#359 Reversing Biological Aging and Extending Lifespan - Matt Kaeberlein PhD

Matt Kaeberlein (0:00)

I don't know if aging can be reversed or not, biological aging, like, as a whole. Certainly we have to say it's theoretically possible. I think those people can almost all get 15 years of quality life back. Then if you fix that, if you reverse those, maybe you can reverse everything else.

Siim Land (0:14)

Welcome to the Siim Land Podcast. I'm your host Siim Land, and our guest today is Matt Kaeberlein.

Matt is a PhD and researcher in the biology of aging. He's one of the world's most renowned names in longevity, life extension, and healthy aging. This episode is brought to you by the Biohacker Center, your home for all biohacking gadgets, longevity supplements, and functional foods. You can get everything starting with spermidine, liposomal NMN, magnesium, as well as red light therapy devices, blue light blocking glasses, and water filters. The Biohacker Center is a company I'm personally involved with and invested in. If you want to support this channel while providing yourself with the supplements and devices you are gonna get anyway, then the Biohacker Center is the best place to do so. Head over to biohackercenter.com and use the code SIIMLAND for a 10% discount.

Matt, welcome to the show.

Matt Kaeberlein (1:02)

Thanks, pleasure to be here.

Siim Land (1:03)

When you look into the internet and do some research about aging and the biology of aging, then you've been around pretty much almost since the beginning of that, at least in the modern, the past few decades of researching about the biology of aging actually, and how does it work, and what causes aging, et cetera. So yeah, I'm definitely super excited to have you on the show.

And yeah, maybe we can talk about, or we can start with what has been some of the shifts over the past few decades in terms of the aging research and have we seen any massive breakthroughs in the last few years?

Matt Kaeberlein (1:41)

Sure, yeah. So I guess maybe where I would start is to say, so you're right, I haven't been around since the beginning of aging research, but I've been around for a while.

I actually started in the field around 1998 when I was a second year graduate student at MIT. I started working with Lenny Guarente. And so maybe the way to frame the answer to your question is to start there and say, I think that was a really interesting and exciting time in the field because prior to, I would say about 1990, most of the work in the field had been fairly observational, right? People would see that certain things changed with age. Hormone levels changed with age, things like that. Functional measures changed. But we didn't really have any insight into the mechanisms. And by that, I mean genetic, biochemical, molecular. And that really all started to change, I would say, in the 1990s when people started to identify genes that affected lifespan. So I feel very fortunate to have come into the field at that time because there was a big burst in knowledge as people started to do genome-wide screens and things like that to find mutations that affected lifespan and then started to characterize how that was working from a very mechanistic level. So really, I think much of what we understand about the biology of aging today, the hallmarks of aging, for example, really derived from that work that was happening in the late 90s, early 2000s where people were starting to identify pathways and mechanisms of aging.

A couple of things I would say that I think are kind of fundamentally now accepted in the field, but which really weren't when I started. One was that there are evolutionarily conserved mechanisms of aging. In other words, the biology of aging is, you know, to a large extent similar, if not identical, across different animals. That really wasn't appreciated, I think, when I started in the field.

And then also the fact that we can, it appears that we can actually intervene in the biology of aging and have a positive impact during adulthood. Again, I think, you know, when I came into the field, there was, it was sort of the perception that you had to start any treatment to affect life, longevity, or health span. You had to start early on to get those benefits.

We now know from multiple examples, and I think rapamycin is one of the best characterized, but there are now multiple examples where you can actually start an intervention in middle age and get many, if not all of the benefits that you get from starting that intervention in young age. That's not true for everything, and we may want to get into this. I think, you know, caloric restriction is an example where it seems as though the benefits that you get, at least in laboratory animals, are much larger when you start earlier in life. But at least for some things, you can get a significant benefit. There are, you know, partial rejuvenation properties, at least functionally, from some of these things, which is super exciting. I think, you know, from a translational perspective, being able to eventually bring these into the real world to have an impact, it's much more appealing, obviously, if you have an intervention, you can start in middle age, as opposed to something that, you know, very, very young people have to take. So there have been huge advances, lots of things I didn't talk about, but to me, those are a couple of things that I think have been particularly important and, you know, in some ways have been a paradigm shift in the way we think about the biology of aging.