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Dr. David Sinclair is one of the world’s leading anti-aging specialists and currently a professor of genetics at Harvard Medical School. Just this year, he released a book called Lifespan: Why We Age ? and Why We Don’t Have To. His book talks about his work on slowing, or even reversing, the effects of aging and if we can live a healthy 100+ years. Dr. Sinclair has been named by Time as “one of the 100 most influential people in the world” and top 50 most influential people in healthcare. In this podcast interview, Dr. Sinclair talks about his motivations for studying aging and how as a kid, he learned the hard truth about being human and dying. He also talks about his current work and experiments on mice, where he was able to restore its vision and help it become young again. He also talks about his book and his cheatsheet on liver longer and healthier.
Listen to the interview here:
BioHacker: Thanks a lot for joining me, David. Appreciate it. I was actually just in Australia like four weeks ago. And you’re from Sydney, right?
Dr. David Sinclair: A long time ago. Yeah.
BioHacker: Nice. Nice. While I was there I visited Sydney Harbor and then the Willow Willow Malu. My grandfather was stationed there in World War II. So he told me about that. Like when I was in a senior center in Ohio.
Dr. David Sinclair: I’m sure the Australian girls were falling all over him with an American accent. That’s what used to happen.
BioHacker: Really? Actually, there was the Australian girl he almost fell for, but he ended up going back to Ohio and married my grandmother. So luckily, I’m alive. And then I also went to the Great Barrier Reefs in Cairns and went swimming with the fish and everything. I was a little bit actually scared of dying because I went scuba diving and I had never been scuba diving before. And I was 10 metres underwater. And I was scared. Like, I don’t know if you ever been scuba diving.
Dr. David Sinclair: I used to do it a lot, yeah.
BioHacker: There was water in my mask and I was worried about breathing it and then choking. So I was very glad I get above the surface.
Dr. David Sinclair: There’s plenty of ways to die horribly in Australia. That’s just one of many.
BioHacker: And then another thing that’s on my bucket list, I visited the rainforest and an Aborigine took me hunting of crabs with spears. I could show you photos later.
But yeah. Getting to you, though. So you’re you’re an aging specialist, and in your book you talked about your your grandmother Vera having a “seize-the-day” mindset like fight for your youth. She escaped the Soviets, anticommunism. And could you tell me more about your motivation for studying aging?
Dr. David Sinclair: Well, I’m pretty average. When I was four years old, like everyone else, I found out the hard truth about being human and that everything dies, and dies typically not very pleasantly. And the reason that I’m separated from most people is I didn’t bury that deep in my subconscious. That’s what most people do. Whereas I just kept thinking, why aren’t we talking about this more? This sounds terrible. The more I looked into it, the more I realized aging was at the root cause of all, not all, but essentially all of the major diseases in the world.
BioHacker: Now you have kind of a growth mindset and a sense that you don’t you don’t think death is inevitable. Instead, you have an engineering mindset like it’s a problem you can break down and try to solve.
Dr. David Sinclair: We can fix everything. As humans, there’s nothing we can’t do. I have great faith in humanity and ingenuity. It’s all about having a will and having the resources to do it. And aging isn’t gonna be any more difficult than flying or other things we’ve done going to the moon. In fact, ageing is turning out to be relatively simple. And given the the few resources we’ve had over the last 30 years to work on this problem, it’s amazing how far my colleagues and I have come.
BioHacker: Yes. In your presentation, you talked about this “demented pianist effect” where the DNA is being expressed in odd ways and it’s causing malfunction sort of aging-type effects. Do you see that as the central cause of aging in some ways?
Dr. David Sinclair: Yeah. My thinking has evolved like all scientists. We used to think that aging was just caused by about eight different things going wrong. And we still believed in those hallmarks of aging, as we call them. But the more I’ve studied yeast and then now mice and and increasingly humans and my colleagues have also worked on this. It’s not just me. I’ve come to the conclusion that the most likely reason we age the major driver of all of the bad stuff that happens is a loss of information, not at the genetic level, which would be the piano, but at the epigenetic level, which is the piano player.
BioHacker: Yeah. And do you see, like Claude Shannon’s theory is as sort of at the heart of how to solve that in a way.
Dr. David Sinclair: Yeah. Well so Claude Shannon was brilliant. He realized that you could actually transmit information over time and space accurately. Hundred percent. So long as you had a backup copy. And using that, we’ve searched for the backup copy of youthfulness and a way to restore the piano player to being pristine. And I think we found it.
BioHacker: Is that what the process was? You described in your talk about the mouse that had that pinched nerve and you were able to sort of restore it by giving it antibiotics? I didn’t actually understand the mechanisms of how that worked.
Dr. David Sinclair: Yeah. So it’s a gene therapy that turns on three Yamanaka genes in the eye. So we deliver the genes, then we give antibiotics. The antibiotics turns on the genes and then they they get their vision back in the cells at the back of the eye, become young again. We can measure their age and they literally are young. You can’t tell a difference. And so now you get old mice that can see again.
BioHacker: And it’s sort of like a targeting of the expression of genes that restore it.
Dr. David Sinclair: Well, the three genes that we put in our transcription factors that turn on a cascade of repair systems, but exactly how they work, we don’t know yet. We think that it involves chemicals called methyls that are on the DNA and enzymes that remove them, because if we get rid of those enzymes, you don’t get vision restoration anymore and nerves don’t grow back. So we haven’t some idea what’s behind the clock, but not all of the inner workings. And that’s what we’re looking for, whereas that backup hard drive of our youthfulness?
BioHacker: Right. Exactly. So it’s like in Claude Shannon, there’s sort of a master information source that has the original information. And it’s like tapping back into that.
Dr. David Sinclair: Right. But where is that stored? We don’t know. Is it on the DNA? Is that a protein that binds to the DNA? Is it a quantum effect? At some other level, we’re not thinking. We don’t know. But we know that it is possible to restore the youth of cells and turn back that clock.
BioHacker: I used to think of aging as sort of the telomeres, like the base pairs sort of getting lopped off every time it divides. The Leonard Hayflick effect. Do you have a more sophisticated view of aging now?
Dr. David Sinclair: Well, Sir Leonard’s an old friend and Liz Blackburn, who won the Nobel Prize for that discovery. So telomeres are one of those hallmarks of aging I mentioned earlier. And so those are still important. I’m not saying that they aren’t, but the erosion of telomeres and the changes in gene expression patterns over time are part of this encompassing theory, which I call the information theory of aging. And the proteins that protect telomeres are also involved in this gene regulation pianist. And so as the pianist gets worse, she starts to play the wrong notes, she is also neglecting the telomeres and they shorten that. That’s what we think is going on. But all these other things go wrong as well. The mitochondria become dysfunctional, we get senescent cells as cells lose their identity or the piano player becomes too defective. And we think this is true in part because we can disturb the epigenome in a mouse by cutting the chromosomes and causing the epigenome to unravel. And we get an old mouse as a result, 50 percent older, not just looking older, but its clock is 50 percent older. We measure it. And so now we think we know one of the drivers of aging and even how to reset the cell with those Yamanaka genes.
BioHacker: Have you done a test on yourself to measure your biological age?
Dr. David Sinclair: Well, I haven’t done the actual biological methylation clock. I’d want to. It’s not easy to do. And I’m fairly busy working on the mouse experiments, but I’m going to do it. Steven Horvath, who is one of the inventors of this clock, has said that we’ll do it together. But I’m interested in seeing how I’m doing. I’m not afraid of the data. And if I’m older than I should be, then I’ll just work harder at trying to slow it down. And we know the clock can be slowed down. 80% of our epigenetic effects are actually 80% of our lifespan is epigenetic and only 20% is genetic. So there’s a lot you can do seemingly to slow that clock down.
BioHacker: My doctor is Dr. Terry Grossman. I don’t know if you ever heard of him. He wrote a book with Ray Kurzweil, “Fantastic Voyage: Live Long Enough to Live Forever”. He personally does a stem cell therapy where somehow he gets cord blood from infants and then sort of gets it injected to himself. And somehow that kills sort of senescent cells. Do you think that’s like a promising avenue to maintain youth?
Dr. David Sinclair: Ah yes. I don’t know about those particular experiments, but I think that that stem cells, if you can get them to find their home in the tissue or at least secrete factors like those tiny particles we call exosomes, they may actually be beneficial for that reason. So there’s lots of things going on. There’s complementary approaches. So we work on small molecules that boost the body’s defenses against deterioration like NAD+. Turns on the two enzymes that we’ve worked on mimics exercise and diet, healthy diet. I’m still a big proponent of, well not proponent, but I still take resveratrol. And our research still points to that being important. And metformin I take, because the 100,000 people who have taken metformin, it’s been studied, are living longer and healthier than others.
BioHacker: Cause it reduces blood glucose.
Dr. David Sinclair: Well, it does reduce blood glucose, but we don’t know why it protects against heart disease and Alzheimer’s and frailty and cancer as well. So that needs to be figured out. But the fact that it works is pretty clear when you look at the overwhelming epidemiological data.
BioHacker: What would be like the top two or three things you do practically to live longer and be healthier that might be useful for other people?
Dr. David Sinclair: Well, I wrote down everything I do in a book that I recently put out called Lifespan, and it’s on page 304 if people want to jump to the cheat sheet. The top three that having measured myself over the last 15 years that I think are doing the most is resveratrol, […], and the metformin. So I can see changes in my body, inflammation, glucose change positively when when I combine those three.
But this is not a clinical trial. Any of my colleagues who are listening might be rolling their eyes. He goes Sinclair again. But I know it’s not a clinical trial. Clinical trials will take 20 years to be proven of combination therapies. And none of us, certainly not my colleagues of my age have enough time to wait. They’ll all be in the ground by the time we figure this out fully. And I’m not going to publish my own data, but I think that it’s helpful to be able to have a glimpse into what might be real and then test it rigorously as we do in clinical trials.
BioHacker: Do you have your own personal vitamin supplements stack? Like I remember when I was in eighth grade, I did a report on Linus Pauling and vitamin C and it really got me into it, taking large doses of vitamin C to fight the common cold. Do you take like C, A, B, all those things?
Dr. David Sinclair: I don’t go crazy on vitamins. I do think vitamin D2 and K2 are the most important. I make sure I get enough of those, especially living in Boston. Vitamin D is essential. K2 will seemingly keep the calcium out of the arteries and put it back into bones, which is also something I’d like to do. But other than that, I don’t go crazy on vitamins.
BioHacker: And what do you do to help other people that you love? Like your father, like stay, stay healthier, live longer?
Dr. David Sinclair: I didn’t really do anything they asked me to do to help, but my brother got really upset that he was looking older than me. And so he said, stop using me as the negative control in the family, which wasn’t really true, but the thought had crossed my mind. But my father is a scientist, actually. We’re scientists in my family, my wife, my brother, my dad, my mother. And my father has decided to start doing what I’m doing. It’s his own life. I’m not going to stop him. And he’s doing well at 80. No, no, any no symptoms of old age. He’s still running around like he was 30 or 40.
BioHacker: And do you look back at your mom, Diana, and kind of wish you could have done something to help her? I remember her lungs filled with fluid.
Dr. David Sinclair: Yeah. Well, she got she was she contracted lung cancer when she was in her actually exactly the same age I am right now, 50. She’s at the opposite end of the spectrum. Whereas my dad wants to live healthy for longer. She didn’t care about it. She didn’t care about herself. She smoked. She didn’t watch what she ate and paid the consequences. It was real shame. And throughout my childhood, I was fighting to try and get her to take care of herself. And she did just refused to. And it was pretty painful as a young kid. Twelve year old all the way up to 20s saying when you get sick, I’m not going to come and see you in hospital. Of course, when she got cancer, I was the first person there in hospital. But, you know, you get the idea there was nothing I could do. And there are people who don’t care about their longevity. Tell you what, when she when she had one lung taken out. She cared pretty, pretty fast about that and stopped smoking. But it was too late.
BioHacker: Yeah. Thank you so much, David. Thanks for your time. I appreciate it.
Dr. David Sinclair: You’re welcome.