#472 Scientist Reveals the Hidden Program of Aging and How to Control It - Josh Mitteldorf PhD

Josh Mitteldorf (0:00)

The message here is that the organism isn't trying to live as long as possible, but we're trying to live as long as possible. The more food it has, the more resources, the easier its life is, the better a job it would do. No, when life is easy, when you don't have to exercise, you don't have to work, when the temperature is just right, when you don't have any toxins in the environment, when you have plenty to eat, that's when life is shortest. Aging is terrible for fitness, yet aging seems to have been selected by evolution. And it's not just an accident.

Siim Land (0:32)

Dr. Josh, welcome to the show.

Josh Mitteldorf (0:34)

Thanks for having me. Delighted to be here. Isn't that what everybody says?

Siim Land (0:40)

Yeah, and we just said that everyone is excited as well to have the guest on the podcast with an amazing guest every time, which is true in my opinion this time because you've written quite an interesting and thought-provoking book about aging and longevity, which we're gonna get into. But my first initial question would be, you have a background in physics, you started off in physics, so what made you, I guess, a pivot or get more interested in aging research?

Josh Mitteldorf (1:12)

Well, I'll comment first that all of the revolutionary changes come from somebody outside the science. And in particular, all of the big insights that have changed biology have come from people who aren't biologists coming into the field and say, oh, you got that wrong. So I'm in a good tradition without comparing myself to some of the real bright lights in the field. I mean, Schrodinger came in and predicted DNA in 1948 or something, long before there was knowledge of what DNA was.

Haldane, there are many good examples of people coming into physics and offering insights into biology. So yes, I was a physicist before I was a biologist. It was 1996 I read an article in Scientific American by Weindrück describing caloric restriction experiments, and that this wasn't just an anomaly with mice. Every organism they tried it with, the less they feed them, the longer they live. And I thought, the message here is that the organism isn't trying to live as long as possible. If it were trying to live as long as possible, then the more food it has, the more resources, the easier its life is, the better a job it would do. No, when life is easy, when you don't have to exercise, you don't have to work, when the temperature is just right, when you don't have any toxins in the environment, when you have plenty to eat, that's when life is shortest. So whatever it is that's causing the limit of lifespan, it's not that the organism is trying to do its best, but there are just these things in its way. So that was the initial insight. Before I knew anything else, I had a sense aging is an inside job. 1996

Siim Land (3:17)

Yeah, you're describing these examples of calorie restriction that pretty universally across all species have been shown to extend lifespan. And I think the longest life extension in history comes from calorie restriction a few decades ago, where it was up to like 65% life extension through calorie restriction in mice, which is kind of interesting. Yeah, that you would predict that an abundance of resources would extend lifespan, but it actually that mild restriction or, you know, let's say these positive stressors, which is in biology is called hormesis, that these minor stressors. Yeah.

Josh Mitteldorf (4:00)

So it's just an example. Caloric restriction is just one example of hormesis, and there are many others. Even radiation, I mean, you think of radiation as toxic. It causes free radicals, it kills cells.

If anything should shorten lifespan is radiation, and it does if you get a high enough dose, but low dose radiation increases lifespan against all of our expectations.

Siim Land (4:29)

Yeah, and you know, sunlight is a form of mild radiation that is healthy and needed for optimal health in some amounts. But you mentioned that aging, or at least in your book, you talk about how aging is more like programmed into the organism. That, or what is like evolutionary, why did we evolve to age? What is the reason it happens in the first place?

Josh Mitteldorf (4:57)

Well, there's the paradox that I realized right away in 1990s. So I didn't know anything about how evolutionists think. I didn't know about the selfish gene. I didn't know that there's no such thing as group selection. It's only individual selection. But in 96, I had this idea. I wrote it up and remember, there was no spam in 1996 There were people on listservs and they were academic. They expected that anybody who was coming to them on this listserv is sincere, and not trying to sell them something, not trying to scam them, the good old days on the Internet. So 1996, I wrote up the ideas that I just described to you, that aging must be an inside job based on this. I sent it out to a listserv of several thousand evolutionary biologists and I got dozens of responses. Of course, you wouldn't have that experience today. People would just send you a message to the spam folder today. But in 1996, I got dozens of responses and they were all telling me the same thing. No, you don't understand. It's not possible for evolution to positively select for a shorter lifespan. Fitness is about living a long time and having more offspring. That's what fitness is. We know this is a matter of theory and it's called the selfish gene theory or neo-Darwinism or sometimes called the new synthesis, although new means it was new in 1930