Episode #120: Dr. David Sinclair: ‘Why We Age & Why We Don’t Have To’

Today, my guest is professor of genetics and anti-aging at Harvard University, Dr. David Sinclair.

We dive into simple ways through lifestyle and supplementation to turn back your biological age. He also shares some new discoveries and exciting news that you can learn from him each week on his new podcast LIFESPAN. Every time I see David, he looks a few years younger, so he walks the walk. I love seeing him and learning about all the helpful information they discover in his lab. We can’t fight time, but we can be proactive in slowing down our internal age. Enjoy.

Listen to the episode here:

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Key Topics:

Dr. David Sinclair: ‘Why We Age & Why We Don’t Have To’

My guest is Dr. David Sinclair. He’s a professor of genetics and anti-aging. He has got a lab at Harvard University. He wrote an incredible book called Lifespan. If you haven’t read it, I would suggest getting it. It’s the best textbook. He’s talking about turning back your biological clock. Something’s working because he looks younger and younger every time I see him.

He also has a new podcast out called Lifespan and you can listen to it wherever podcasts are broadcasted. He takes a topic and talks specifically about that topic for one hour. He gives you the science on it and he breaks it down. If there is anything actionable you can do in your everyday life, he shares that with you. He makes it comprehensive.

He also shares what he’s doing in his own life. Right now, he is eating vegetarian, he’s lost weight, his numbers are better. I love David. He’s so intelligent. His curiosity, his playfulness, and he’s there to share, “Can we age better? How do we turn that internal biological clock, either slow it down or even reverse it?” I hope you enjoy.

Dr. Sinclair, thank you for coming. Welcome.

Thanks for having me here.

You’ve been here before and we’ve done interviews before, but this is the first one in person. I hope you’re not offended if I just refer to you as Sinclair because that is the most endearing way I could call you. I respect that you’re a doctor and your lab is at Harvard, but you’re a teammate.

What’s wrong with David?

Because you’re a G. You should be referred to in that G way.

David is too common. Sinclair’s good.

You have a new podcast out, Lifespan with David Sinclair. I was thinking about you and Huberman and you’re like the science mafia. He’s a teammate, too. You, Huberman, and Walker are this unbelievable group that is exchanging expertise and information, and now you’re the cool kids in school. How’s that going?

I don’t know if we’re the cool kids in school, but we are the rebellious ones. We have the FuGENE in abundance. Andrew and I spoke at the beginning of the pandemic and we decided to communicate science because we saw a gap. When the pandemic happened, people didn’t know who to trust, what was real, what’s scientific, what’s made up on the internet. We both identified that so we’ve stepped up. So far, so good.

I love the way Andrew Huberman talked about it, which was public education. I thought that that summed up this idea of ivory tower knowledge, which you all have. He’s at Stanford and you’re at Harvard. You have found a way to break it down, to communicate, to share it, and to make it actionable, which is hard. We’re going to try to dumb it down even more here.

That’s going to be hard, but I’ll try.

If the data is there, you can dumb it down. I’m curious as somebody who is fond of you, this is a life change. You’re getting pulled in more directions now. You’re not going to get away with just talking about slow and anti-aging. I want to know how you’re managing these additions to your life because people go through changes all the time.

You know way too much about me and my personal life so we’re not going to go there.

We’re not going to go through all that up on the table. I’m just saying, with these new demands on you…

It’s a serious thing. You make time for what you think is important and you deal away with things that are not, so that’s what I do. I have a hierarchy. Things fall off the bottom and they’re not that important. What’s important first and foremost is my children, of course, but then in my career, it’s my lab and then the companies that I work with. Communication is becoming increasingly important. Those are the three main pillars of my career.

Every day is busy when you’ve got all that going on. Running a lab at Harvard is supposed to be a full-time job. I do this other stuff because I tend to get bored easily with just doing one thing every day. It’s an ecosystem that’s working well. I didn’t know how it was going to work out. Andrew and I could have been kicked out of our respective universities here at Stanford and MIT Harvard for doing this.

It’s unprecedented that scientists at our level have become public communicators, but it’s working out well. The ecosystem for education is great. I’ve got my book, which you’ve kindly said nice things about. Thank you. That was my first foray into hitting large amounts of people. Hundreds of thousands, close to a million now around the world have read these words, sometimes multiple times.

It’s a workbook. You’ll get to textbook. We’re going to talk about a lot of things. A lot of it is in the book and it is a resource, so Lifespan can be used that way.

Thanks. I put a lot of effort into referencing like Andrew does. Whenever you read a fact, you can look it up to see if I’m lying or not, but not that I would. It’s important to the two of us that we are seen as truth-tellers. We don’t say anything that isn’t backed up. If we don’t understand or don’t know something, we’ll say so. That’s what’s missing in public discourse. People pretend that they know or say it as if they do know when they don’t really know.

Most people have never read a scientific paper in their lives, but they’re out there saying, “You should do this.” It’s not often their fault. Unlike Andrew and I who have access to the world’s libraries of information through our universities, what regular person has that? It’s beyond most people’s reach and who has the time to read it. It’s our job to read it. That’s what I try to do.

The ecosystem of the book, the podcast, my lab, and the companies are working out well to achieve my mission, which is on my mind every day, which is to leave the world better through the highest impact of what I can do to slightly bend the needle. When people say, “Why are you doing that? Why would you ever podcast? Is it for ego?” No. Like Andrew, I want to serve. I want to change the way people see their lives and give them information to improve it.

You personally are a good example. I’ve known you for a few years and you are definitely Benjamin Buttoning it. Right now, you’re as lean as I’ve seen you. I know you’re busy and you’re probably not getting enough self-care, but you keep looking fresher and younger than the last time I saw you. The other thing that I like is that you experiment on yourself and talk about your own practice. Different from Huberman, you still live more like a normal person. I don’t think you’re a huge fan of exercise. You like your red wine. Huberman is more in the church a little bit, if you will. I appreciate that you have a balance of that.

I’m lazy, in general. I don’t like working out. In your pool, I suffer badly. As you could tell, I had a few gulps of water on occasion. I like food. I like mea. I like alcohol. I like having a good time. I like tasty things. I’m a foodie. I’m not perfect. Sometimes people say, “I saw Sinclair, he ate an egg.” It’s like, “Food police, I’m not perfect.” I do try not to eat a lot of sugar. I try not to eat a lot of meat. I’m currently experimenting with a vegan diet to see what it does to my body.

I saw that and I saw the woman that’s inspiring you to do it, Serena Poon. There is a lot of data showing, “If we can minimize the amount of red meat and lean towards vegetables,” we all know that that’s a good idea.

The sciences, that’s all that matters.

I understand how you did that. It’s funny how you get attached to these things. I personally can get attached to eating a certain way. “That’s how I eat. What am I going to eat?” How did you think, “I’m going to experiment with this.” Did she help you? Did you feel like there was a roadmap on how to do it and you felt ready to do it? How did that come about?

That’s a good question. I have never answered this question.

I feel like you don’t answer a lot of questions.

I will be truthful. You can ask me anything. Usually I answer this, so truth serum today. How about that for Gabby?

I’ll keep it mint light to serum light.

What happened was, I’ve been changing my diet over the years to try and be better. I’ve had relapses into a bad diet where I’m eating pizza and French fries because I’m stressed out. This is in my 30s. In my 40s, I got more serious. We all do. We see the end and we think, “I abused my body in the last 10, 20 years.” In my 40s, I made the strict decision not to eat dessert. I steal little bits and that’s enough for me. That made a big difference. I cut out sugar.

I’ve had a tendency to be overweight. I was overweight as a kid. I lost it when I discovered girls in college and I’ve tried to keep it off, but you’re right, I’ve never been this lame. It’s a story about how I’ve been evolving my diet. What’s important about what I do is it’s science-based. It isn’t, “I look better,” or, “I feel better.” I measure the numbers. Often, they surprise me that they either went in the wrong direction or they went the right direction. If you just base it on how you feel, that’s not good enough. You have to look at the numbers.

[bctt tweet=”Who cares how many times the Earth has gone around the sun? That’s irrelevant. Your age is malleable. You can go forward quicker. You can go backwards. That’s important. That’s a credit score for the body.”]

I know you’ve invested in this company, InsideTracker. I heard you referenced on your own podcast that you don’t drive a car without a dashboard. You’ve even talked about getting numbers back that were not favorable. Sometimes people are scared to look under the hood because they go, “What am I going to find? I don’t want to know.” That’s normal. I experienced it. I would imagine I’m healthy and other people are probably feeling this way.

It’s important to highlight the fact that you have had blood work that you thought, “It could be a lot better,” or, “It’s not great.” The fact is, it’s way better based on some of these changes you’ve made and the consistency of that, even your internal age or your biological age. In talking about that, if you could share a simple way where people could say, “I need a starting point. I need a reference,” and not to be afraid because we can change it.

80% of our health in the future is in our own hands. Only 20% is genetic. That should be empowerment. Knowledge is power. Ignoring it is not going to fix things. You have to fight the urge to be ignorant. Ignorance might be bliss, but it’s going to come back and bite you in your old age or sooner. There are times when I don’t take the test because I haven’t eaten well and I’m not going to get the right numbers back.

You’re going to catch up.

You want to read the numbers a little bit. Everyone’s human. I tend to take the test when I know I’m going to get some decent numbers. I take some supplements and I try various things because I’m an experimenter. I’m trying to help people and I’m a guinea pig for their benefit and mine. Numbers come back and they’re bad. I might hurt my liver with a supplement or my cholesterol has gone the wrong direction or my testosterone has decreased.

What I do is research it. I have a team of researchers. Not at Harvard, but I pay them outside. They will science the crap out of these deviations and say, “There’s a study that shows that if you do that, it’ll correct that.” Then I do that and see if it works. If it does, I keep doing that. That’s been an evolution of my life in optimizing my body and I’m happy with how it is.

I have to ask the magic T question. Every man on the planet is interested in testosterone levels. It’s just the way it is. What things were you finding boosted that?

It was a combination of things. It wasn’t just doing one thing and suddenly it doubled. We will get back to Serena and her recommendations on food. I might focus on testosterone for a while and try to fix that. I was hovering around the 200s, 300s which is low for a man even in his 40s. In my mid-40s, I was like, “I got to do something about this. I don’t want to lose muscle. I don’t want to have no sex drive.”

No libido is a bummer.

The first thing I did was I started building up big muscles in my body, so leg muscles, hip hinge exercises for my back, deadlifts. I built up big muscles. I’m not a big guy, but it made a difference suddenly. Over those two years, I went from a 200, 300 number up to about 500. I was happy. I was mid-range for someone my age. It’s not a lot. I wasn’t a super testosterone man, but I was okay. I wasn’t losing muscle, at least.

I understand growing big muscles and what the impact of that is, but maybe you could explain a little bit because someone might go, “What’s the difference between overall body exercise and building up those big muscles?”

Research has shown that the bigger the muscles in your body, the better effect on your testes to produce testosterone. I don’t think it’s fully known exactly how that works other than it does and I certainly saw that. It was mostly the recommendation of my trainer, Shawn. I said, “Here’s the problem.” I showed him my InsideTracker results and he said, “We’ve got to fix that testosterone.”

He was not concerned about your cholesterol. He’s like, “Let’s talk about your testosterone.”

At the gym, that’s the hormone of interest usually for men. I’m at a point now where it’s been steadily going up. After I did the exercise, I started taking higher amounts of NMN. I’ve been on NMN, which is this NAD precursor. Readers may know about this. I know you know about it.

Because of you.

We’ve been researching the role of NAD in the body for years. It’s been known for 100 years to be involved in energy metabolism and reactions in the body. It’s a little chemical that we have probably 100 grams of it in our body. We lose the ability to make it as we get older. What happens is that the defense enzymes that keep us young that we study called sirtuins, which we have seven of these enzymes in every cell, don’t work without NAD. The idea is to raise those levels back up.

For me, if I was an average 52-year-old, I’d have half the levels of what I had when I was 20. I supplement within them and get the NAD levels up high, and they get to work. Myself, my colleagues, other labs, over the years have shown that in animals and some results in humans that will be coming out, these sirtuins protect the body against things that cause disease in aging.

For example, they boost DNA repair, they boost endurance by improving blood flow, they protect organs when they’re damaged, and they keep the animal’s tissues younger. We have a study with hundreds of mice that we’ve been running for a couple of years now. Those mice have less frailty, better body shape, better metabolic flexibility, which is important, and look like they’re going to live on average longer than the ones that aren’t drinking the NMN water.

Why do I mention NMN? Because my NMN dosing went up to a gram a day and that gave me another boost in testosterone. When you look in the literature, we and another lab studied a protein called SIRT2. It’s one of the sirtuins. SIRT2’s job isn’t to make endurance better, but to protect the DNA of the body when cells divide. There are two things that it’s good at. One is that it helps female eggs be younger. We’ve shown that if you give NMN to old mice that are infertile and the equivalent of a 65-year-old human, they can give birth again because their eggs are healthy.

I have been taking this because of you, but that might stop. I’m not sure. Can you imagine if I had that conversation with Larry, “I need to tell you something.”

There are people who are betting that this is going to be true in humans as well. We have some data on a small number of horses that reversed their infertility. It’s probably going to be true for people, though we don’t know. We have to do placebo-controlled trials. The other thing that SIRT2 does that’s relevant to this conversation is it controls the production of anabolic steroids, testosterone, estrogen, progesterone. It makes sense that what I saw was true for my testosterone being regulated and it also makes sense what we saw in the mice.

I have a question, and then we’re going to slide over to your diet change. I’m taking it, coupled with a couple of other things. For people who aren’t going to take metformin or something like that, or maybe they can’t get their hands on it, you make a suggestion on a couple of things that people can take that can support their aging, but also the best way to take it. I take it in the powder and I just shoot it, but it’s not the best-tasting thing. Can I do it on an empty stomach? What is the best way for you?

Is that with NMN?

Yeah, and the resveratrol and berberine. Is it separated? Is it together? How much in the morning and night? How do we do it?

We can run through my daily life if you want.

GRS Sinclair | David Sinclair

David Sinclair – I’ve been an educator. I like speaking to people. I like educating them and they go away with knowledge. This is how I get my pleasure.

The more I can talk about you, the better. Do you feel the resistance? I like scientists because they’re like, “We’re talking about the data.” I’m like, “No, we’re talking about you, too.”

We work for institutions that are conservative. We push the limit when we talk about this stuff because everything’s supposed to be clinical trial-proven. I’m happy to do it. I have this FuGENE that I talk about.

In the end, it’s about doing the best work possible. Somehow being at Harvard makes people feel comfortable. In a way, being able to straddle that is more impactful.

That’s why I’ve been doing it for years and honestly. Several years ago, to talk about supplements, what I do, and age reversal was not a good look among my colleagues. Now it’s more acceptable. There are some main components to what I do that have helped my testosterone and other markers. Most of my blood markers are equivalent to or better than a 20-year-old from optimization. I say that to inspire people that it’s doable if you look at the numbers and tweak things.

What do I do? I wake up. I’ve had a bed that’s been monitoring my heart rate, so that’s fun. It usually vibrates to get me out of bed. It warms me up. I stumble out of bed. What readers like to know is what I take. I start with a matcha these days. I also have the coffee that you’ve been giving me. It’s one of those two. I’m drinking yours right now. It’s great stuff.

Let’s start with supplements. I start with a combo of resveratrol, which is the molecule from red wine that we talked about and discovered was important a while ago. The red wine story is good for you. I’ve been taking that since I was in my mid-30s. I take that with a little bit of yogurt. For the aficionados who are going to say, “That’s breaking a fast.” I have to dissolve it in something because otherwise, it sinks to the bottom of the coffee or the water that I’m drinking.

It has an almost filmy feel to it. It needs to get into something.

It won’t be absorbed by the gut. It’ll just go straight through you. Here, I can speak with some scientific data. I know from clinical trials that if you mix it with something oily, eat it with a meal that’s got a bit of fat in it, which is what we did to the subject, it was better, those fivefold levels getting into the bloodstream. I do that and I make some other polyphenols as well. There’s one called quercetin and fisetin. We discovered those three molecules extended the lifespan of model simple organisms back in 2003 and ‘05. That’s a little-known fact that I don’t talk about.

When you’re in the lab and you’re learning all this stuff, the way you’re able to interface with the public, I don’t want to say it must be frustrating but it’s like, “I know some stuff. I could help some people.” In a way, there’s probably a system. This must be fun for you to be able to say, “We have the science, but I can also interface with people.”

What I appreciate about your podcast is you’re being specific, breaking things down, and supporting those concepts scientifically chapter by chapter. I feel like each one is like a chapter. You’re doing that well, but it must be fun that you can be like, “They can listen, they can go get it, they can start. It’s not years and years.” It’s cool.

I spent many years talking to the public through newspaper reporters and that’s useless. This world that we’re in is so great because I can speak directly to people, get even feedback on Instagram Lives and that kind of stuff, and direct messaging. My dream is to be able to help people because what I was doing for a couple of decades was making pharmaceuticals which take forever. I got a bunch of them in the works. I want to help people immediately. I was helping friends and family. Most people know my father is on the protocol, too. I want to reach millions because it’s not that hard to change your trajectory.

You can live an extra fourteen years just by doing five things that I’ll tell you. It’s shown that if you avoid smoking and drinking heavily, get enough sleep, eat in moderation, and tend towards a Mediterranean diet, not a lot of crappy fats, you will live fourteen years longer than someone who doesn’t do that. That’s the easy stuff. That’s what we know. The stuff that I’m talking about, the biohacking stuff, through supplements, diet, exercise, some other tweaks that we should get to, why couldn’t that be another 20, 25 years over what is the average lifespan? That’s what we’re talking about.

Equality, too. In your podcast, you talk a lot about cancer patients. There are a lot of layers to this. This isn’t just like, “My skin looks better.” There are a lot of health layers to this. You do your resveratrol and your yogurt in the morning.

Let’s do that list. Disclaimer, I’m not a physician so make sure your physician knows what you’re doing so that if something goes wrong, they’ll know about it. They might even advise that you taking this medicine is not compatible. That’s important to know. That’s not just a disclaimer, that’s a health concern. Always consult your doctor.

Resveratrol, a gram of that. I have buckets of resveratrol in my house. If you keep it in the dark, dry, it’ll last for decades. I’ve had that material since we did clinical trials on people. I’ll scoop a few teaspoons of yogurt these days because I’m going more plant-based. It’s coconut-based yogurt, but I used to have Greek yogurt. Both work beautifully.

I also put quercetin and fisetin, which are all three plant molecules that plants make when they get worried that they might die. The theme of this is you want to have your food scared that it could die. You mimic adversity. Your body, the same, its body freaking out it could die next week from either lack of food or getting chased down by a saber-toothed tiger, too hot, too cold.

Same with your plants, these molecules plants make, we don’t make them. My theory is that by eating these plants, they’re stressed out and worried they’re going to die. We get the benefits of those molecules that they’ve made to help themselves, but they get into our body and turn on our own defenses and mimic adversity. They mimic exercise. I’ve told you NMN already, but resveratrol also mimics exercise because it turns on the same things as actual exercise. That’s resveratrol, then I do my NMN, which is another gram that I put in capsules that I don’t buy on the internet.

Is there a brand that you feel comfortable saying?

I’m trying to be helpful. To be open about it, my name gets used a lot on the internet and I don’t need more of that. If I mentioned a brand, it’s going to be splashed all over their website.

If there’s a brand that you’re invested in or you own, it doesn’t matter to me. If we’re promoting you, I don’t care.

I don’t sell supplements because I want to be objective and independent.

What needs to be in there to know it’s good?

Resveratrol should be a light gray powder, dry and fluffy, and not sticky and brown.

It’s chalky.

It’s so hydrophobic. It loves things that are not wet. It’ll dry your hands out if it gets on there. That’s one of the problems, it doesn’t go into water. It hates water. The resveratrol should be light gray. If it’s brown, throw it away because a lot of manufacturers cheat. They put a little bit of resveratrol in there and they don’t purify it enough.

There’s a mode in a molecule that causes diarrhea. I hear from people, “I’m getting diarrhea with my resveratrol.” If you’re getting diarrhea from resveratrol, throw it away. NMN should be even whiter. It’s pure white, crystalline, not so hydrophobic. In fact, it loves water. If you put it in water, it’ll dissolve within seconds. You can have your NMN without yogurt. You can just drink it or swallow it.

Can you do it at the same time or do you like to spread them out? Would you be comfortable if I had brands that I like that I think are good? Would it be okay if I say what I’m taking in my show notes?

Of course.

[bctt tweet=”I prefer to preserve what we have rather than replace it. Usually, the replacement is not as good.”]

I’m not going to make a suggestion. I will just say the ones that I’m taking.

Do you know what’s going to say on the website? Sinclair’s friend, Gabby Reece. You should because it’s not fair for me to say, “Do this,” and I can’t steer people in my direction.

I see the conundrum, but it’s hard because people want to know. The funny thing is if you’re putting the extra time and resources into something, then people want to get the good stuff.

You can look for the color. One tip that I can tell everyone that’s important is if you’re taking a molecule, let’s say it’s quercetin, fisetin, resveratrol, NMN, you can look up on Google what color it should be. It’s listed as a scientist would see it. Quercetin is yellow. Fisetin is a brighter yellow. If it’s supposed to be yellow and it comes out brown, throw it away.

Wrong stuff.

Look for companies that use the letters GMP, Good Manufacturing Practice. At least then you know it’s not contaminated with stuff and it doesn’t have metals in it. GMP is good. Brands that have been around for a number of years, trust those. Not these fly-by-night folks that come out of Florida every few months.

Where there are tan doctors somehow.

One thing that’s important is if a company is using my name, avoid those companies. That shows that they’re dishonest, to begin with.

Dr. Oz had a lot of that, too.

The three of us had to deal with that. They’re more than me.

Are you still taking metformin?

Yeah. That’s my holy trinity. A bit on metformin. Metformin is a drug. It’s a molecule that is related to a plant molecule. Plants are good. It’s classified as a drug, but it doesn’t mean it’s any scarier than this other stuff. It’s just a different regulation in this country. What’s funny is if you go to another country, mostly in Asia or Africa, you can buy it like aspirin. It’s not considered a toxic drug. You should tell your doctor you’re taking it no matter what.

In the US and English-speaking countries in Europe, you need a doctor’s prescription to get metformin. What is metformin? It’s used to lower your blood sugar levels. It’s given as one of the first drugs, if not the first drug when you have Type 2 diabetes. How it seems to work is it will trick the body into thinking it doesn’t have enough energy. The body will build up its ability to utilize energy and suck the glucose out of the bloodstream into your body better. That’s useful, but it’s also been shown by looking at tens of thousands of patients who take metformin that they’re healthier in general. Those patients live longer than people who don’t have Type 2 diabetes on average.

Doesn’t it feel unfair to you somehow? Based on your lifestyle, you’re doing the right thing and they’re like, “Sorry, you can’t get that because you don’t have Type 2 diabetes.”

My poor doctor, I rail on him. They’re my doctor’s view. I won’t say all doctors. There’s a prevailing view that we intervene when you get sick. That’s what doctors do. Don’t come to me now saying, “Give me metformin to prevent diabetes.” That’s not what we use it for. I’m insistent saying, “Give it to me now. I need it.” Some people have been insistent with the doctors. They’ll give them a copy of my book or give them papers that are referenced in the book. I’ve heard that that can help doctors. There’s also an online company that you can google to get it directly from the company. If you can’t get metformin, there’s an alternative called berberine.

That’s what I take. It’s yellow.

It’s bright yellow. It’s also one of these polyphenols from plants that don’t dissolve well. Do you dissolve it in something?


There you go. I would recommend it. I don’t know if it’s a problem.

Is polyphenol weirdly good for your skin? Why do I know this from another thing? I’m trying to remember.

I’ve patented stuff that’s used on skin with polyphenols for a while, so this is one of the things that I put on my skin. A phenol is a ring of carbons with some hydrogens on it and a polyphenol is multiple rings of carbon rings. Let’s talk about resveratrol. It’s two of those rings fused together with bonds. It’s not rocket science. These polyphenol plants, in response to adversity, if you restrict their water or give them a fungal infection or too much UV light, make these polyphenols as a way to turn on their own defenses. Plants have sirtuins like we do, the ones we study.

I don’t know about their fertility if they’re affected. They don’t run. It’s all about adversity and survival. When we take these polyphenols in combinations, what they’re doing is telling the body two things. One is, “Maybe I went for a run,” or, “Maybe I’m hungry.” What we’ve done is we’ve evolved to sense when our plant supply might be running out. How would you know? For most of our evolution, we weren’t conscious, we were dumb.

Our bodies were sensing the chemicals in our food supply and hunkering down, getting ready for adversity when the plants that were eating were stressed out. That’s the idea. Berberine is one of these polyphenols that is soluble in the plant but during the extraction process, ends up being this hard crystalline, hydrophobic, poor to dissolve chemical that you need help to dissolve using either yogurt or olive oil. Those are two good things that I use.

That’s good. It changed another practice of mine. I respect the straddle, but is there any other supplement stack or anything else in observation that you like?

Yeah. In my book, I’ve written down a lot of it on page 304. People can go to the cheat sheet. I would try to read a few other pages because it describes why I do what I do.

Do you still like spermidine?

I’m taking spermidine, but that’s post-book so that’s not on the list.

We still haven’t gotten to your diet, but we will. I want to go with what we’re talking about. Off the top of my head as a layman, sometimes there’s been talks about what’s tough eating certain plants or vegetables. They do have this stress response and they are defending themselves. That has also been flipped and interpreted as making it harder on us. I want to say that because a lot of times you’ll hear, “Plants are defending themselves.” I’m bringing it up because people are like, “I heard this.” I want to say that that’s all part of what people are hearing.

In my research in the thousands of papers that have been done in parallel or in general, not every molecule, there are some defense toxins that plants make. In our food supply, the kind of supplements that I take and the plants that I eat are the ones that make these beneficial polyphenols. I’m not afraid of colorful stressed-out plants. I try to eat organic so that they’re not grown in a hothouse so much and they might have had a bug or some trouble growing.

Matcha tea is a good example. They grow the green tea in shade before they pick the leaves. That’s adversity, lack of light, not too much light. I look for colorful foods because the color comes along with these polyphenols. You can’t see resveratrol in a plant. It’s colorless, it’s gray, but you can see the colors. Let’s say if I go to the vegetable section of a supermarket, I won’t just pick light green food like lettuce or watery lettuce. That’s not going to have these molecules in it.

I learned that you’re a big fan of kale.

The worst. I don’t know why we eat that stuff.

GRS Sinclair | David Sinclair

David Sinclair – The ancient Greeks to me is ideal. They weren’t massively built. They were lean and fit and slightly muscular. That to me is longevity.

You’ll hear over and over, especially for the microbiome, “Diversity, diversity, diversity. Eat the colors of the rainbow.” I appreciate you bringing that up. A lot of people are familiar with lifespan. They have a lifespan. Science is always moving, it’s changing, and you’re learning something new. We brought up spermidine. What are the things that you’ve pulled out that you go, “This is important, too,” since the book?

I take spermidine because it protects the inflammation in the cell that keeps us young. It’s called polyamine. My theory is that we age because the cells lose the ability to read inflammation. That’s what spermidine is doing and the reason I take it. It does something else that’s related. It turns over all proteins and recycles a protein called autophagy. That’s the process. I’m trying out something interesting called alpha-ketoglutarate. It’s a ubiquitous molecule. It’s used by cells in what’s called the TCA cycle. It’s a common chemical. You’d never think it would prolong life, but it definitely does in mice.

What led you to look at that?

We had the theory that it was controlling the body’s clock called the DNA methylation clock, which we can measure now.

Is that the Horvath?

It’s the same. If you give alpha-ketoglutarate to cells, it changes the clock in a beneficial way. It was an old, longtime colleague of mine and friend, Brian Kennedy, who trained with me at MIT in the ‘90s. He taught me how to wrangle a yeast cell and look how old they are. Brian did these studies here in California at the Buck Institute and what he found was alpha-ketoglutarate kept worms alive for longer. Then he gave it to mice and they lived longer. There was a study that came out that blew my mind and it’s still hard to believe. They need to reproduce it. I have talked to the people who did the study. I usually do that. By the way, I don’t just read the data. I call them up and say, “Is this BS? Seriously? This is too good to be true.”

From one scientist or another, you can call them up and go, “Come on.”

Yes. I did that with most of the studies that I find.

What country was this in?

This was done in the US. The latest study is being done in Singapore. It’s rigorous. Here’s what blew my mind. This paper said that people who are given AKG, alpha-ketoglutarate, for seven months, Horvath clock measured before and after, and they were eight years younger.

Did they change any other elements of their lifestyle?

Not that it says in the paper.

Were they all of a sudden running marathons?

No, of course not. They tried to keep things stable.

Everything is consistent.

Where it could go wrong is that their math is a little different than what we typically use. That’s what I wanted to know. “Why are you using fuzzy math or different math for this?” They said, “We have our own proprietary algorithm.” “Can you use the same ones as us so we can compare?” They’re going to do that. I’m interested enough that I’m now taking it. We’ll see. I’m measuring my age often.

InsideTracker has where you have the actual and then your biological. That is one way. When people hear about the Horvath clock and you’ve talked about it before, are we able to measure that for ourselves?


Is that available or is it going to be available?

I’m working on that. I have this startup that’s come out of my lab called Tally Health and it’s backed by some big consumer brands. They’re the kind of people that can get these tests into millions of people’s lives. Part of the problem is that most people don’t realize that this clock exists. You can measure it and you can do things about it to slow it and reverse it. That’s the message here. We’re working on developing this. I’m younger than I used to be.

I know you are. I’ve seen you. You and I are the same age. Next time I see you, they’re going to ask if I’m your mother and then the way we’re going. When I say I’m going to talk to you, they want to know, “Do I get access to the Horvath clock?”

It’s coming. It’s a blood test right now, which is expensive. It’s hundreds of dollars and it takes two months to get a result. There are some groups that are doing that. One of my students figured out a way to bring the price down a hundredfold in the lab. It’s going to be a cheek swab, not a blood test. It’ll tell you with accuracy how old you are biologically, not chronologically. Who cares how many times the Earth has gone around the sun? That’s irrelevant. Your age is malleable. You can go forward quicker. You can go backwards. That’s important. That’s a credit score for the body. There’s a website if people want to stay in touch. When it’s ready, you can be the first one. It’s TallyHealth.com. Sign up there.

Then they’ll get information once you get it?

Right, and even updates. We were even thinking of doing pilot studies with people who are the first to sign up and of course, discounts.

Justin and I can talk to you about this. We’ve been talking about NFTs and all this stuff. Dr. Sinclair should definitely get into the NFT space. When you get all this other stuff done, we’re going to have some fun. It’ll be amazing. Let’s switch now to being a vegetarian because this will lead us into the conversation about fasting, eating once a day, where you’re at, and what made you decide, “I’m going to give this a go.”

I’m coming from a place where most people are, which is I love food and I love meat. It tastes great. I love fat, I love French fries, I love cake. Cheesecake is my favorite. I say that because I’m only human. I’ve managed over a matter of years to get to where I am now and it takes some willpower. If I can do it, seriously, anybody can do this. That’s my take-home message.

What did I do? I stopped eating dessert at 40. In my 40s, I started to eat better and better. I tried to avoid large amounts of meat. I didn’t have big steaks. I got to a point in 2021 where I was not eating more than 1.5 meals a day. I was eating what you call a Mediterranean diet. I was okay eating fish. I would eat red meat. If it was an animal that was walking on its legs, it would be a chicken. I would eat a lot of vegetables, which at the time, I didn’t know how to cook or eat conventionally.

Do you cook?

I do. I do like that. Molecular biology is cooking. It’s just on a small scale. I like mixing stuff and seeing what happens.

Do you plan ahead?

No. That’s one of my problems in life. I don’t plan ahead enough. It drives people nuts. I just see what’s in the fridge and I make stuff up and hopefully taste okay to my children and me. Usually it’s okay. I’ve been tending towards more and more vegetables over the years, but I got bored. It was salads and it was steamed vegetables, which is not that exciting. I met Serena Poon. She’s a celebrity chef and a nutritionist and she says, “You can have great-tasting vegetarian and vegan meals.” I’m like, “Come on.”

Did you move in and now you have the beautiful and talented Serena Poon making your meals? Because it does take someone like that to switch your thinking about how you can prepare these meals. She met you and said you can do it, and then what happened?

It took a few weeks of convincing. She would keep reminding me of the types of foods that I was eating. I would give her a call and she’d say, “What are you eating?” I said, “For dinner, it’s a bunch of cheese and some red wine.” She’d say, “David, that’s not going to make you live longer despite what you think.” She was on my case about that because I would not have the longest living lifespan a diet would be.

Eventually, I was convinced by her that she was right in what she was telling me. She knows her stuff a lot. This is my hobby, it’s her life. She’s been trained at some of the best schools in the world. I haven’t told anybody this. What happened to me was I went to dinner with one of the most influential, richest people in the world. I won’t say the name because I don’t think they’d appreciate it. They gave me a lot of food. The hosts were generous and gave me a fair amount of red wine as well, good, high quality. If it’s a few thousand dollars a bottle, you don’t just say, “No, thanks.”

I had a bit of a Bacchanalia festival over this side of the country, so I woke up not feeling that great. I talked to Serena about what had happened and she said, “This is not good for your long-term health. In fact, I can tell you’re losing your ability to remember things.” It’s true, I was starting to forget things. I thought, “Either it’s old age or it’s my lifestyle.” I can’t as easily change my age as I can my lifestyle. I decided around that time to stop what I was doing. I went vegetarian, and then shortly thereafter, vegan and I stopped alcohol. I liked doing that strictly because I don’t like making decisions. It’s more about, “This is the rule. We’ll see what happens.”

I call that the breadbasket rule. A lot of times, I will try to skip meals. If it’s lunch and maybe it’s been a robust day so I’m extra hungry, I will make the pre-decision that I won’t touch the breadbasket. If I haven’t consciously made that choice, when they put the bread down in front before you can get your dinner after that, I would mindlessly eat it. It’s these hard rules. That’s important. Most of us can’t decide on the fly. I always say to people, “It’s not that you can’t. It’s just that you don’t.”

[bctt tweet=”I want to change the way people see their lives and give them information to improve it.”]

For me, it’s not a hard rule, but it is a rule. I break rules.

It’s a guide most of the time. It’s like, “If you’re going to go do something special or you have a celebration, fine, but this is what I’m doing.”

That’s the key to success. If you’re too strict and you’re sitting there going, “I want that bread,” you’ll eventually fail and say, “Forget this.” It’s okay to treat yourself. Otherwise, what’s the point of living longer anyway?

What about the alcohol? Has that been hard? No offense, you’re an Aussie. It’s almost like it’s somehow in the DNA. What’s interesting in our world is there is something wrong with you if you don’t drink alcohol. I have no moral issue with alcohol. If people want to drink or whatever people want to do, I just don’t. I grew up in the Caribbean and everyone was drunk all the time and you’re like, “This story does not have a good ending.”

With Laird, it’s well-documented. He dealt with alcohol for the first ten years of our marriage. You do talk about, “If you’re going to do it, Pinot Noir is the way to go.” Laird understood that from a health point of view, so he drank bottles of Pinot Noir. He said, “This isn’t serving my life.” What’s interesting is you go places and it’s harder for guys than girls that it’s like, “What’s wrong with you? You’re not drinking. You don’t drink? You don’t want to drink?” How did you deal with all that? It is a weird social thing. You probably have to go out, go to dinners, and see people in business and all these things.

You’re right, that’s the hard part. Being vegetarian and vegan isn’t that bad unless you go to restaurants and they say, “We don’t cater for you.” That’s the downside. In California, it’s rare. In Boston, it’s like, “What? You don’t want steak? You don’t want ribs?” Alcohol was socially a problem. Probably half the people that I socialize with roll their eyes and go, “Sinclair, again?” “Another one of his fads.” “Now it’s not alcohol. Now he’s not going to be funny anymore.” I’m not as funny as I used to be. I thought I was funny.

Have you ever been sober with a group of drunk people? It is the worst thing ever. You’re like, “You guys are not that funny. I know you all think it’s funny, but it is not funny.” The problem is if I’m doing something that maybe I know ultimately isn’t that great for me, I need you to be on the same program with me so it’s more fun because otherwise, you’re a reminder of what I’m doing. It’s almost like a contrast at the moment. People always get the trick of bubbly water with a lime in it and maybe a splash so it looks like it could be vodka. Do you do that?

Yeah, I do exactly that. I hang out with people who have wine collections on occasion and that’s where it’s hard. “I brought this bottle of wine,” or, “I brought this from the cellar.” That happened with the alpha-ketoglutarate, AKG group. I smelled it and I sipped a little bit. We can break rules on occasion, but I don’t drink like I used to. I wouldn’t say it’s excessive, but it was constant. Most nights of the week, I’d have a glass, maybe 2, maybe three.

If you do the math, that’s 10, 15 a week.

There are calories, too.

Also sugar.

The result is that I’ve got my memory back, I’m clear in what I think, I can make decisions better, and I’m talking quickly. It’s been hugely beneficial to switch this diet. My blood numbers from InsideTracker have never been better in my life, even when I was starting this program.

You were jumping on that horse to get that test. You wanted to get a good report card?

I didn’t. I posted this. Anyone who follows me on Instagram would have seen that I have this meter that says how old I am based on this InsideTracker test. Did you see it?

I saw it.

I got a bit of heat from that from people saying, “Stop showing off.”

It’s a good reminder that people have to remember that they have more control than they realize, but we have to do it. It’s not just going to happen. Yes, you can go to the doctor and they will give you pills but, in the end, it’s a great reminder of finding your reasons why, creating a plan, and also having people around you that support those decisions. That’s how I took it, but everyone has a different perspective.

A lot of diets fail because people around you are like, “Come on, eat that. Come on, drink that.”

Feel bloated and crappy like me.

Be funny like me. I’m turning 53 in June 2022. That test was the best ever.

How long ago was the first test that you did? Do you remember?


In 10 or 11 years, you’re coming out with the best test.

I’m a decade younger than my chronological age based on their algorithms and I posted it. The company wrote to me and said, “Those are amazing numbers because our algorithm only lets you go back a certain amount and you start to hit a wall, which is about ten years.” They said, “Would you like to see how you match other people who are 52 years old in our database around this age?” Of course, I’m going to say yes.

Because you’re like, “I like to win.”

I got the graph and it’s a distribution. Most people are 52 around my age as you might expect biologically and there are a bunch of us. It tapers off down with a tiny thin line down to people that are 42.

What you’re feeling is that you are probably younger, it just wouldn’t let you. It’s what I’m sensing. That’s what you’re saying.

You’ll have to test me.

You’re going to have to change that. Now you’re vegan?



Not strictly. That’s my aspiration.

I know you’ve talked about the pescatarian being quite a good diet.

GRS Sinclair | David Sinclair

David Sinclair – What is going to be helpful is to reserve some time within a month or preferably within the week to do what I do. That gives your body a chance to rest and recycle and put your body in that state of not abundance but adversity.

I base my comments on actual numbers. I can tell you the hazard ratio, which is a way of predicting your chance of death late in life, what those numbers are. I looked them up and it’s clear that if you’re on a regular Western diet, let’s call that one, that’s the level, and then zero would be you’re immortal. With a pescatarian diet, it’s 92%. The lower, the better. If you go vegan, it’s 88%.

It’s because they’re having less fun. That’s why they’re not as high. How do you navigate fasting with this vegan diet? I know there are a couple of weeks where it’s uncomfortable. For anyone reading, if you think that you’re going to achieve all of these things like looking great, losing weight, and all these things without a little bit of discomfort certainly in the first few weeks, that’s not realistic.

There are hacks that make it easier and I’m all for making stuff easier. I’ve skipped breakfast for most of my life just so I’m not hungry. If I eat breakfast as well as lunch and dinner, I would be heavy. I’d be obese if I did that.

How do you know that?

Because I used to be obese.

Was it eating the wrong things or it doesn’t suit you to eat often?

I’m metabolically efficient. If I eat something like pasta, the next morning I can feel that I’ve gained weight overnight. We were metabolically thrifty in my family, my father, grandmother. We tend to put on weight easily. As a kid, my mother, like a lot of mothers especially in the 1970s, would say, “Three meals a day, feed, feed, feed.” That’s how they showed love. That was my mother’s way. I would be given breakfast, lunch, and dinner, and I ended up carrying a lot of weight. It was embarrassing to suddenly change the way I thought about nutrition.

The moment that I had any governance over what I ate when I left the house and went to college, I cut out breakfast. I started eating carrots for a couple of months and shed fifteen kilos, whatever that is in pounds, which is a decent amount. I got down to a set point that I had up until not too long ago, which I couldn’t break through, by the way. I still had some love handles. You saw me when I showed up first at your place a couple of years ago.

You’re more compact and more lean than the last time I saw you.

I haven’t had a body like this since I was 20 because of the diet changes and skipping meals. What I do now is I try not to eat until late afternoon. The hack for that is for the first few weeks, fill your body with liquids, no sugar, just water or tea. Coffee is fine. You fill up. If you need a snack, some nuts, a bit of dark chocolate over 80% cacao.

Which nobody wants to eat, by the way.

I love it.

You keep telling yourself that no person that loves chocolate is like, “Yeah, I love that bitter stuff.”

It’s full of polyphenols.

It’s better than not eating anything. Sometimes people think they’re hungry, but they’re just dehydrated. They say that quite often.

Or they’re bored and stressed.

That’s what I was going to ask you. You work and you have a lot of stress. You might be calm and you speak calmly, but you’re navigating a lot of things. When we are stressed or bored or tired or dehydrated, we will poke around and look for something to snack on because it’s something to do. Did you find having liquid took you through it?

Yeah, it helped but I still go to the kitchen, open up a cupboard, and be like, “I want to eat that.” Then you have to make the decision, “Do I do it or not?” I fought it most times and I would close the cupboard door and make a cup of tea or something. That was the trick. You’re right, it takes three weeks. What’s happening during that process is that your body is learning not to put out ghrelin, which is coming from your stomach, which is this sense of hunger. It’s fake. Sense of hunger isn’t real.

Your brain is going, “I need food. I’ve got low glucose.” After three weeks, your body stops doing that. Instead, your liver wakes up. Your liver can make its own sugar called gluconeogenesis. I know this for myself because I occasionally wear one of these monitors. Levels Health is the one that I’ve been using, but there are a bunch. You can see the effects of fasting on your blood sugar levels.

You can get familiarized with what foods impact your glucose levels by wearing a monitor like that. For example, you say, “White rice is not so good for you, but potatoes are fine for you.” The only reason you know that about yourself is because you’re checking. I’m a person who believes in feeling. I’ve been doing this all a long time. There’s something important about getting an education. One of my favorite foods in the whole world is popcorn. I love it. I can’t tell you how much I love popcorn. I know it kicks my ass. I could feel it almost instantly. It kicks my ass in a real way. I even think my heart rate goes up. It is not good.

Do you put butter on it, too?

For any popcorn, why bother? That’s 80% dark chocolate. If I’m doing something, I’m going to do it. There’s something great about understanding how your body works, like, “I can get away with this.” Some people can eat the same things. One person’s glucose level goes up, one other person does not so much. I encourage people if they’re going to take this on, a feeling will be good once you understand how you respond to things. In the beginning, to measure it is great because you can have a friend or somebody next to you and it doesn’t impact them at all and for you, it’s not going to work.

We have different microbiomes as well or different bacteria that will digest popcorn differently. You can change your microbiome.

Let’s talk about that. Do you actively figure out ways to make sure that that’s balanced? How’s that working? It’s such a huge part of the whole health picture.

I don’t actively change my microbiome, but I know it’s changing in response to what I eat. I know that from science, but I can tell that in myself because when I switch my diet from something to something, for the first week, it’s hell going all the way down. My body wants to reject it. Particularly if I go back to a high-fat Western diet from being clean and lean, it’s hard. My stomach doesn’t have enough acid to break down the meat, and then it gets into my intestine and the bacteria are like, “What is this stuff? We don’t like this stuff.” I get indigestion and then out the other end, it’s a mess, too.

You’re not eating raw. You’re eating most things cooked. Salad is raw, but sometimes raw is tough on you in a different way. It can be tough on people.

I like to snack on raw stuff. Snap peas are a great one. Peppers, I do fine with those.

You’re like a new person. You’re talking about snacking on peppers and it’s amazing.

If you skip breakfast and lunch, I’m enjoying food a lot more than I used to. I don’t take food for granted anymore. Like you said, that breadbasket, you shove it in and you don’t even enjoy it. Now, I love food more than I ever have and it has improved my life. It’s not a sacrifice. I don’t feel that way at all. You need those few weeks, especially with the fasting, so I try to only eat dinner.

If you’re not going to a social dinner, which you probably go to quite a few, I would imagine, what time do you eat? You must eat early.

No. I probably would have a little bit of nuts around 3:00 or 4:00.

Do you have a favorite one?

I have a whole cupboard full of nuts.

Are you an almond guy or a cashew guy?

I love cashews.

Do you eat mac nuts? Those are good.

Yeah, I do. I’m Australian so there’s a lot of mac nuts. Not so much because a lot of them have a lot of calories. I do have them and enjoy them, but I tend to also do Brazil nuts, which I don’t like.

I don’t like them either. People go, “Just one.” I go, “They’re disgusting and weird.” People love them. When people do, “Brazil nuts,” I’m like, “No, they’re not good.”

Walnut is still a favorite.

Yogurt in the morning with your supplements, maybe some matcha, water all day long, maybe some coffee. That doesn’t impact your sleep, does it?

I stop drinking caffeinated beverages around 1:00 or 2:00. I don’t go beyond that.

If you need a snack, it’s something raw. Maybe a baby’s handful of nuts, not Shaquille O’Neal’s handful of nuts.

Just a few to nibble on and to get through the day. I might have a little piece of dark chocolate.

Then dinner is 8:00?

[bctt tweet=”There is some satisfaction that you have control over your body. A lot of people, myself included, thought we’d never get rid of these love handles and they’re gone.”]

It depends. It’s usually later. At home, it’s often 8:00, 9:00. When I eat out, it’s 7:00, 8:00.

Food is such a social thing. It is such a part of our lives. I know that your energy is good, your cognitive function is good, you look incredible. Has that been enough of a reward for some of the things that we change? Has that given you enough of a win that you’re like, “It’s well worth it.”

Are you kidding? To have your brain back? For sure.

“Do you like to have this body, Gabby?” I’m being serious.

It does feel good to be back to what I looked like when I was 20. I’m not a bodybuilder and I’m not a model, but there is some satisfaction that you do have control over your body. A lot of people, myself included, thought I’d never get rid of those love handles. It just wasn’t in me and they’re gone. That’s cool. I finally did it. It took me a couple of decades to get there and I learned how to do it. It took a change in what I eat and when I eat.

I want to encourage people that it’s important to make changes so that we exercise and flex that discipline. I do that myself. I see that the reins got a little loose on some things and I’ll try to pull back. For anyone reading, it’s 2 and 3 weeks of less fun, let’s face it. Once you get into the habit, the other great thing is that we could give you the donut but it wouldn’t be as good, it wouldn’t taste as good, it wouldn’t feel good, it wouldn’t be worth it anymore. You have to believe that that’s on the other side of it.

The question I have is if somebody is more of a performance athlete or their wattage is big, you do a lot of head-brain fatiguing athletics, but there are people who maybe are banging a lot of iron or they’re doing triathlons for fun, whatever that is, can you sustain this? What would you change for those types of people?

This is one of the conundrums. To bulk up, the body prefers a lot of protein. There are a fair amount of carnivores, meat-eaters. People take a lot of protein and protein shakes because the body does put on more muscle, but not by a lot. If you look at Game Changers, it’s a good documentary that shows that you need to eat a lot more plants to get the same amount of protein. Plants are made of protein. What do you think they’re made of?

It would be the fasting part. Do you think that in a way, maybe once a month or once a week, they can go these longer periods of time, but they might need more calories?

No doubt. The way I would science it based on everything that I’ve read is, by all means, you can build up muscle, you can run. That’s what you want to do. Supply your body with the nutrients to do that and the calories, of course. You don’t want to be a calorie-deficit. We’re not talking about malnutrition or starvation. We’re talking about maintenance of body weight, at least. What is going to be helpful is to reserve some time within a month or preferably within the week to do what I do. That gives your body a chance to rest and recycle and put your body in that state of not abundance, but adversity. That adversity mimicry is what gives you longevity.

What I’ve learned from studying these mice for years is if we put them on a molecule or a treadmill or some other intervention consistently, here’s the thing that blows my mind, it doesn’t work as well as if we give it every other day. We pulse it. You do need a rest period. There are occasions when I don’t take my supplements and I’m not worried about that.

Let’s not talk about athletics. Do you find that there’s a harmonious or an appropriate formula for the amount of recovery? A lot of times, hard-charging people forget the importance of recovery and time off.

I coach some people as well and look at their biomarkers. I can tell when they’re over-exercising. That’s easy. Cortisol levels will go up. Creatine kinase is up. Back off in the exercise because it’s putting too much stress on the body and you need that recovery period. You do not want cortisol levels chronically high. That’s the severe stress, over stress. A little bit of stress is good. It doesn’t kill you. It makes you stronger. That’s what I’m doing. If you overdo it, you go the other direction.

When you and Huberman talk about this from the two sides, what does that look like? I’d love to know that. I came from a generation where it was like, “Bang iron. More.” You’ll see a group of men where it’s this idea of like, “This is how I’m going to stay young.” The problem is it perpetuates an idea that for other people, if you’re not doing that, you’re not going to be young, fit, and have this vitality. There’s maybe a place in between for the long run.

Look at the ancient Greeks, that to me is an ideal. Not just the look but physiologically, having some muscle mass. You’re not a total wimp, wasted away. You need muscle. If you’re on testosterone, you need muscle among other things. You don’t want to fall over and break a bone when you get older. The Greeks weren’t massively built. They were lean, fit, and slightly muscular. That to me is longevity right there.

You can hear a group of men that are like, “What are you? Crazy?” We do talk about it in our house. Laird goes about things naturally. He will restrict his eating. With that, he’s naturally a good size person but it’s not a weird amount of leanness.

He’s like a Greek god.

In his world, he looks like a high-performance athlete but there are super freaks. Sometimes that has bled into our psyche like, “That’s the picture of health.” What I’m reminded of are that tightness and non-watery muscles. Things like that are not an indication of health.

Not long-term health.

It’s the price on the other side. I’m bringing that up because we’re talking about long-term health, longevity, and vitality. You will look older later if you’ve done some of these things to keep all this mass and to do all these things. It’s hard on your joints. A myriad of things are different. Can we talk about what you have been finding? I’m fascinated about this. How’s your eyesight? Can you read a label at a grocery store? Have you gone to the grocery store?

Yes, I can read fine without any glasses.

It’s some weird joke that they’re playing on people. Especially when you’re trying to figure out what’s in the bag and you’re like, “I don’t know what the hell’s in there so I’m not even going to buy it.” It is super small, even if you’re 15. I’m now at a place where I can’t even go doing this. You are seeing improvement in vision.

Do you mean in the mice or myself?

Both. Whatever you can freely talk about. Let’s stick to the mice since that’s where the science is.

I’ve been measuring my eyesight as well at a doctor’s office. My eyesight has been getting better over 2021, so it’s possible to reverse that aspect of aging. I can see well now long-distance and up-close, but it was worse a few years ago.

Is that inflammation? What’s happening that you are able to impact that?

It’s unclear how it’s possible for that to happen. What causes the problem with old age is your lens gets stiffer and your muscles have to work harder to focus. They get tired. You can have your lens replaced now. That’s a bit extreme, but you can do that. It’s out there. It’s cutting-edge medicine. If I had bad eyesight and I was old, I would do that. It also gets rid of cataracts.

GRS Sinclair | David Sinclair

David Sinclair – People take a lot of protein because the body does put on more muscle, but not by a lot. You need to eat a lot more plants to get the same amount of protein. Plants are made of protein.

You’re too young for that. Of course, if I’m 80, all bets are off. If they have surgery for that, let’s do it, especially if you’re doing a lot of the right things. That’s how I feel about this. I feel like everything that you can control and do a good job of, do that. If there are things happening and they’ve got something out there for it, why not?

I prefer to preserve what we have rather than replace it. Usually, the replacement is not as good. Getting to the eye, what we discovered in mice was we could cure blindness in mice by making their eyes much younger. What we think is we understood a major cause of aging and we can now drive aging forwards in mice easily. We can now drive it backwards as well.

You put them on social media for a couple of weeks.

Put the mice on TikTok.

I’m serious. That stuff will kill you.

That drives you forward. I thought that would make you a baby.

That makes you old.


That’s the screen time, your posture. Everything is not good. I know that you cannot give suggestions on what vitamins to take, but if you could dictate to yourself, “These are the things I’m going to do.” We know fasting, moving towards colorful vegetables.

You don’t have to be a vegetarian, but become more plant-focused. That’s how I would describe it. Eventually, you won’t want to have as much meat.

I learned an interesting thing interviewing Simon Hill because a lot of people will be like, “I cannot eat beans. The microbiome is killing me.” He said, “You’ve got to work up to some of these things.” I want to remind people if they’re trying to do this, it’s not an overnight thing. You’ve got to work into it, see how you feel, and things like that. That’s important. If someone was like, “I’m going to explore supplementation as support,” I want to bucket this for people as we start to wrap up.

My mainstay is the NMN to raise the NAD molecule to turn on defenses. There’s the resveratrol that also helps with that from red wine as a supplement in my yogurt. Quercetin or fisetin are relatives of that molecule, another couple of polyphenols that not just rev up metabolism and work like resveratrol but also kill off old cells. That’s both useful.

There’s the metformin. There’s a question about whether you should take metformin every day because it does inhibit your ability slightly to build up muscle bulk. In an abundance of caution, I don’t take metformin on days I work out. It’s easy. I’m not working out every day like some people, so that is easy for me. Look at the data if you can. Metformin doesn’t dramatically reduce your ability to build muscle. It’s a 5% difference and you can make that up by doing a few more reps.

What is the thing I was reading? People are taking almost a 2 to 5 times recommendation for sleep. I have to try to remember that. I wanted to ask you about that. Are you interested? Do you like this idea of the AKG and the spermidine? How do you feel about that? You’re still experimenting and you’re not going to say anything about that yet.

I like the idea of being healthy and younger, but I have to see it point in the right direction. The jury is still out because it’s fairly new in my body, and we’ll see. So far, the numbers are headed in the right direction.

What about sleep? How much sleep do you get?

Do you want to know the truth? Because that’s my advice. That’s one thing that I preach, but I don’t practice.

It’s not about you being perfect. I’m just curious. We all know 7, 8 hours, that’d be great. Nine could be great for certain people. What are you able to get done based on your lifestyle, your personality, your schedule?

A good day is 6, a bad day is 2.

Is it that you can’t sleep or you’re just working and you don’t go to sleep?

I’m working. I have stuff to do. I have to catch up on things. I’ve got friends and family in Australia and they’ll call. It’s all of that. Usually, it takes a while for me to fall asleep so I read a book or do something like that, read parts of a book. I travel a lot, so I’m on planes and whatever, so that’s a problem. Although NMN does control the body’s circadian rhythms, the sleep-wake cycle. I use NMN to give me a boost when I land in a different time zone.

I don’t know if it’s true or not. Laird was experimenting with fasting on days he’s flying because then you reset easier and jet lag seems to be less impactful.

There’s science behind that. That’s for real. What drives your body crazy and why you feel sick when you land is your brain will reset because it’s got sunlight, but your liver is now on a different clock. It thinks it’s nighttime when it’s daytime and then your body feels like crap. You can reset the parts of your body. In mice, it works. Raise those energy levels back up when they’re supposed to be high, which is in the morning when you wake up. That’s why I take my NMN in the morning to give myself a full reset. What Laird is doing makes a lot of sense.

Laird will fly to Portugal from Los Angeles and not touch any. He won’t eat. Breakfast with yogurt for the supplements because you need the fat or the fat maximizes the opportunity, because it’s not sugary, is that part of the benefit? I know it’s only a little bit. When we’re directing people, it’s like, “This isn’t a huge bowl of strawberry yogurt with honey on it.” Just to remind people.

That’s important. Definitely anything sweet from sucrose, which is cane sugar, beet sugar, I don’t even touch. I don’t go near that, especially for breakfast. It tastes terrible to me at this point. It’s usually plain Greek yogurt or plain coconut-based yogurt, and it’s not a lot. I have a little cup and I put maybe two teaspoons in there and that’s enough to mix it in. It looks disgusting though. Once you’ve got those oranges, whatever molecule is in there, resveratrol is like cement, it’s not a good look.

Look in the mirror, then you’re okay. You’re like, “It’s working.”

One of the things that convinced me was vanity. Serena said, “You won’t just feel better. Trust me, you’ll look better,” and I went, “Now I’m doing this.” She’s right.

I’m telling you, I feel and I know that you’re tired. I can tell that you’re tired not because you look tired. I can just tell and I’m like, “He looks amazing.” Whatever you’re doing is working 100%. I told my friend Elijah that we would get into stevia because Laird has this argument that anything that bangs the back of your throat that’s sweet, there’s no way you’re not having a physiological response. Elijah’s like, “There’s no data showing.” I have to listen to this dialogue for a few years. From what you know, where does stevia and how to take it?

I’ve looked at all the research on sucralose. This is in the yellow packets if you’re wondering which one it is. There’s a lot of research in rats and some in people that show that if you simulate sweetness on your tongue, your brain starts to freak out and identify that there’s actual blood sugar in your body even if there isn’t. There’s a double whammy, which is that these molecules are modified by the microbiome and that’s bad, too.

[bctt tweet=”If you just base it on how you feel, that’s not good enough. You have to look at the numbers.”]

I’ve been weaning myself off Splenda, sorry for the makers of Splenda, but this is the science. I went on to stevia. You also have educated me that taking stevia does the same thing. It’s tricking the brain into thinking that it’s sweet and the meal that you’re eating at the same time is full of sugar. The next time you eat stevia, it’s going to react the same way. You’re training your brain like Pavlov’s dog. The advice that I’ve heard is if you have stevia, do it when you’re having liquids that aren’t full of sugar so you don’t train your brain to respond that way and it’s better overall for your body.

Sometimes when you crave something sweet, it’s maybe not as punishing. We want to avoid sugar. I did appreciate one thing that you talked about on your Lifespan podcast, “If you are going to have dessert, have it after you eat. Don’t eat that first.” I do appreciate that you’re not saying, “Never have dessert but if you are, have it after a meal. Don’t start with that.” Let’s say someone’s eating other food like carbohydrates, do we know if it’s better to have a salad at the top or the bottom of that?

The best hack is a little bit of protein and then have the carbs. It does seem to lower that spike and get your body ready for what’s coming. That works for me well.

Are you having fun doing the podcast and stuff? Is it nerve-wracking because it’s new? You did the book so you had to already consolidate information, break it down, and communicate it so people like me could understand it. Is there something about you where you’re like, “This is such an unexpected thing in my life I’m doing as an extension of my career.”

It’s wonderful because my whole life, I’ve been an educator. I like speaking to people. I like educating them and they go away with knowledge. This is how I get my pleasure. I’m serving people with education. That’s my whole life. For most of my career with old media, it was extremely painful. Speaking to reporters who had an agenda, who wrote headlines that often their editor wrote instead, was embarrassing. I was always fearful of speaking to reporters. I was in the news a fair amount. It was not one report in a newspaper or online that was accurate. Beware, don’t believe what you read even in newspapers. Typically, it’s bad.

This ability to reach people the way I’ve always dreamed of is a dream come true for me and I love it. I’m not going to give up my love at Harvard because of the work that we’re doing reversing aging during blindness, etc. People would be upset and I’d lose my motivation. When I go to the lab, I’m invigorated like Willy Wonka in his chocolate factory. This is what I do. I’m staying at Harvard, but I’m increasingly becoming a global educator through written word and spoken word.

You’re talking all about health and every show is about health. That’s a lot of ideas. I can pivot. I can talk about relationships, I can talk about anxiety, I can talk to you about science, I can move all over the place. Have you thought about that?

No. It’s never-ending. Health is a big enough topic, but I can talk about a lot of things. I’ve got companies that detect viruses. I’ve got military stuff going on that’s interesting. I’ve got companies that look at the ultrastructure of the cells that allow researchers to do crazy things. There’s a big world that I haven’t revealed to most people yet and that will come, but even within the health space, we’ve touched the surface. I bet you, there are a lot of people saying, “I wish they would talk more about this or that.” That’s why I have the podcast because I can dive in deep and give the citations and the scientific studies to back it up as well.

We talked about the AKG being something that you learned about after Lifespan. Is there anything monumental that I forgot since Lifespan, the book, that feels important to you?

There are a number of things. My lab always surprises me. When I go in, I say, “Tell me, how’s it going?” They go, “We’ve just discovered this.” It’s such a great privilege to be a professor at Harvard with these smart kids. I’ve got about 20 of them. In any one week, they’ll make some breakthrough. I go into my lab and on a typical day, which is described at the end of Lifespan, I want people to know what it’s like to come to my lab. It’s cool. By the way, I’ve got an invitation.

Don’t invite me because I’ll come.

Please do. Come and see the mice where we age them and bring them back.

I’d like you to do that to me. It’s like, “Bring it back. Don’t age me.”

I don’t think Harvard would let me inject you with our age reversal genes yet.

I’m down. Why not? I’m ready.

We could do it, but we’d get in trouble.

It’s okay.

The thing that has been exciting is that we’re looking for ways to reverse age with molecules like alpha-ketoglutarate, but there are other ones that we’re looking for. Instead of it being a gene therapy, which is how now we reverse aging in mice, hopefully and eventually people in the next few years, we’ll try it, take a pill. This is the dream of the pharaohs. We have the science. We have the knowledge. We know that there’s a backup copy of youthful information in ourselves. This is what we’ve discovered.

There are hundreds of labs working on this in 2021. Billions of dollars are being put into this. Jeff Bezos is the most prominent one, but there are a lot of people into this. It’s going to happen. What’s new? I’ll share it with you. I don’t think everybody knows what a senescence cell is. It’s a cell that has become so confused about its identity and a loss of self-identity is the main cause of aging. It said, “I don’t know what the heck to do. I’m going to check out.”

Instead of dividing, that cell will shut down, become quiescent or hibernate, and sit there. That’s a senescence cell. That’d be fine if it didn’t put out all these warning signals to the rest of the body, which results in inflammation, Type 2 diabetes, and a whole bunch of other diseases including cancer. These senescence cells are vicious. Even a little number of them in a mouse, you could put a dab onto the skin, they’ll accelerate aging. They’re bad news, so you can delete them.

I take fisetin, which is in what’s called a senolytic. It kills senescence cells in mice, probably in people. The breakthrough was that we found out that those zombies, right now we’re just shooting them. That’s a problem if you’re killing off important cells that you need. Brain cells become senescent. You don’t want to kill off too many brain cells. You’d rather revive them.

It wouldn’t matter in my case. In your case, it’s important.

Come on, you’re one of the smartest people I know. What’s important is we’ve discovered that you can restore the health of the senescence cells. They wake up, they’re healthy, they grow again. That’s true age reversal and that was unexpected. If you ask almost anybody in the world who knows anything, they’d say, “Senescence is terminal and all you can do is kill them.” That’s not true.

You have a fun job. I know it’s hard, but it’s cool.

It was a slog getting here, but now I’m having fun.

Before I forget, IFAN, intermittent fasting with appropriate nutrition. I want to remind people that you’re not talking about fasting, but paying attention to getting the appropriate nutrition. IFAN, if you need a reminder. All of this takes a certain amount of planning and thoughtfulness. I don’t want people to think, “I skipped lunch.” It’s like, “Try to pay attention.”

There’s another point you just reminded me of, which is that if you don’t measure things, you don’t know if you’re deficient or have an excess of something. There are plenty of my clients that have low B vitamins because they’re on these kinds of diets and don’t eat enough spinach and broccoli. There are also people who take supplements that overdo it. Vitamin B12 is through the roof, which also is bad long-term for the cardiovascular system. You cannot optimize what you don’t measure and you might be doing yourself more harm than good by taking these vitamins.

GRS Sinclair | David Sinclair

Why We Age―and Why We Don’t Have To

That’s important. That’s why I do my blood work to get a sense of it. This is the first time I’ve had my bloodwork done and I was not vitamin D deficient. I’m not kidding, COVID made me so aware of taking my vitamin D that it’s the first time that I’m like, “It’s not great, but it’s not low.” With quercetin, I talked to Dr. Perlmutter. He did the Grain Brain and things like that. He was talking about this low-level inflammation and how great quercetin is for that. Laird’s always like, “What food has quercetin?” Do you know what foods have a lot of quercetin?

It’s onions and apples, but there’s not enough.

Capers have a lot of quercetin.

You can do eight bottles of capers?

You’re vegan now.

You’ll die of salt.

Health is everything. One thing supports one. Getting your uric acid down, the quercetin helps with that and in these other areas. I try to remind people that a rising tide does lift all the boats. It’s not like, “This is just good for this one thing.” It’s good for a lot of things.

Because these molecules, these polyphenols, we call it pleiotropic, which means they have lots of activities, defenses against aging. I’m not saying, “Take this because it’s an antioxidant.” I’m saying, “Take this molecule because it will turn on your body’s defenses against aging.” You’ve got a whole bunch of proteins waiting to be turned on. You can turn them on to defend yourself by exercising, by being a little bit hungry, by being in a sauna, by being cold, which I’ve done a number of times here.

That’s all about this adversity mimicry that turns on your body’s natural defenses. We don’t know all the things they do, but we do know that they turn over proteins, defend DNA, and preserve the information that allows you to be younger for longer. That’s an important point, which is that it’s not one activity. There are hundreds of activities that you can achieve with just one molecule.

This is my final question because you navigate your life in an interesting way.

Now I’m worried.

I’m just curious. You and I both have teenagers. Have you learned something as a parent? You have three kids so you’ve learned some lessons. Have you learned something that seems to work when navigating teenagers? I’ll give you mine, for example. I learned that if I listened more than I solved, that if I didn’t worry but I believed in, that there were certain things that seem to work out better. This idea of that in which you resist persists. I used to lean in harder on my older kids when they were going through their phases.

Certainly, as I’ve gotten deeper into parenting, I’m realizing to have a little more faith and this too is part of the process. This is a phase, they’re going to be okay, all these things. I’m wondering, as a person who is bright and is in charge in certain ways of your universe because you’re dialed in person, what have you learned as a parent that showed up a skill you didn’t have when you started?

I’m not the greatest dad, I’ll admit it, and I’ve been trying to get better. I’m career-oriented and my kids suffered as a result. It’s one of those things I regret. When I was home, I was doing everything I could to teach. This is what I do. We had those giant sticky notes all over the kitchen for years with things that they could learn during dinner. That was my way.

I haven’t been a great dad. I wasn’t home a lot. I have three kids. The two older ones were born female. They’re now known as they, which was also a hard thing for me to get used to. We’re talking about a decade ago. It was new and unusual. I used to not take them as seriously as I should have. I could use an excuse that I’m just a joker and I’m Australian, but it was bad parenting not sitting down and saying, “I hear you. I understand it’s hard.” I would say, “Yeah, whatever.”

“He, she, they, that’s funny.” I made a joke about it. That was bad parenting and I regret that I did that. These days, I listen and I’m concerned about them. If they talk to me, especially as a teenage female, it’s a blessing because otherwise if you don’t listen, they’ll learn that they don’t feel safe when they talk to you about stuff.

That’s a beautiful point. Even though sometimes it’s hard to hear or it’s hard to listen, just be glad that they’re talking. It’s a beautiful thing. Dr. David Sinclair, your book is Lifespan. Your podcast is Lifespan. You have a co-host, Matthew LaPlante, who was the co-author. He creates some infrastructure and gets you set up.

I appreciate you taking on these topics and also making it achievable. I’ve listened to the shows that you have so far. Anyone who feels at all intimidated, it’s not that at all. You have a good speaking voice. It’s calming. It’s going to kick ass, you and the science mafia, Andrew Huberman. I’m excited to see what you guys do. I appreciate your work and I appreciate you a lot. Thank you.

Thank you, Gabby. The feeling’s mutual, by the way. You’re an all-around awesome human being, so keep doing what you’re doing, too.

I’ll work on it.

Thanks for having me on.

Thanks so much for reading. If you’d like, rate, subscribe, and leave us a review. All of my music was graciously done by Frank Zummo and Tom Thacker. If you want to see some of the behind-the-scenes action, follow me, @GabbyReece. Remember, don’t miss new episodes every Monday.

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About David Sinclair

GRS Sinclair | David Sinclair

David A. Sinclair, Ph.D., A.O. is a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. He is best known for his work on understanding why we age and how to slow its effects. He obtained his Ph.D. in Molecular Genetics at the University of New South Wales, Sydney in 1995. He worked as a postdoctoral researcher at M.I.T. with Dr. Leonard Guarente where he co discovered a cause of aging for yeast as well as the role of Sir2 in epigenetic changes driven by genome instability. In 1999 he was recruited to Harvard Medical School where he has been teaching aging biology and translational medicine for aging for the past 16 years. His research has been primarily focused on the sirtuins, protein-modifying enzymes that respond to changing NAD+ levels and to caloric restriction (CR) with associated interests in chromatin, energy metabolism, mitochondria, learning and memory, neurodegeneration, and cancer.