Q&A: How Harvard's David Sinclair is Fighting Aging—and How You Can, Too

What if someone told you that you could live for another 100 years... while remaining physically healthy and mentally sharp? You’d probably brush it off as science fiction. Turns out, it may be closer to fact. At least, if David Sinclair, PhD has anything to say about it. He’s the author of the New York Times bestseller, Lifespan: Why We Age and Why We Don’t Have To, a thrilling new book that asserts that, contrary to scientific dogma, aging is not inevitable—and makes the case for why this shouldn't be such a radical idea.  

As a world-renowned expert on the subject, David Sinclair is qualified to make such bold statements about aging. He’s a professor of genetics at Harvard Medical School, a co-director of the Paul F. Glenn Center for the Biology of Aging, and is Chairman of our Scientific Advisory Board at InsideTracker. He’s a popular guy outside of science, too. David recently joined Joe Rogan to teach him about aging, starred in a riveting NPR video feature on longevity, stopped by Good Morning America, and has appeared on Dr. Peter Attia's podcast and Dave Asprey's Bulletproof podcast to explain how to live better for longer.

David makes a convincing argument for why it’s critical that we as a society reframe how we think about aging: there are ethical, social, economic, and ecological implications tied to our collective longevity. It’s one reason why here at InsideTracker, we developed the InnerAge test—we’ve long been advocates of the idea that you can improve your lifespan with simple changes. 



A painful descent into old age isn't something you have to accept. David Sinclair explains why in this Q&A. 

In your book, you state there is “no biological law that says we must age. That’s exciting news for most of us. What do you mean by that?

David: “Well, we're biological, and so we take in energy as food, and we can use that energy to repair our bodies and preserve information [at the cellular level]. There's no law of physics that says we can’t live a lot longer. We know that some mammals live over 200 years, and some humans live between 100 and 120. And so we've got at least 40 years—and possibly 120—to play with here.”

People tend to think of aging as something that’s chronological and inevitable. How do you define it?

“As a scientific definition, I'm proposing that aging is a loss of information—the information that keeps our cells healthy, the information that tells the cells which genes to read throughout our lives. And aging is a manifestation of cells losing their ability to read the right genes at the right time, which leads to cells losing their identity and tissues failing.”

That isn’t how aging is defined from a regulatory perspective though, right?

“The regulatory definition, currently, is that aging is something different than a disease. The reason is that even though it satisfies the criteria of a disease—which is a decline in function over time leading to death—aging is separated because it happens to more than 50% of us. And I'd argue that just because aging happens to more than half of us, is no reason to not include it as a disease. In fact, I would say it's even more important that we work on trying to combat it, because aging is the main cause of all major diseases in society now.”

Many people worry that extending the global population’s lifespan will throw Earth out of whack. But you argue we should fight aging as a disease, helping more people live longer?

“Well, we're already out of whack and we need a solution. I crunched the numbers and took a picture of what happens if we're not successful at helping people live healthier and longer, versus if we do. And you get a very different answer when you do that. The answer that I came up with, was that a world where people can be healthy beyond 80, is a much richer world. That's a world with money to fight climate change—tens of trillions of dollars—for the next 50 years, money that can be spent on education, on building sea walls, on paying social security. And to me, that is the solution to our problems, it's not the cause of them.” 

So we aren’t in danger of “overpopulating” the planet by improving lifespan...

“The human population is leveling off. The amount of old people who stick around is not going to be anywhere near as many as people imagine. In many countries, they're already declining in population and the number of older people is just going up as a percentage, ready to bankrupt those countries. What you really want is a lot of healthy older people who are wise and productive, versus a population of people who you have to spoon feed and send to doctors. Anyone who argues that we shouldn't be fighting against nursing homes—I think they should go spend a day in a nursing home.”

You reveal an exciting new theory in your book, called the Information Theory of Aging. Can you explain this to our readers in simple terms?

“The new idea is that we have two major types of information stored in the body: One is digital, one is analog. The digital information is our genome, which surprisingly lasts way longer than 80 years (that's a new discovery), but it's the analog information that I find is the problem. The analog information is the epigenome—the structures within the cell that allow some genes to be read while keeping others silent. Because the analog information is very hard to preserve, that’s the first one to fail. And that's what I believe causes aging.”

Can people address this “loss of information” with simple interventions like diet and lifestyle modifications?

“The most important thing is to eat less often. That's not malnutrition; it's not starvation. I don't want any teenagers to use this as a reason to not eat enough—but most adults eat too much and they eat too often. And based on some recent results in mice, and also in humans, it looks like it's just as important when you eat, as what you eat—and perhaps even more important. I'm suggesting that three square meals a day is not optimal for longevity. There are various varieties of fasting that you can do, which I think are potentially helpful. We don't know which one's best, but I don’t eat breakfast, except for maybe a few bites of yogurt, and then I don't eat until late afternoon, sometimes all the way to dinner.” 

How exactly does fasting promote longevity?

“We found that longevity genes are turned on by fasting. They're also turned on particularly by high intensity exercise. Being out of breath for 10 minutes every day or every other day is linked to a reduction in different diseases—certainly heart disease. My understanding is that we used to think you had to be a marathon runner to get the full benefits of exercise, but short, high intensity interval training seems to be almost as good. And the worst thing you can do [for aging] is to never get out of breath.”

In your book, you list 9 hallmarks of aging. You say addressing just one hallmark can slow down aging. Can you explain a few of these and tell us how to address them?

1. Genomic instability

"DNA damage accelerates epigenetic aging and the loss of information at the epigenetic level and the genetic level [causing genomic instability]. We know that breaking a chromosome is the best way to accelerate aging. We've done this in mice and it's not pretty. Even just a few DNA breaks can accelerate aging. To avoid breaking DNA, try to avoid using microwaves, don’t have too many x-rays done unnecessarily, or CT scans; I think CT scans are essential, but don't have CT scans done every year just because you're curious what's going on inside. That’s my view. Avoid radiation of the type that will break DNA.”

2. Deregulated nutrient sensing

"This includes insulin insensitivity, Type 2 Diabetes—which is very bad for aging, probably the worst one we know of.  The way to combat that is: don’t be overweight, keep exercising and lift weights."

3. Mitochondrial dysfunction:

"Mitochondria are like the battery packs in the cell; these are important for burning fat. The key points here are: the more you exercise, the more mitrochondria you will have and calorie restriction boosts mitochondrial activity."



4. Loss of proteostasis:

“This is a loss of protein homeostasis due to misfolded proteins—old proteins [at the cellular level]. What people can do for that is to fast. Fasting a little bit is good, fasting for three days is even better at reversing misfolded proteins and inducing chaperone-mediated autophagy [cellular regeneration], which helps maintain cellular proteostasis.”

5. Telomere shortening

 "This will happen naturally as cells divide, but will also be accelerated by free radicals and DNA damage. I’m not a big fan of antioxidants as they haven’t done a lot in studies. But you can try to bolster the body’s natural defenses against DNA damage, which are the hormesis effects [like fasting and high intensity exercise]. Also, you could use supplements like resveratrol or an NAD-booster to try to get sirtuins more active, and that seems to slow down telomere shortening; it was shown by Dr. Lenny Guarente."

Should people start as early as possible with these anti-aging interventions, or is there an optimal age at which to begin?

“Well, because we don’t yet have an epigenetic 'reset button' for humans, we have to be working diligently at [aging interventions] to give us a chance at improving. I started when I was 30 years old, and I don’t regret it at all. Even in my 20s I was pretty good at my diet. We’ve seen in animals that if you intervene early and calorie-restrict or give them a molecule like rapamycin earlier on, it works better.

Is there a point of no return, at which it’s impossible to turn back the aging clock?

“Well yeah, a very old, morbid mouse will never live longer, but you can start treating them pretty late with rapamycin––I think it's 19-20 months of age, which would be a 60-year-old human. You know, I met Norman Leary at 97, and the guy is doing great… but it's a spectrum. It gets harder the older you get, so it’s better to prevent aging than to try to reverse it.”

You’ve noted some significant improvements in your dad, who began making changes very late in his life but now, at 80 years of age, has the vigor and mental stamina of a 30-year-old.

“Yes, but it's also worth noting that most of the time [when he was making these changes] he didn't see an immediate difference. So those people who decide, ‘Oh, I'm not feeling any different, but I took my resveratrol today’—that's naive, to think that you'll suddenly be young. It's an investment in the future.”

True. And you also need to look inside the body to observe change, right? Which is what we do here at InsideTracker. 

“Well, that's important too. I told somebody yesterday, InsideTracker looks at liver enzymes. If your liver enzymes are out of whack, unless you're dying, you're not going to know if they improve. But they did improve when my father and I both took NMN. You can't just base it on how you feel. That's a really important point.”

What about gender differences in aging—should we take gender into account when considering interventions?

“What we're discovering in many of the studies is that gender really makes a difference, particularly when it comes to longevity. There are treatments that work in female mice but not in males, and vice versa. And so, what this tells me is that it's not just important to go to the doctor and get recommendation based on an ‘average’ human being—but it is way more important to get targeted recommendations, when we have knowledge about people from our own sex, our own demographic, our own age. Age is important in how we metabolize and respond to drugs. And we don’t know how we each respond to drugs because none of us is an ‘average’ human being. The only way to know is to measure it.”

We’re obviously big fans of measuring over here! It's what powers our products, like InnerAge.

“And that’s what I love about InsideTracker, is that you know based on data whether something is changing, rather than just guessing and hoping that we are all close to being similar to the test subjects in clinical trials. Many times we are not. We differ in our hormones, in our genetics. Women have a whole extra X chromosome. Men have a Y chromosome. That’s a big genetic difference. We have different bugs in our gut, we lead different lives. And that is why the future is all about individual measurements, and tailoring lifestyle, supplements and even medicines, for each one of us.”

To stay on top of the new developments in the field of aging research, be sure to check out David's Lifespan newsletter and blog featured on his website.

* Disclaimer- David is an investor and Chairman of InsideTracker's advisory board, click to learn more about David A. Sinclair's affiliations.