#482 Why Scientists Believe Lithium May Be a Longevity Molecule

Jon Berner (0:00)

We all get a different deck of cards. You know, the law of large numbers says that we're not perfectly optimized, and that in some people, an unknown dose of lithium could potentially lower your risk of Alzheimer's and aging, and possibly a higher dose of lithium could allow you to be more emotionally stable.

Siim Land (0:19)

Dr. Berner, welcome to the show.

Jon Berner (0:21)

Thank you.

Siim Land (0:23)

Yeah, I'm excited to have you on the show because you have a lot of experience with one particular compound that has become quite popular over the last few years and months, and that's the lithium. So yeah, I'm really excited to dig into the research on lithium and your experience and your practice with it. So I think people have a very interesting show ahead of them. So maybe we can start with how did you, let's say, because you've been using lithium for a lot longer than it has become popular over the last few years. So how did you, I guess, discover lithium?

Jon Berner (1:04)

Well, lithium has been used as a mainstay in psychiatry for decades and decades. And there's a fragment of the population that clearly should be on lithium in terms of a normative gain of function in the glycogen synthase kinase 3-beta pathway. And these are typically people with bipolar disorder. And you'll get arguments that are unanchored from solid epidemiology about what group of people should be on lithium and what dose. But we know about 1% of the population has bipolar 1, which is severe hospitalization, disability, suicide attempts. 3% of the population has mild form, where they occasionally miss work for weeks or months and make major financial or sexual indiscretions. And then there may be a much broader population, maybe as high as 10% of the population who have very subtle forms of mood and energy instability that would clinically benefit from lithium just in terms of their emotional stability. Well, this is a drug that has a very broad population indication in terms of mood disorder. And then when we move into the even broader distribution, which would be even at lower dosages, what percentage of the population would benefit in terms of aging and Alzheimer's prophylaxis, that hasn't been studied.

We have very good, if you will, natural experiments in terms of random variations in the water supply, which almost without exception show increased longevity, decreased rates of dementia, suicide attempts.

With even small dosages of lithium. So when you talk about lithium, it's not really a drug. I mean, the drug is irrelevant. What is much more important for you and for your patients out there, I mean, your patients, your podcast listeners, is just this concept of random assortment of three billion base pairs. And we all get a different deck of cards that is randomly distributed. And the law of large numbers says that we're not perfectly optimized. And that in some people, an unknown dose of lithium could potentially lower your risk of Alzheimer's and aging, and possibly a higher dose of lithium could allow you to be more emotionally stable in a very broadly defined way. And we don't really have yet a technology to assay that deck of cards, the 3 billion base pairs that you get from your parents, in terms of giving each individual person, what is the right dose of lithium for me? And this is a critical issue in community health. And in your own personal decision about what do I put into my body that is going to help me optimize my life span, health span over a lifetime?

Siim Land (4:50)

Hmm, yeah. Yeah, you are referring to the idea that lithium has been used for bipolar disorder for a long time, and quite not recently, but it has also been seen to be potentially useful for Alzheimer's. So there's actually one study this year that claimed that lithium deficiency was a driver of Alzheimer's disease, which makes it quite interesting for just general longevity and preventing dementia and neurodegeneration overall, beyond just bipolar disorder and similar conditions.

So what do you think is the reason for that? So first of all, why does lithium help with, let's say, mood disorders and bipolar disorder? And what are those mechanisms that could also have benefits on Alzheimer's and neurodegeneration?

Jon Berner (5:54)

Right. So biology is an engineering problem. One of the reasons I'm excited to talk to you as someone who's interested in anthropology rather than psychology is the concept that human behavior is determined by evolutionary constraints, not so much by verbal concepts and self-image and self-esteem sort of things. But we have this three-pound brain that has unbelievably difficult energy constraints on all sorts of multiple timescales. And so, when you're designing, when evolution designs the system, it has to optimize inefficiently, right? And so, you talked about, I think, you've talked about this issue between the persistent predator, you know, that's skinny and sweats easily, you know, in equatorial Africa, you know, and a different population that stores fat well in areas with lots of seasonality.