One day, out of the blue, I received a telephone call from two marine biologists in Wales. As I recall, they said something like “Hello there, Dr. Austad. We are marine biologists who study clams that live a very long time. Would you like to collaborate with us to investigate how they do it?”
As a biologist of aging who is perhaps best known for making a wager that the first 150-year-old person is already alive, I get a fair number of crank calls and emails from people who want to live forever—or already know how to live forever and just want my help in spreading the word. Being polite in this case, I recall my answer was something like “Possibly. What do you mean by ‘a very long time’?”
I held the telephone away from my ear. It was a transatlantic call. Maybe I had misheard. “Sorry, I thought you said ‘centuries.’”
“Yes, that’s right—centuries.”
A few months later, two researchers from Bangor University sat in my office, telling me about the longevity of bivalves—animals with hinged shells (valves), including clams, oysters, scallops, and mussels. I learned that the researchers could determine the precise age—to the year—of any individual clam. They called it sclerochronology—literally, dating things by hard parts. The word was modeled on dendrochronology, the dating of trees by their annual growth rings. Bivalve species residing in waters with seasonal changes in temperature and/or food availability develop annual growth rings in the shell. If the lives of two clams overlap, scientists can align their series of wider and narrower rings and so backdate their birth as well as death dates. By comparing series of rings from successively older shells, scientists have been able to identify shells of clams born as far back as A.D. 649.
Sclerochronology allowed scientists to discover Ming, the oldest clam ever. Ming was an ocean quahog (Arctica islandica), also known as the mahogany quahog. Arctica lives on the continental shelves on both sides of the north Atlantic Ocean. They appear to prefer cool to cold water, and they rarely live where the sea temperature exceeds roughly 16°C (61°F). This particular celebrity clam was anointed Ming—Ming the Mollusk—in the press after its great age was discovered, because it was born during China’s Ming dynasty, in 1499. To put that in perspective, at the time of its birth, Leonardo da Vinci had just finished painting The Last Supper. Christopher Columbus was in the midst of his third voyage to the so-called New World. Copernicus had not yet published his radical theory that the Earth orbited the sun, rather than vice versa. Shakespeare would not be born for another 65 years.
Ming spent the first part of its youth, as do all clams, aimlessly wandering in the water column, before finally settling down in about 80 meters (260 feet) of water just off the north coast of Iceland. It lived through the remainder of the Little Ice Age and Iceland’s centuries-long transformation from a rural, sparsely populated country into one of the most highly technological societies in the world. Ming also lived through the rise of science, until science killed it in 2006 to extract whatever historical information it could provide: Bivalve sclerochronology requires examining a shell in cross-section, which is possible only after the inhabitant has been removed—or, as we biologists like to put it, sacrificed. Ming’s remains were buried at sea. In case you are not keeping count, that made Ming 507 years old when it was sacrificed in service of science.
As a group, bivalves may be the longest-living animals. Numerous species have been documented to live a century or longer, including the Pacific geoduck clam (168 years) with its ridiculously long siphon, the freshwater pearl mussel (190 years), and the recently discovered giant deep-sea oyster—which does not have growth rings but has been radiocarbon-dated, with all the uncertainty that implies, to more than 500 years. Why these creatures live so long remains a great mystery—or really, the great mystery, as far as my own research is concerned. Explanations abound, and each possibility offers a tantalizing clue as to the basis of longevity. A better understanding could help reveal how a whole variety of animals, from bivalves to tubeworms to sharks, stave off aging. Their secrets might in turn point toward science that would help extend the lives of the creatures we care about most: us.
Bivalves’ long lives could be thanks to certain natural traits they have, the environments they live in, or the ways they act—or, perhaps most likely, some combination of all three. Like many long-lived animals, bivalves are ectothermic, or cold-blooded, drawing heat from their surroundings rather than producing it themselves. Ectothermic creatures, especially those living in cold environments, might sidestep two processes that could play a role in aging: Some biologists believe that their bodies, because they don’t heat themselves, produce fewer oxygen radicals—toxic molecules that are the byproduct of mitochondrial activity and have long been proposed as a cause of aging. They may also have lower rates of protein misfolding. (Proteins require complex, origami-like folding to perform their proper functions, and the loss of this precise folding over time may contribute to aging.)
Bivalves also have low metabolic rates, which likely yield similar benefits; most bivalves hunker down and seldom move as adults. Arctica, which has a particularly slow metabolic rate even among bivalves, is one of the slowest-growing species known. It also seems exceptional among bivalves in its ability to survive low oxygen levels: Arctica have survived for two months in the complete absence of oxygen, helped by their ability to reduce their metabolism to a tiny fraction (perhaps as little as 1 percent) of the normal rate for up to a week.
Life in the cold, which can also decrease rates of oxygen-radical production and protein misfolding, may play a role for some clams as well. Ming, for instance, lived in water that was about 6 to 7 degrees Celsius (43 to 45 degrees Fahrenheit). In warmer water, Arctica do seem shorter-lived. In the Baltic Sea, for instance, they don’t appear to live longer than 50 years, although it is unclear whether this is due to the Baltic’s warmer temperatures, the low and variable salinity as a result of all the rivers that empty into it, pollution from those rivers, or the sea’s shallowness (it has an average depth of 55 meters, or 180 feet), with all the environmental instability that entails. And there may be clams around cold seeps or on the Antarctic sea bottom that make Ming look like a whippersnapper. We just don’t know.
Another likely benefit: Many bivalves live pretty safe lives. The ocean, once you get beyond the surface layers, is a relatively stable place to live. The deeper you go, the more you’re shielded from abrupt environmental changes. Moreover, the longer a bivalve lives, the larger and thicker its shell grows, thus gradually reducing the number of potential predators that can break through it. Many species of bivalves also live partially or fully submerged in the muck of the sea bottom, which makes things even safer.
If these factors help explain the exceptional longevity of some bivalve species, we might expect their opposite to predict short life—even in bivalves. For instance, if there were bivalve species that lived in warm, shallow, less stable surface waters and exposed themselves to dangers by, say, actively swimming (which would also require a higher metabolic rate), you might expect that they would be short-lived. Yes, such clams exist: The bay scallop lives in warm, shallow water. And, in fact, it lives only a year or two.
The nice thing about most of these long-lived—as well as short-lived—bivalves is that they can be brought into the laboratory and studied. My colleagues and I have been doing this for some time. Although we can’t yet claim to have discovered the secret to their 500-year lifespan, we have investigated two existing theories.
First, if longevity is related to the ability to resist damage from oxygen radicals, as many scientists believe, Ming would have been well protected. We know this because one summer, at the Marine Biological Laboratory in Massachusetts, my students and I investigated how well different bivalve species could survive oxygen-radical stress. Nearby fishing boats sold us some Arctica. We also bought some table clams, which can live up to a century; several other clam species that live about 20 years; and some bay scallops. Then we added some oxygen-radical-generating chemicals to their tanks and recorded what happened. The results were remarkable. The normally short-lived bay scallops all died within two days. The 20-year clams died by day five. It took 11 days for half of the 100-year table clams to die. Yet the Arctica seemed unfazed. After two weeks, they remained alive and seemed, well, happy as a clam. We tried several other chemicals that damaged cells in various ways, with similar results. These observations confirmed what had been seen in standard laboratory animals: Animals that lived longer could tolerate greater assaults from the damaging byproducts of life, such as oxygen radicals. Understanding the nature of that greater tolerance could potentially teach us something about how to live longer in good health.
The second thing we discovered about Arctica was delicious in its irony. Even though clams lack anything that could reasonably be called a brain, Arctica might just hold a therapeutic key to Alzheimer’s disease. We wanted to investigate whether Arctica have better protections against protein misfolding. When proteins become misfolded, they not only can no longer perform their normal cellular function, but they become sticky and clump together. The familiar plaques and tangles in the brain—hallmarks of Alzheimer’s disease—are clumps of sticky, misfolded proteins. We applied a number of well-known methods for purposely misfolding proteins to the liquid cellular extract of clam species that lived only up to seven years, along with another species that lived up to 30 years, another living 100 years, all the way to Arctica, the 500-year species. We found that no matter how many ways we tried, proteins from the Arctica resisted, to a great extent, our attempts to misfold them. Arctica’s protein-protection machinery worked better than any other clams’. In fact, it worked better than a similar extract from human tissue with any protein we tried. We even tried it on human A-beta, the protein that makes Alzheimer’s plaques.
At this point, we began to get very excited. If we could isolate the molecule or molecules in Arctica’s protein-maintenance machinery responsible for this exquisite ability to resist misfolding, we might be able to use that knowledge to develop treatments for protein-misfolding diseases such as Alzheimer’s and Parkinson’s disease. For the past seven years, we have been searching for the secret to Arctica’s ability to prevent protein misfolding. We have been highly successful at discovering a number of things that aren’t responsible. Alas, to date, we have not been able to figure out what is. We will keep working on it, though. Science is seldom quick or easy.