#390 The Key Determinant of Longevity and Lifespan - Dr Edward Calabrese

Edward Calabrese (0:00)

The biomedical world actually has missed this. And you see this right from bacteria, right up to humans and everything in between, all cell types.

Siim Land (0:09)

The ones that did develop this mechanism or they evolved these kinds of adaptations to various stressors, those are one of the ones that survived. Welcome to the Siim Land Podcast. I'm your host Siim Land. Today, our guest is Dr. Edward Calabrese. He's a toxicologist and a professor at the University of Massachusetts Amherst. Edward is one of the world's leading experts in hormesis, the concept of a dose response to a toxin or stressor that yields a positive adaptation. He's published dozens of papers and articles on the topic and has researched this for decades. In this episode, we're going to talk about the fundamental role of hormesis in longevity, biological resilience, aging, and what to do to become stronger and healthier as an individual.

Edward, welcome to the show.

Edward Calabrese (0:53)

Thank you very much. Happy to be here.

Siim Land (0:56)

Yes, I'm also very excited to have you because I actually wanted to do a podcast with you for several years, or at least I've known about your research for several years when I was learning about the concept of hormesis multiple years ago and then doing that process, stumbling upon these different studies and papers that were mostly written by you.

So you've been like one of the pioneers in this field of stress adaptation and hormesis. So I'm really excited to have you on the show.

Edward Calabrese (1:32)

No, thanks very much. I'm glad you got me before I died.

Good timing, right? Good timing.

Siim Land (1:41)

But for the people who aren't aware of the idea behind hormesis, we can start off with what is this concept and why is it so important overall?

Edward Calabrese (1:56)

Well, actually, it's a pretty fundamental question. What is hormesis? And I think the audience should know that the definition that I give is hormesis by calabrese. I mean, there are different ways to look at this, and I'll try to explain how people might see the concept of hormesis and how it plays out. And I have a very broad conceptual perspective on it.

And I think it relates a lot to how I entered this field of biology, and it really is different than most others who came on to it more recently. And that is that I see hormesis as a biphasic dose-response relationship. It's a low-dose stimulation and a high-dose inhibition. However, it's not just any type of biphasic dose response.

As I came to learn, the hormetic stimulation and dose response in general has very specific quantitative features to it. And something that I didn't know when I first started, and I didn't know this for maybe a decade or so, as I collected more and more information, and that is that I thought that the low dose stimulation could be, oh, gee, maybe threefold, fivefold, tenfold higher than the comparison control group. And when I set up my first database on this, I allowed for about a 400% increase stimulation, actually.

But as I collected thousands and thousands of examples of what I thought were these paramedic biphasic dose responses, I found that in fact that the maximum stimulation was, in general, quite modest.

It really surprised me. It really didn't come anywhere near this fourfold or 400% increase. In fact, it was very uncommon for it to exceed twofold. With the maximum mostly occurring, and this is the maximum mostly occurring, only 30 to 60% greater than the control group. And that's really a very modest increase. And this has huge implications for all sorts of biological applications. And so I began to take a look at Hormesis as simply a biphasic dose response, ultimately having a certain quantitative features. And then the next issue for me was, well, most people were saying, well, is Hormesis a beneficial response? Is it always beneficial? And as I looked more into it, I could find, yes, most of the circumstances seem to be positive or beneficial, but I found different circumstances where, at least from a human perspective, that there could be a variety of these hormetic-like biphasic dose responses where that stimulation was, you might say, undesirable, could be harmful, that sort of thing. And so in 2002, I wrote this paper called Defining Hormesis with my colleague Linda Baldwin. And in it, we more or less summarize some of the things that I'm talking about right now, and that is the quantitative features that hormesis could be both positive and negative, depending upon the circumstances. And during that time period, during the 90s, I'm going to say there was a big explosion in toxicology dealing with endocrine disruptor chemicals.