation, and dementia.18 Yes, these are different ailments with different pathologies, studied in different buildings at the National Institutes of Health and in different departments within universities.

But aging is a risk factor for all of them. In fact, it’s the risk factor. Truly, by comparison, little else matters.

geroncogenesis.

But consider this: though smoking increases the risk of getting cancer fivefold, being 50 years old increases your cancer risk a hundredfold. By the age of 70, it is a thousandfold.

In a world in which we seem to agree on very little, the feeling that “it’s just the way it goes” is almost universal.

The manual therefore calls aging an “inevitable, irreversible decline in organ function that occurs over time even in the absence of injury, illness, environmental risks, or poor lifestyle choices.”

I believe that aging is a disease. I believe it is treatable. I believe we can treat it within our lifetimes. And in doing so, I believe, everything we know about human health will be fundamentally changed.

stupor.

proteostasis,

thwarting

ebbs

And overwhelmingly that advice comes down to eating more vegetables, legumes, and whole grains, while consuming less meat, dairy products, and sugar.

After twenty-five years of researching aging and having read thousands of scientific papers, if there is one piece of advice I can offer, one surefire way to stay healthy longer, one thing you can do to maximize your lifespan right now, it’s this: eat less often.

intentional asceticism.”

transient.

shun:

wry

When we investigate places like this, and as we seek to apply research about fasting to our modern lives, we find that there are scores of ways to calorie restrict that are sustainable, and many take the form of what has come to be known as periodic fasting—not being hungry all the time but using hunger some of the time to engage our survival circuit. Over time, some of these ways of limiting food will prove to be more effective than others. A popular method is to skip breakfast and have a late lunch (the 16:8 diet). Another is to eat 75 percent fewer calories for two days a week (the 5:2 diet). If you’re a bit more adventurous, you can try skipping food a couple of days a week (Eat Stop Eat), or as the health pundit Peter Attia does, go hungry for an entire week every quarter. The permutations of these various models for extending life and health are being worked out in animals and will be worked out in people, too. The short-term studies are promising. I suspect the long-term research will be, too. In the meantime, however, almost any periodic fasting diet that does not result in malnutrition is likely to put your longevity genes to work in ways that will result in a longer, healthier life.

satiates

If you want to keep mTOR from being activated too much or too often, limiting your intake of amino acids is a good way to start, so inhibiting this particular longevity gene is really as simple as limiting your intake of meat and dairy.

methionine.

telomeres

Centers for Disease Control and Prevention and published in 2017, individuals who exercise more—the equivalent of at least a half hour of jogging five days a week—have telomeres that appear to be nearly a decade younger than those who live a more sedentary life.31 But why would exercising delay the erosion of telomeres?

There’s really no way around this. We all need to be pushing ourselves, especially as we get older, yet only 10 percent of people over the age of 65 do.32 The good news is that we don’t have to exercise for hours on end. One recent study found that those who ran four to five miles a week—for most people, that’s an amount of exercise that can be done in less than 15 minutes per day—reduce their chance of death from a heart attack by 40 percent and all-cause mortality by 45 percent.33 That’s a massive effect.

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.

leisurely

hypoxic

Being hungry is necessary for CR to work because hunger helps turn on genes in the brain that release longevity hormones, at least according to a recent study by Dongsheng Cai at the Albert Einstein College of Medicine.

Would a combination of fasting and exercise lengthen your lifespan? Absolutely. If you manage to do both these things: congratulations, you are well on your way. But there is plenty more you can do.

Because as it turns out, exposing your body to less-than-comfortable temperatures is another very effective way to turn on your longevity genes.

Then, in 2017, the connection between the UCP2 gene and aging came full circle, thanks to researchers from Université Laval in Quebec: not only could UCP2 make mice “run cold,” the Canadian team demonstrated, but colder temperatures could change the way the gene operated, too—through its ability to rev up brown adipose tissue.

That is why we need to learn more about how to chemically substitute for brown adipose tissue thermogenesis.

dinitrophenol

Another thing you can try is activating the mitochondria in your brown fat by being a bit cold. The best way to do this might be the simplest—a brisk walk in a T-shirt on a winter day in a city such as Boston will do the trick. Exercising in the cold, in particular, appears to turbocharge the creation of brown adipose tissue.52 Leaving a window open overnight or not using a heavy blanket while you sleep could help, too.

invigorated

snicklefritz,

although the researchers were correct to point out that part of the effect could be due to the fact that those who are sick or disabled don’t go to the sauna.

pampered

But dealing with biological adversity is one thing. Overwhelming genetic damage is another.

There’s a reason why smokers seem to age faster: they do age faster.

flummoxed

catalase,