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

by David A. Sinclair

Horvath Clock—an accurate way of estimating someone’s biological age by measuring thousands of epigenetic marks on the DNA,

called methylation. We tend to think of aging as something that begins happening to us at midlife, because that’s when we start to see significant changes to our bodies. But Horvath’s clock begins ticking the moment we are born.

The age we have vs the age we feel.

were being caused not by mutation but by the epigenetic changes that come as a result of DNA damage signals.

that aging is not an inevitable part of life but rather a “disease process with a broad spectrum of pathological consequences.”4 In this way of thinking, cancer, heart disease, Alzheimer’s, and other conditions we commonly associate with getting old are not necessarily diseases themselves but symptoms of something greater. Or, put more simply and perhaps even more seditiously: aging itself is a disease.

Separating aging from disease obfuscates a truth about how we reach the ends of our lives: though it’s certainly important to know why someone fell from a cliff, it’s equally important to know what brought that person to the precipice in the first place.

It’s possible that interventions aimed at slowing telomere deterioration will improve people’s long-term well-being. Maintaining proteostasis, preventing deregulation of nutrient sensing, thwarting mitochondrial dysfunction, stopping senescence, rejuvenating stem cells, and decreasing inflammation might all be ways to delay the inevitable.

There will always be good and bad choices. And that starts with what we put into our bodies. And what we don’t.

other animal studies tell us is that it’s hard to “age out” of the longevity benefits of calorie restriction, but it’s probably better to start earlier than later, perhaps after age 40, when things really start to go downhill, molecularly speaking.

Oh oh...

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.

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.

There’s a lot of methionine in beef, lamb, poultry, pork, and eggs, whereas plant proteins, in general, tend to contain low levels of that amino acid—enough to keep the light on, as it were, but not enough to let biological complacency set in.

We can’t live without them, but most of us can definitely stand to get less of them, and we can do that by lowering our consumption of foods that many people consider to be the “good animal proteins,” chicken, fish, and eggs—particularly when those foods aren’t being used to recover from physical stress or injury.

study funded by the 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.

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.

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 You’ll know you are doing vigorous activity when it feels challenging. Your breathing should be deep and rapid at 70 to 85 percent of your maximum heart

exercise-induced stress can bring them back to the levels associated with youth. In other words: exercise turns on the genes to make us young again at a cellular level.

Being hungry is necessary for CR to work because hunger helps turn on genes in the brain that release longevity hormones,

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.

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.

Those who used a sauna with great frequency—up to seven times a week—enjoyed a twofold drop in heart disease, fatal hearts attacks, and all-cause mortality events over those who heat bathed once per week.

one thing is clear: it does us little good to spend our entire lives in the thermoneutral zone. Our genes didn’t evolve for a life of pampered comfort. A little stress to induce hormesis once in a while likely goes a long way.

An admittedly small study of healthy volunteers claimed that the DNA methylation age of blood cells is reversed within a week and, astoundingly, only ten hours after taking a single 850 mg pill of metformin.

Why short telomeres cause senescence has been mostly worked out. A very short telomere will lose its histone packaging, and, like a shoelace that’s lost an aglet, the DNA at the end of the chromosome becomes exposed.

The cell detects the DNA end and thinks it’s a DNA break. It goes to work to try to repair the DNA end, sometimes fusing two ends of different chromosomes together, which leads to hypergenome instability as chromosomes are shredded during cell division and fused again, over and over, potentially becoming a cancer.

we’re moving into a world in which treatment decisions no longer have to be based on what is best for most people most of the time.

Helping more people reach that potential is a matter of bringing costs down and using emerging treatments, therapies, and technologies in a way that truly puts individuals at the center of their own care. And that’s not just about diagnosing people right when something does go wrong—it’s also about knowing what to do for us, as individuals, even before a diagnosis has been made.

we are about to enter a world in which our genomes will be sequenced, stored, and already red-lighted for treatments that have been demonstrated to have adverse effects on people with similar gene types and combinations as we have.

we’ll be green-lighted for treatments that are known to work for people with similar genes, even if those treatments don’t work for most other people most of the time.

“Embrace things rather than try and fight them. Work with things rather than try and run from them or prohibit them.”3 We often fail to acknowledge that knowledge is multiplicative and technologies are synergistic.

and to better understand the changes that must take place if we are to meet a world of significantly prolonged human healthspans and lifespans with equity, equality, and human decency.

The question, then, is not whether the natural and unnatural bounties of our Earth can sustain 8 billion, 16 billion, or 20 billion people. That’s a moot point. The question is whether humans can continue to develop the technologies that will permit us to stay ahead of the curve in the face of population growth, and indeed make the planet a better place for all creatures.

When those years do come, how do we wish to spend them? Will we follow the perilous path that ultimately leads to a dystopian doom? Will we band together to create a world that exceeds our wildest utopian dreams?

Preventing disease and disability is possibly the single most impactful thing we can do to avert a global crisis precipitated by climate change, crippling economic burdens, and future social upheavals.

define aging as a disease.

Researchers working on aging will compete on equal footing with researchers working to cure every other disease in the world.

most Australians and Britons rarely assume that their way of doing things is the best. Americans, however, often believe that their way of doing things is assuredly the best.

It does not matter if we can extend lifespans if we cannot extend healthspans to an equal extent.

the fight against aging isn’t about ending death; it’s about prolonging healthy life and giving more people the chance to meet death on far better terms—indeed,

Longer, healthier lives will do us little good if we consume ourselves into oblivion. The imperative is clear: whether or not we increase human longevity, our survival depends on consuming less, innovating more, and bringing balance to our relationship with the bounty of our natural world.

if I don’t do anything at all—and it’s not pretty. So what do I have to lose? And so, with all that on the table, what do I do? • 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. About fifty times a day I’m asked about supplements. Before I answer, let me ...

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