November 30, 2012

Immortal Jellyfish can reverse aging and rejuvenate itself at any point

NY Times - The scientists described how the species (the immortal jellyfish - Turritopsis) — at any stage of its development — could transform itself back to a polyp, the organism’s earliest stage of life, “thus escaping death and achieving potential immortality.” This finding appeared to debunk the most fundamental law of the natural world — you are born, and then you die.

One of the paper’s authors, Ferdinando Boero, likened the Turritopsis to a butterfly that, instead of dying, turns back into a caterpillar. Another metaphor is a chicken that transforms into an egg, which gives birth to another chicken. The anthropomorphic analogy is that of an old man who grows younger and younger until he is again a fetus. For this reason Turritopsis dohrnii is often referred to as the Benjamin Button jellyfish.

Yet the publication of “Reversing the Life Cycle” barely registered outside the academic world. You might expect that, having learned of the existence of immortal life, man would dedicate colossal resources to learning how the immortal jellyfish performs its trick. You might expect that biotech multinationals would vie to copyright its genome; that a vast coalition of research scientists would seek to determine the mechanisms by which its cells aged in reverse; that pharmaceutical firms would try to appropriate its lessons for the purposes of human medicine; that governments would broker international accords to govern the future use of rejuvenating technology. But none of this happened.

Some progress has been made, however, in the quarter-century since Christian Sommer’s discovery. We now know, for instance, that the rejuvenation of Turritopsis dohrnii and some other members of the genus is caused by environmental stress or physical assault. We know that, during rejuvenation, it undergoes cellular transdifferentiation, an unusual process by which one type of cell is converted into another — a skin cell into a nerve cell, for instance. (The same process occurs in human stem cells.) We also know that, in recent decades, the immortal jellyfish has rapidly spread throughout the world’s oceans in what Maria Pia Miglietta, a biology professor at Notre Dame, calls “a silent invasion.”

But we still don’t understand how it ages in reverse. There are several reasons for our ignorance, all of them maddeningly unsatisfying. There are, to begin with, very few specialists in the world committed to conducting the necessary experiments. “Finding really good hydroid experts is very difficult,” says James Carlton, a professor of marine sciences at Williams College. [1 or 2 per country]

There is just one scientist who has been culturing Turritopsis polyps in his lab consistently. He works alone, without major financing or a staff, in a cramped office in Shirahama, a sleepy beach town in Wakayama Prefecture, Japan, four hours south of Kyoto. The scientist’s name is Shin Kubota, and he is, for the time being, our best chance for understanding this unique strand of biological immortality.

Kubota, however, has no such compunction. “Turritopsis application for human beings is the most wonderful dream of mankind,” he told me the first time I called him. “Once we determine how the jellyfish rejuvenates itself, we should achieve very great things. My opinion is that we will evolve and become immortal ourselves.”

The world’s only captive population of immortal jellyfish lives in petri dishes arrayed haphazardly on several shelves of a small refrigerator in Kubota’s office. Like most hydrozoans, Turritopsis passes through two main stages of life, polyp and medusa. A polyp resembles a sprig of dill, with spindly stalks that branch and fork and terminate in buds. When these buds swell, they sprout not flowers but medusas. A medusa has a bell-shaped dome and dangling tentacles. Any layperson would identify it as a jellyfish, though it is not the kind you see at the beach. Those belong to a different taxonomic group, Scyphozoa, and tend to spend most of their lives as jellyfish; hydrozoans have briefer medusa phases. An adult medusa produces eggs or sperm, which combine to create larvae that form new polyps. In other hydroid species, the medusa dies after it spawns. A Turritopsis medusa, however, sinks to the bottom of the ocean floor, where its body folds in on itself — assuming the jellyfish equivalent of the fetal position. The bell reabsorbs the tentacles, and then it degenerates further until it becomes a gelatinous blob. Over the course of several days, this blob forms an outer shell. Next it shoots out stolons, which resemble roots. The stolons lengthen and become a polyp. The new polyp produces new medusas, and the process begins again.

“There’s a shocking amount of genetic similarity between jellyfish and human beings,” said Kevin J. Peterson, a molecular paleobiologist who contributed to that study, when I visited him at his Dartmouth office. From a genetic perspective, apart from the fact that we have two genome duplications, “we look like a damn jellyfish.”

This may have implications for medicine, particularly the fields of cancer research and longevity. Peterson is now studying microRNAs (commonly denoted as miRNA), tiny strands of genetic material that regulate gene expression. MiRNA act as an on-off switch for genes. When the switch is off, the cell remains in its primitive, undifferentiated state. When the switch turns on, a cell assumes its mature form: it can become a skin cell, for instance, or a tentacle cell. MiRNA also serve a crucial role in stem-cell research — they are the mechanism by which stem cells differentiate. Most cancers, we have recently learned, are marked by alterations in miRNA. Researchers even suspect that alterations in miRNA may be a cause of cancer. If you turn a cell’s miRNA “off,” the cell loses its identity and begins acting chaotically — it becomes, in other words, cancerous.

Hydrozoans provide an ideal opportunity to study the behavior of miRNA for two reasons. They are extremely simple organisms, and miRNA are crucial to their biological development. But because there are so few hydroid experts, our understanding of these species is staggeringly incomplete.

“Immortality might be much more common than we think,” Peterson said. “There are sponges out there that we know have been there for decades. Sea-urchin larvae are able to regenerate and continuously give rise to new adults.” He continued: “This might be a general feature of these animals. They never really die.”

“It’s important to keep in mind that we’re not dealing with something that’s completely different from us,” Martínez told me. “Genetically hydra are the same as human beings. We’re variations of the same theme.”

As Peterson told me: “If I studied cancer, the last thing I would study is cancer, if you take my point. I would not be studying thyroid tumors in mice. I’d be working on hydra.”

Hydrozoans, he suggests, may have made a devil’s bargain. In exchange for simplicity — no head or tail, no vision, eating out of its own anus — they gained immortality. These peculiar, simple species may represent an opportunity to learn how to fight cancer, old age and death.

But most hydroid experts find it nearly impossible to secure financing. “Who’s going to take a chance on a scientist who doesn’t work on mammals, let alone a jellyfish?” Peterson said. “The granting agencies are always talking about trying to be imaginative and reinvigorate themselves, but of course you’re stuck in a lot of bureaucracy. … The pie is only so big.”

The most reliable way to make the immortal jellyfish age in reverse, Kubota explained to me, is to mutilate it. With two fine metal picks, he began to perforate the medusa’s mesoglea, the gelatinous tissue that composes the bell. After Kubota poked it six times, the medusa behaved like any stabbing victim — it lay on its side and began twitching spasmodically. Its tentacles stopped undulating, and its bell slightly puckered. But Kubota, in what appeared a misdirected act of sadism, didn’t stop there. He stabbed it 50 times in all. The medusa had long since stopped moving. It lay limp, crippled, its mesoglea torn, the bell deflated. Kubota looked satisfied.

“You rejuvenate!” he yelled at the jellyfish. Then he started laughing.

We checked on the stab victim every day that week to watch its transformation. On the second day, the depleted, gelatinous mess had attached itself to the floor of the petri dish; its tentacles were bent in on themselves. “It’s transdifferentiating,” Kubota said. “Dynamic changes are occurring.” By the fourth day the tentacles were gone, and the organism ceased to resemble a medusa entirely; it looked instead like an amoeba. Kubota called this a “meatball.” By the end of the week, stolons had begun to shoot out of the meatball.

This method is, in a certain sense, cheating, as physical distress induces rejuvenation. But the process also occurs naturally when the medusa grows old or sick. In Kubota’s most recent paper on Turritopsis, he documented the natural rejuvenation of a single colony in his lab between 2009 and 2011. The idea was to see how quickly the species would regenerate itself when left to its own devices. During the two-year period, the colony rebirthed itself 10 times, in intervals as brief as one month. In his paper’s conclusion, published in the journal Biogeography, Kubota wrote, “Turritopsis will be kept forever by the present method and will . . . contribute to any study for everyone in the future.”

He has made other significant findings in recent years. He has learned, for instance, that certain conditions inhibit rejuvenation: starvation, large bell size and water colder than 72 degrees. And he has made progress in solving the largest mystery of all. The secret of the species’s immortality, Kubota now believes, is hidden in the tentacles. But he will need more financing for experiments, as well as assistance from a geneticist or a molecular biologist, to figure out how the immortal jellyfish pulls it off. Even so, he thinks we’re close to solving the species’s mystery — that it’s a matter of years, perhaps a decade or two. “Human beings are so intelligent,” he told me, as if to reassure me. But then he added a caveat. “Before we achieve immortality,” he said, “we must evolve first. The heart is not good.”

By heart, he meant the human spirit.

“Human beings must learn to love nature,” he said. “Today the countryside is obsolete. In Japan, it has disappeared. Big metropolitan places have appeared everywhere. We are in the garbage. If this continues, nature will die.”

Turritopsis, it turns out, is also very weak. Despite being immortal, it is easily killed. Turritopsis polyps are largely defenseless against their predators, chief among them sea slugs. They can easily be suffocated by organic matter. “They’re miracles of nature, but they’re not complete,” Kubota acknowledged. “They’re still organisms. They’re not holy. They’re not God.”

And their immortality is, to a certain degree, a question of semantics. “That word ‘immortal’ is distracting,” says James Carlton, the professor of marine sciences at Williams. “If by ‘immortal’ you mean passing on your genes, then yes, it’s immortal. But those are not the same cells anymore. The cells are immortal, but not necessarily the organism itself.” To complete the Benjamin Button analogy, imagine the man, after returning to a fetus, being born again. The cells would be recycled, but the old Benjamin would be gone; in his place would be a different man with a new brain, a new heart, a new body. He would be a clone.

Fiction that relates. Benjamin Button grows younger

Dr Who Regenerates a new self after taking fatal damage

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