The mysterious life of the world’s oldest mole rat: Challenging death, about to eat his birthday at an age 9 times older than his fellow humans

Joe looks noticeably older, compared to the day he was born, in 1982. He now looks ruddy, cross-eyed, and lined with wrinkles. Its teeth have also become strange, with incisors located on the outside of its lips to push dirt out of its mouth when it needs to dig tunnels to accommodate its tubular body.

Rochelle Buffenstein, a biologist, met Joe when he began studying naked mole rats in the 1980s, during her PhD in Cape Town, South Africa. Her research concerns the metabolism of vitamin D in mole rats, as they spend all their time in dark tunnels, far from the sun. But then she moved to another city, Johannesburg to start her job, leaving Joe behind. The mole Joe was later transferred to the Cincinnati Zoo. No one thought that the two would reunite anytime soon.

In the late 1990s, Buffenstein noticed something strange. The mole rats she had studied were not dead yet.

“They’re over 15 years old, by rodent standards that’s a long life,” Buffenstein said. “So I thought, ‘Well, they should only live up to six years.’ And now it’s living more than double its maximum lifespan.”

She then turned to the study of aging, knowing that the area was important but understudied. In the early 2000s, Joe’s “other half” at the zoo passed away and this “guy” needed a new mate. Buffenstein offers to help it start a new life at his lab in New York. Since then, this naked mole rat has joined Buffenstein in research papers everywhere.

Today, Joe is still a rodent with wrinkled skin and a taste for vegetables. But it is currently Buffenstein’s oldest naked mole rat, as well as the oldest mouse ever recorded. This year, Joe turns 39 years old. It is at an age 9 times longer than the life span of normal mice and 5 times longer than other similarly sized rodents.

When Buffenstein began studying the age of naked mole rats, she wanted to take a sort of before-and-after image of their biology, to determine when bones, organs or even levels. Their antioxidant properties change. But she kept waiting, and waiting, and then waiting again because nothing happened.

“It’s very frustrating. Because you want to see this change happen, so you can dig into what’s changed later.” Buffenstein said.

Back then, Buffenstein was one of the few researchers who took moles and the aging process seriously. And now, mole rats are taking over all the halo, and laboratories around the world are working to uncover their underlying biology, with the goal of using those insights to develop new drugs. A drug that can stop the ravages of aging in humans.

Because humans and gorillas have high blood pressure. Rats and seahorses have cancer. Kangaroos and dogs have arthritis again. An endless list of diseases caused by aging, an endless list of animals. That “and” is so common that any “but” makes scientists frown. Joe is a prominent “but” among them. This mole is enjoying an incredibly long and healthy life.

“Naked moles seem to say that aging is not inevitable.” Buffenstein, who currently works for Google’s biotech division, Calico Labs, specializes in research and development of solutions to combat aging and related diseases. “But they clearly have a blueprint for stopping the aging process.”

But what is that plan? It may be that their cells are filled with protective molecules, or that a large set of genes are turned on or off unexpectedly, or that the structure of their immune systems, organs or cell membranes is complete. totally different. Naked mole rat researchers have yet to uncover the secret behind this amazing age. Maybe their unique anti-aging tricks will help prolong people’s lives – or maybe everything is just an inevitable dead end.

The mysterious life of the world s oldest mole rat Challenging death about to eat his birthday at an age 9 times older than his fellow humans | Discover

Joe is aging, but at a super slow aging rate.

Joe is getting old, so are people. As you age, cellular function declines, making the body more susceptible to disease and eventually death. Your DNA accumulates damage due to oxidizing molecules, which also attack proteins and fats, ripping you apart from the inside. Cells that “get older” stop reproducing. The reserve of rejuvenating stem cells is gradually depleted. Communication between cells is disrupted and inflammation increases. There is no single driving force behind cellular aging, because it is a network of feedback loops. Enzymes read genes like a grocery list, of different proteins to prepare, and those proteins can protect that enzyme, that gene, or some process throughout the body. Your body is programmed to tolerate bumps and bruises.

“While we’re young, that fix actually works almost flawlessly”, said Vera Gorbunova, a prebiologist who studies mole rats at the University of Rochester. “However, as the aging process begins to occur, repair becomes problematic. Gene reading enzymes falter, proteins are misfolded, radioactive mitochondria weaken muscles and cancer development”.

What begins life as a balanced cycle of mistakes and corrections, turns into a rickety wooden roller coaster – hurled by rusty machinery and makeshift repair processes – prone to jolt and up the road to hell. As damage from aging builds up, things also speed up.

There’s something called Gompertz’s law of mortality, a mathematical model that quantifies how the intrinsic risk of death increases exponentially as an animal ages. Although life expectancy varies for different species, the shape of the Gompertz curve is normative. A lab rat’s risk of dying doubles every three months or so. For a dog, that’s about every three years. When a person turns 25, their risk of death doubles every 8 years. But naked mole rats don’t “play” by these rules.

The mysterious life of the world s oldest mole rat Challenging death about to eat his birthday at an age 9 times older than his fellow humans | Discover

Graph showing Gompertz’s law of death.

In 2018, Buffenstein and her colleagues at Calico published a paper showing naked mole rats defying Gompertz’s law of death. Even at the age of 35, Joe still does not have statistics showing that his risk of death has been twice as high as when he was 2 years old. Of course, naked mole rats still die, but the risk is very low.

No one knows if the behavior of the mole rats hides a secret related to the aging process. For one thing, they are highly social, a rarity among mammals. That means that in a colonial area there will be one queen in charge of the entire infection. It will mate with up to three males and remain fertile even 30 years after puberty. For a human, that is the equivalent of giving birth at the age of 300.

Joe has witnessed the ups and downs of moles. It and its colony mates have spent years cleaning the nest, tending to the queen, and defending against strange intruders. But most of the time they lead a relatively healthy life, in part because they live in deep burrows in the desert, where there are few natural predators.

So what can kill a naked mole rat? Martha Delaney, a veterinary pathologist at the University of Illinois said: “They beat each other. Naked moles are extremists. They’ll attack strangers, push and bite each other, and banish members like outcasts.”

The mysterious life of the world s oldest mole rat Challenging death about to eat his birthday at an age 9 times older than his fellow humans | Discover

Scientists are looking for ways to uncover the “eternal” secret of this rodent.

Melissa Holmes thinks they are adorable animals. Holmes is a behavioral neuroscientist at the University of Toronto who has worked with more than 1,000 naked mole rats. Working within the odd social structure of moles has earned them a reputation for aggression, but according to her, for animals that live in large groups, moles are generally very stable and peaceful. Holmes also had a group of moles of his own to follow over the course of 12 years. And some of them have never been injured in a fight.

And it’s not that the naked mole rat never gets old or sick. But their bodies somehow slow down these processes. Whereas the bones of typical mammals become brittle and thinner over the years, mole bones retain their mineral content and remain as solid. People tend to gain more fat with age. The naked mole rat is not.

“But the system stands out the most”, According to researcher Buffenstein, “is the cardiovascular system”.

Human veins and arteries often harden over time. The stiffer those vessel walls, the harder the heart has to pump. It leads to increased blood pressure. There is also an increased risk of death. The blood vessels of the naked mole rat remain active throughout life. She said: “Every measure we’ve looked at of heart function hasn’t changed from 6 months to 24 years later”

In humans, heart disease is the leading cause of death. Cancer ranks second. About 40% of Americans develop cancer in their lifetime. For naked mole rats, this probability is less than 1%. In a 2008 study, Buffenstein reported that there was no cancer in a group of 800 mole rats. As of 2021, Buffenstein says she has found only five cancers in more than 3,000 deaths.

“They’re very well adapted, like a physiological wonder,” Researcher Delaney also shares the same view…

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