Essentials: The Biology of Slowing & Reversing Aging | Dr. David Sinclair

**Andrew Huberman** (0:00)
Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now, my conversation with Dr. David Sinclair. Thanks for being here. I have a ton of questions for you about aging longevity, lifespan, actionable protocols to increase how long we live, et cetera. I just want to start off with a very simple question. What is the difference between longevity, anti-aging, and aging as a disease? Because I associate you with the statement, aging is a disease.

**David Sinclair** (0:43)
Right. Well, so longevity is the more academic way we describe what we research. Anti-aging is kind of the same thing, but it's got a bad rap because it's been used by a whole bunch of people that don't know what they're talking about. So, I really don't like that term anti-aging. But aging is a disease and longevity are perfectly valid ways to talk about this subject. So, let's talk about aging is a disease. When I started my research, disease here at Harvard Medical School, it was considered if there's something that's wrong with you, and it's a rare thing, has to be less than 50% of the population, that's definitely a disease. And then people work their whole lives to try and cure that condition. And so, I looked up what's the definition of aging, and it says, well, it's a deterioration in health and sickness, and you can die from it, typically you do. So, I'm thinking that sounds pretty much like a disease, but the caveat is that if more than half the population gets this condition, aging, it's put in a different bucket, which is, first of all, that's outrageous, because it's just a totally arbitrary cutoff. But think about this, that we're ignoring the major cause of all these diseases.
Aging is 80 to 90% the cause of heart disease, Alzheimer's. If we didn't get old and our bodies stayed youthful, we would not get those diseases. And actually, what we're showing in my libels, if you turn the clock back in tissues, those diseases go away. So, aging is the problem, and instead, through most of the last 200 years, we've been sticking band-aids on diseases that have already occurred because of aging, and then it's too late. So, there are a couple of things. One is we want to slow aging down so we don't get those diseases, and when they do occur, don't just stick a band-aid on, reverse the age of the body, and then the diseases will go away.

**Andrew Huberman** (2:27)
That clarifies a lot for me. Thank you. Can we point to one specific general phenomenon in the body that underlies aging?

**David Sinclair** (2:35)
Fortunately, during the 2000s, we settled on eight or nine major causes of aging. These eight or nine causes, at least for the first time, allowed us to come around and talk together. We put them on a pizza so everyone got equal slices. But I think that there's one slice of the pizza that is way larger than the others. We can get to that, but that's the information in the cell that we call the epigenome.

**Andrew Huberman** (3:00)
Well, tell us a little bit more about the epigenome. Frame it for us, if you will, and then we'll get into ways that one can adjust the epigenome in positive ways.

**David Sinclair** (3:11)
Yeah. In science, what I like to do, I'm a reductionist, is to boil it down. I actually ended up boiling aging down to an equation, which is the loss of information due to entropy. It's a hard thing to overcome the second law of thermodynamics. That's fair. But this equation really represents the fact that I think aging is a loss of information in the same way that when you Xerox something a thousand times, you'll lose that information or you try to copy a cassette tape, or even if you send information across the Internet, some of it will get lost.
That's what I think is aging. And there are two types of information in the body. There is the genetic information, which is digital, A, T, C, G, the chemical letters of DNA. But there's this other part of the information in the body that's just as important. It's essential, in fact. And that's the systems that control which genes are switched on and off. In what cell, at what time, in response to what we eat, etc. And it turns out that 80% of our future longevity and health is controlled by this second part, the epigenetic information, the control systems. I liken the DNA to the music that's on a DVD or a compact disc for the younger people who used to use these things.