02/02/2018

The Naked Mole Rat Defies The Laws Of Aging

9:41 minutes

A naked mole rat peeks out of a hole.
A naked mole rat peeks out of a hole. Credit: Shutterstock

The naked mole rat has been boggling the minds of scientists for many years now. What it lacks in conventual cuteness it makes up for with some superpower-like qualities. It can survive for 18 minutes without oxygen. It’s practically immune to cancer. But perhaps it’s most notable characteristic is that the naked mole rat can live longer than any animal its size…up to 30 years or more.

And now scientists have discovered one more thing about this rodent’s abnormally long life—its chances of dying don’t increase over time. For most mammals, the rate of mortality increases along with age once the animal reaches adulthood (referred to as the Gompertz-Makeham law of mortality). For example, in humans, our risk of dying roughly doubles every year after turning 30. For naked mole rats, death is random.

[What do chocolate, diamonds, and snowflakes have in common? Crystals!]

“We’ve got as much chance of finding a one-year-old [mole rat] that has died as finding a 25-year-old that has died,” says Dr. Rochelle Buffenstein, Senior Principal Investigator at Calico. She joins Ira to discuss what she discovered digging into data on the naked mole rat.


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Segment Guests

Rochelle Buffenstein

Rochelle Buffenstein is a Senior Principal Investigator at Calico in San Francisco, California.

Segment Transcript

IRA FLATOW: The naked mole rat has been boggling the minds of scientists for many years now. What it lacks in conventional cuteness, it makes up for with a whole bunch of superpowers like [? koalas. ?] Let me tell you about them.

It can survive for 18 minutes without oxygen. It’s practically immune to cancer. And it’s most notable characteristic, it can live longer than any animal it’s size, up to 30 years or more.

And now scientists have discovered one more thing about the naked mole rat’s abnormally long life. Its chance of dying does not increase over time. You heard me correctly.

Joining me to explain what this all means is my guest, Dr. Rochelle Buffenstein. She’s a comparative biologist and Senior Principal Investigator at Calico Labs in San Francisco. Welcome to Science Friday.

ROCHELLE BUFFENSTEIN: Thank you. I’m delighted to be here.

IRA FLATOW: This doesn’t mean that the naked mole rat is immortal, does it?

ROCHELLE BUFFENSTEIN: No, absolutely not. It means that its chance of dying, if it were one year of age or 30 years of age, is exactly the same. So unlike the Laws of Gompertz, who was a mathematician in the early 1800s who discovered that humans show a doubled risk of dying every eight years beyond the age of about 35 to 40. And so you know that a 20-year-old has a much greater chance of surviving for the next 30 years than, say, a 50-year-old has.

Based on his life tables that he did on British people living in various cities, he came up with a law called the Gompertz-Makeham law of mortality, which has basically been replicated in horses, dogs, sheep, mice, every other species that has been looked at to date. And so we started looking at studies on naked mole rats based on 30 odd years worth of data that we’ve collected. And my colleague, Graham Ruby, who’s a bioinformatics computer scientist, took these data and really analyzed them very rigorously in terms of the Gompertzian relationships and showed that mole rats showed the same risk of dying if they were two years of age or if they were 30 years of age. There was no change, which was remarkable.

IRA FLATOW: You know that to lay people that makes no sense, right? I mean, you get older and older and older, your chance of dying is no greater when you’re older than when you were younger. And yet, the naked mole rat does not live forever.

ROCHELLE BUFFENSTEIN: No, but its death is random. It’s almost like radioactive decay. It’s a stochastic mechanism rather than that kind of phenomena. It’s almost like the elves in Lord of the Rings, which in the various fights they had landed up all dying almost at the same time, not because they were old, but because of the conditions in which they were encountering battles and the likes thereof.

IRA FLATOW: So how do you attribute this statistical anomaly to the naked mole rat? Why is it defy the Gompertz mortality law when everything else has to tout to it, kowtow to it?

ROCHELLE BUFFENSTEIN: I think a lot of their basic biology contributes to the fact that they live in an environment which may lend itself to really harsh conditions that they have to survive. Otherwise the species would become extinct. And they have some strange behavioral patterns in that they’re eusocial. They restrict breeding to one female in the colony and a few males in the colony. They live in a desert environment where food is really hard to find, but they’re nevertheless protected from a whole range of things that would influence mortality in the wild.

IRA FLATOW: So what is the expected life of a newborn naked mole rat?

ROCHELLE BUFFENSTEIN: That’s a trick question because a newborn mole rat has quite a high incidence of dying in the first couple of weeks of life.

IRA FLATOW: Oh, I didn’t know that.

ROCHELLE BUFFENSTEIN: They get eaten by their parents. Not a very nice phenomena. Or they might not get sufficient milk.

And after they’ve survived three months, they pretty much have the same risk of dying as a 20-year-old animal. It’s from three months to 30 years or so that we see no change in mortality rate. But they do, in their first couple of weeks, maybe go through survival of the fittest. And then the rest that survive are going to do well.

IRA FLATOW: This is Science Friday from PRI, Public Radio International talking with Dr. Rochelle Buffenstein of Calico about the life expectancy of the naked mole rat. You have been studying them for some time. Your entire career. Is that correct?

ROCHELLE BUFFENSTEIN: I’ve been studying them almost my entire career in between other studies. I’ve worked on multiple species, including humans, but I constantly come back to the naked mole rats. I collected them while I was a student in South Africa in 1980. And I’ve been fortunate enough to have my colony of mole rats move with me to various places with every job that I’ve taken on here.

IRA FLATOW: So what do you find so fascinating about them? Is it just their longevity? You must find something really intriguing.

ROCHELLE BUFFENSTEIN: Initially, I was more interested in how they control their vitamin D metabolism, given that they live permanently in the dark. And we know that vitamin D is so integral for cell proliferation, for bone, and all those kind of things.

And with every study, it came apparent the animals are sort of defying the dogmas and doing things differently. I got fascinated by the fact that they are very resistant to cancer. We’ve had only five incidences of cancer in more than 30 years of looking to see what animals are dying from and things like that. So we’ve been fascinated by all sorts of aspects of their biology, and they continue to intrigue us.

IRA FLATOW: If I were to meet a naked mole rat, would I think it was cute?

ROCHELLE BUFFENSTEIN: Beauty is in the eye of the beholder.

IRA FLATOW: You do then.

ROCHELLE BUFFENSTEIN: You may have to answer that question.

IRA FLATOW: I’m saying that I’m guessing that you do then.

ROCHELLE BUFFENSTEIN: I think each animal has its own kind of personality. And yes, I agree. They’re not the best looking animals, but when you spend time with them, they really are very cute.

IRA FLATOW: So then what more would you like to know? You’ve been studying them for decades. What would you like to know more about them?

ROCHELLE BUFFENSTEIN: Well, I’m really hooked up on why they are able to beat the odds and not get cancer and not get Alzheimer’s and not get sort of all the diseases that we associate with aging. And I’m very intrigued in trying to get a handle on the mechanisms they employ that protect them and enable them to live very healthy lives for as long as they do.

IRA FLATOW: I would think that people would be throwing money at you to study this, for those very same reasons.

ROCHELLE BUFFENSTEIN: Well, there are a lot of people who are very interested in the biology of the naked mole rat and its role in aging. And Calico has got very interested in these animals and recognized that they’re a model of exceptional bio or ontological interests. Sp I think we’re at the right place to really get to the answer of why they age so well.

IRA FLATOW: Do you have any clues, any hints genetically? Do they have a good diet? I mean, do you have any hints about what direction to go?

ROCHELLE BUFFENSTEIN: The answer’s going to be everything. My guess is that whatever your weakest link is in the system, that’s what’s going to do you in. But Graham Ruby, the first author on this paper, is studying the genetics of these animals, looking at genetic variability and genomic integrity. I think that’s a very big player in their extreme longevity.

Other aspects of their basic biology are more at the molecular biology. What are the mechanisms that help them prevent protein aggregation diseases like Alzheimer’s and other things like that? So we’re really trying to delve into cellular and molecular mechanisms to get a good handle on what it is that enables these animals to live as long and as healthy as they do.

IRA FLATOW: Well when you guys come up with the answer, will you come back on and tell us more about it?

ROCHELLE BUFFENSTEIN: Yeah, I’m happy to do so.

IRA FLATOW: We’re rooting for you because we all want to extend that life and find out. It’s our second favorite animal on the program. So I want you to come on and talk about it.

ROCHELLE BUFFENSTEIN: What’s your first?

IRA FLATOW: Tardigrades. We’ll talk more about tardigrades, and of course we always think about cephalopods. We have cephalopod week and that kind of thing. We’re adding the naked mole rat right in there with the rest of them.

ROCHELLE BUFFENSTEIN: That’s good to know.

IRA FLATOW: OK. Dr. Rochelle Buffenstein, Senior Principal Investigator at Calico Labs in San Francisco.

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