Methuselah's Zoo: What Nature Can Teach Us about Living Longer, Healthier Lives

Preface

It was opossum number 9 that hooked me. Working from a biological research station on the central Venezuelan savanna, my friend and colleague Mel Sunquist and I had begun a project to investigate how nutrition might affect whether opossums bore mostly male versus mostly female pups. I had first tagged number 9 when she was no bigger than a honeybee, hairless and eyes still shut, suckling in her mother’s pouch. More than a year later, I caught her in a cage trap. Now full adult size, I fitted her with a radio collar and then recaptured her every month for the rest of her life. At fifteen months old, she looked in perfect health, a vigorous opossum mother with eight healthy pouch young. But three months later, I was shocked to find that she had developed cataracts in both eyes. She had lost weight. The muscle along her flank had noticeably shrunk. When I released her, she wobbled along even more sluggishly than most opossums. Less than a month later, she was dead. How could she have aged so dramatically in three short months?

Up to then, I hadn’t thought much about it, but I assumed that opossums, which are about the size of a house cat, would age pretty much like a house cat. House cats—and I had had plenty of them in my pet-filled life—remain vigorous and healthy through at least their first decade or decade and a half of life. Yet here was a year-and-a-half-old opossum who looked and acted ancient. Years later, by which time I had tracked more than a hundred wild opossums from birth to death—few of them surviving to age two and none surviving even as long as age three—I dug into the sparse scientific literature to see what it said about their longevity. Wild opossums live at least seven years, that literature told me. How could what I saw—when I had followed so many individuals almost from the day they were born to the die they died—be so different from what the scientific literature claimed? Eventually, I tracked down the reason. Someone, years previously, had measured a number of opossum skulls in the Smithsonian Natural History Museum’s collection. Making assumptions about opossum’s reputed continued growth throughout life, they had calculated that the biggest skull must represent an opossum at least seven years old.

By now though, I knew wild opossums well, as well as anyone in the world. Having moved from Venezuela back to the States, I had taken a position as an assistant professor at Harvard University, where I had a large opossum longevity study underway. North American opossums also seemed elderly by no more than two years of age. But one of my radio-collared animals had grown up in an area near an open dumpster into which a local restaurant disposed of its waste food. Scavenging that food night after night, she was nearly twice the size of any other of my study opossums the same age. Aha! Now I understood how that unusually large skull in the Smithsonian collection could have misled someone.

Not long after my encounter with opossum number 9 in the wilds of Venezuela, I lost interest in whether nutrition affected whether animals had mostly male or mostly female offspring. What was going on with aging? Why did some animal species age fast and die young and others, outwardly very similar, age slowly and die old? Why couldn’t nature—which routinely performed the almost miraculous transformation of a fertilized egg into a healthy adult frog or fish or ferret—do the seemingly much easier task of maintaining that adult’s health? And could we understand more about this mysterious process of aging if we knew more about the real lives of animals in their natural habitat? The misinformation I had uncovered about opossum longevity made me curious about misinformation about other species, including our own.

That was almost forty years ago. Over the intervening decades, I have been steeped in research on why and how animals age. Although I kept my interest in how long animals could live in nature, most of my research and that of my colleagues trying to understand the biology of aging was carried out with laboratory species that were demonstrably unsuccessful at coping the aging process. They all lived fast and died young. With all the wonders of twenty-first-century cell and molecular biology, we were making spectacular progress at understanding the way these laboratory species aged. We were discovering many ways to slow the aging process in these species. But humans already age much more slowly than any of our laboratory animals. Were we learning anything relevant to keeping people healthy longer from the study of animals that lived a few weeks or a few months or a few years? Might the laboratory of nature, in which some species had evolved to be much more successful than humans at staving off the depredations of aging, have something to teach us that we would never learn from our laboratory bestiary of tiny worms, fruit flies, and domesticated mice?

That question is the genesis of this book. Combining my own passion for natural history with my professional interest in finding new ways to extend human health, I wanted to explore—in more depth and with more attention to separating fact from speculation from wishful thinking than anyone had ever done before—the details of exceptional longevity in the wild. It is only by having the actual facts that nature might lead us forward.

Without the generous help of many people, this book would not have been possible. I received no end of expert advice on species of their special expertise from biologists I have met and whose research I have admired over the years. These people include Carol Boggs, Bert Hölldobler, Laurent Keller, and Barbara Thorne for ants, termites, and other insects; Emma Teeling and Jerry Wilkinson for bats; Thane Wibbels for turtles and tortoises; and Lindsey Hazley for tuataras. Howard Snell gave me insight on all Galápagos species. Ken Dial, Geoff Hill, and Bob Ricklefs offered me their expertise on birds over the years. Stan Braude and Shelly Buffenstein provided information on naked mole-rats. For the latest information on elephants, I am grateful to Daniella Chusyd, Mirkka Lahdenperä, and Phyllis Lee. For chimpanzees, Steve Ross and Melissa Emery Thompson provided invaluable input. For information on aging fishes and sharks, I’m grateful to Allen Hia Andrews, Greg Cailliet, and Steve Campana. For dolphins and whales, information and opinions provided by Aleta Hohn, Janet Mann, Todd Robeck, Peter Tyack, and Randy Wells were particularly helpful. I am grateful to Chris Richardson and Iain Ridgway for introducing me to bivalve mollusks, the longest-lived group of animals. The people keeping records on thousands of captive animals deserve special credit as well. I am particularly indebted to Beth Autin and Melody Brooks of the San Diego Zoo, Lindsay Hazley of New Zealand’s Southland Museum and Art Gallery, Debbie Johnson of the Brookfield Zoo, Steve Ross of the Lincoln Park Zoo, and Joann Watson of the Houston Zoo. Any errors, of course, are entirely my own.

In the aging field, per se, I thank João Pedro de Magalhães, who took several decades of my own record keeping, added it to his own, systematized it all, keeps it up to date, and has made it public and searchable via his outstanding website on animal longevity, AnAge (https://genomics.senescence.info/species). For their generosity with ideas, insights, and friendship over the years, I’m particularly thankful to Nir Barzilai, Tuck Finch, Keyt Fischer, Jim Kirkland, George Martin, Richard Miller, Jay Olshansky, Arlan Richardson, Felipe Sierra, Dick Sprott, and Gary Ruvkun, my partner in crime at the Woods Hole summer course on the molecular biology of aging. I also thank many of the people above for reading large parts of this book as it was coming together, in particular Gary Dodson, Jessica Hoffman, and Veronika Kiklevich. Rick Balkin made valuable comments on the whole thing. I would also like to thank my agent, Anthony Arnove, and Bob Prior, my editor at the MIT Press, without whom this book would have been stillborn. Finally, for putting up with my disappearance for long hours while I was writing or away in the field, I thank my wife, Veronika Kiklevich, and daughters, Marika and Molly.

1 DOCTOR DUNNET’S FULMAR

I am looking at two photographs of the Scottish ornithologist George Dunnet. In the first, he is a slender, bright-eyed, twenty-three-year-old man with black, curly hair. Cupped between his hands is a bird. To the uninitiated, the bird might be indistinguishable from a seagull. Aficionados though will recognize it as a northern fulmar (Fulmarus glacialis), a relative of the albatross that can be found during its breeding season nesting along the coastal cliffs and islands of the North Atlantic Ocean. When not breeding, it spends its time far from land, soaring over the open sea. The year is 1951, and Dunnet has just begun a study of an island colony of northern fulmars that he will continue for the rest of his life.

The second picture was taken thirty-five years later (figure 1.1). The man, now age fifty-eight, has changed fairly dramatically over that time, as we all do. He is stouter, grayer, a bit more weather-beaten. He certainly no longer looks like he could carelessly bound among the cliffs of Eynhallow Island in the Orkneys, his study site. He is holding a bird in this second photo as well. Yes, it is the same bird, which doesn’t appear to have changed at all. Not only is the bird still young looking (to a human eye), but Dunnet reported that his bird was still as reproductively active as ever—something I suspect you couldn’t say of Dunnet himself. The bird was still knocking out one chick per year, as it had been for decades and as it would continue to do even after Dunnet’s death some nine years later. The bird was also still capable of working its tail feathers off. In order to continue being reproductively successful, a northern fulmar must make repeated foraging trips, some covering as much as four thousand miles, over the ocean before returning with a stomach laden with fish, squid, and shrimp to nourish its growing chick.

Figure 1.1

Ornithologist George Dunnet in 1951 at age twenty-three and 1986 at age fifty-eight. The same bird is shown in both photos. Dunnet died in 1995. The bird was last seen the year after his death.

Source: Photo courtesy of the Outer Hebrides Natural History Society.

A number of bird species live a long time, some even longer than this fulmar, as we shall see. Perhaps even more astonishing than their long lives, though, is that they continue at an advanced age to meet the enormous energy demands that their lives require, such as those long overseas flights. Birds in nature somehow seem to remain physically fit to the very end of their lives. Wouldn’t it be nice if people could do something similar?

NATURAL LIFE SPANS

The subject of this book is long life among animals in the natural world. Long life in nature is a rare trait but is broadly distributed across the animal kingdom. The book is also about how and where and by whom long life is achieved and what we might learn about keeping ourselves healthy longer from understanding how their biology allows these species such long life.

Nature imposes two general impediments to long life—impediments that most species are unable to overcome. One of these you might call environmental hazards—external threats to survival such as predators, famine, storms, drought, poisons, pollutants, accidents, or infectious diseases. We can estimate the impact of such hazards on longevity by comparing animals’ longevity in the wild with their longevity in zoos, households, or laboratories, where we pamper and protect them from these hazards.

Consider the humble house mouse (Mus musculus) in this regard. In nature, its life expectancy is three to four months. The domesticated form of the house mouse is the laboratory mouse, a mainstay of medical research. The lab mouse is the poodle to the wild house mouse’s wolf. In a well-managed laboratory colony, mice live two to three years—some eight to twelve times longer than in the wild. If you are a small, nearly defenseless mouse, nature fairly bristles with danger. Nature, however, provides serious challenges even for animals much better able to avoid them than a mouse. The raven, for instance, could seemingly fly away from many types of danger. Yet even ravens live about three times longer when protected in captivity than they do in the wild. Animals that achieve long life in the wild must have an exceptional ability to avoid or overcome environmental hazards.

The other impediment to long life is internal. We call this hazard aging. Aging—which in this book means not the simple passage of time but the progressive deterioration over time of bodily functions and defenses along with increasing susceptibility to diseases that bedevils us all—in this sense is nearly universal.

Aging occurs at vastly different rates in different animal species, though, as we can tell by comparing our own aging to that of our pets. Relative to dogs or cats, we humans age—that is, deteriorate—slowly. Yet their aging resembles ours in many ways. With time, they lose strength and endurance. Their fur grays. They get cataracts and arthritis. Their hearing fades. They more rapidly begin to suffer from internal errors that produce organ failure. I watched this happen to my first pet dog, Spot. My family got Spot when he and I were both young. I had just started school. By the time I began high school, Spot was beginning to slow down. By the time I went away to college, Spot had passed on. Similar changes happen to us, of course, but they happen many times slower. Folk wisdom tells us that one human year is equal to seven dog years.

However, we ourselves age quickly compared to some other species. Aging slowly, in addition to being able to avoid environmental dangers, is an inescapable necessity for long life in nature. Better yet, of course, would be not aging at all.

A book appeared in 1992 entitled Sharks Don’t Get Cancer.¹ The title makes quite a claim—a bogus claim, to be sure, but an eye-catching one. Sharks do get cancer. Mice get cancer, and dogs and cats and elephants get cancer. Long-lived parrots and tortoises get cancer. Every nearly species of mammal, bird, reptile, and fish that has been looked at in any depth gets cancer. This is because cancer is caused primarily by aging and almost all species age if their environment doesn’t kill them first.²

Cancer, as we all know, is cell division run amok. Most (not all though) tissues of our bodies need a continuous supply of new cells to replace worn, damaged, and discarded ones. We get those new cells from existing cells that grow and divide to produce them. The lining of your intestines, for instance, is completely replaced by new cells every two to four days. Your skin cells are replaced in a month, and your red blood cells in four months. In fact, to keep up with all this cell replacement your body, as you sit there reading this, is manufacturing about two thousand miles of new DNA per second.

Let me repeat that in case it slipped by you. Your body manufactures a rather miraculous two thousand miles of new DNA per second just to replace the DNA it lost in discarded cells! Every time a cell divides, however, and synthesizes all that new DNA for the new cell, it is susceptible to DNA copying errors called mutations. Cancer occurs when enough critical mutations accumulate in a cell’s DNA to make it lose control of its tightly regulated replication schedule. Sometime the loss of control is minor and leads only to lumps and bumps where we previously had none. Sometimes it fatally progresses to complete and unlimited loss of control, where cells keep on dividing without limit, eventually invading surrounding tissue, and spreading through the bloodstream to other parts of the body.

Ironically, considering that I am writing about long life, even normal cells (if removed from your body and grown in a culture dish) will divide only a certain number of times before permanently stopping. Cancer cells, by contrast, are immortal. For instance, cells from the cervical cancer of a woman named Henrietta Lacks were first grown in a laboratory dish in 1951 and have continued dividing ever since. The total weight of cells grown from Lacks’s original biopsy in medical laboratories is now said to have exceeded twenty tons. These HeLa cells, after the first letters of her two names, were used in the 1950s to grow polio virus in the laboratory, leading directly to the Salk polio vaccine in 1954. Still, the corrupt vitality of cancer cells is bad for a living body.

Cancer ultimately results from damage to a single, original, renegade cell, as researcher Robert Weinberg memorably phrased it, which through a series of mutations has become a raging replication machine. The body of an older animal will be composed of cells that are the products of many more divisions than the body of a younger animal. Thus, older animals’ cells will have accumulated many more mutations because when cells divide, they are most vulnerable to those DNA mutational copying errors. The more divisions, the more mutations, eventually leading to the loss of replicative control.

My statement that cancer is caused primarily by aging may be surprising given how frequently you hear about childhood cancer. Childhood cancer, without question, is a terrible tragedy when it occurs, but it is rarer than you might guess from the attention it receives. Fewer than one in two hundred cancer deaths occur in people under twenty-five years old. After that, the death rate from cancer doubles about every eight years, so that by age eighty-five, you are more than three hundred times more likely to die from cancer than you were before age twenty-five.³ Cancer incidence progressively increases with age in all species for which we have information.

Even though almost all species age and even though all species that rely on cell division to repair themselves get cancer, those facts together do not dictate that all species are similarly susceptible to cancer. We know of some species that are remarkably resistant to cancer, in fact. That sort of resistance, along with similar resistance to aging generally, turns out to be a large part of the story about why some species live for an exceptionally long time.

WHY DO WE AGE?

Why nearly every creature ages, as contrasted with maintaining youthful health forever, is one of the enduring puzzles of biology. Evolutionary biologist George Williams summed up this puzzle succinctly by noting that evolution is remarkably adept at creating from a single fertilized egg a healthy trillion-celled young adult dog or dove or dolphin. Yet it seems incapable of performing the seemingly much easier task of maintaining the health of those adults once they have been created.

Equally puzzling is why some species age rapidly, deteriorating over the course of days or weeks, whereas for other species, it takes years, decades, or in some cases even centuries. Notice that I said nearly every living creature undergoes aging. A few seemingly do not. Those species will be of special interest as we ponder whether there are keys to slowing human aging that nature in all its cleverness has provided.

Actually, we have figured out in general terms why nature seems incapable of stopping aging. We also understand in general terms why aging occurs rapidly in some species but slowly in others. Those explanations will emerge as we investigate throughout the rest of this book how exceptionally long life is distributed within the animal kingdom.

A long life in nature, we have established, requires overcoming both external and internal hazards. Failing to overcome one as compared with the other has dramatically different consequences, though. Failure to overcome environmental hazards may lead to a short life, but it will be a largely healthy life. Consider once again the humble house mouse. In the wild, it dies of cold, predation, wounds, stress, disease, exhaustion, and starvation long before aging begins to take a substantial toll on its body. To the day of its death, its muscles remain strong, its senses sharp, its mind clear. By the time a mouse dies a natural death in the laboratory where it has been protected from environmental hazards, it dies from internal failure. And that death looks very different. In the lab, aged mice are likely to be blind, deaf, weak, arthritic, paralytic, and tumor-ridden by the time they die.

Nature has supplied many species—although not the mouse—with a variety of clever stratagems for avoiding or defeating external threats. However, doing so without also dealing with the internal threat of aging may be a fool’s success. Life may be long, but at least in its latter stages, it is likely to be miserable due to the ravages of aging. This is the situation that humans currently face.

During the twentieth century, life expectancy in the economically developed countries of the world increased by about thirty years.⁴ We haven’t changed the rate at which we biologically age, however. We have simply made our environment more hospitable with better and better public health practices and increasingly sophisticated medical care. Before 1900, we were more like mice in the wild, dying of accidents or infections for the most part before significant debilitation crept in. Today, we are more like mice in the laboratory. Deaths in early life are rare. In fact, in the United States only about one person in twenty now dies before age fifty. The majority of us die from diseases of aging like cancer, heart disease, Alzheimer’s disease, stroke, and kidney or lung failure. Even if we avoid these fatal diseases, our latter years can be marked by chronic pain, vision and hearing loss, and physical frailty. Our human life span has increased faster than our health span. If that trend continues, a societal disaster awaits. Health-care systems may well collapse under the weight of the frail and ill elderly unless we can find a way to treat the aging process as we treat diseases. Some of the species discussed in this book, already more successful than we are at staving off aging, may be able to point us toward scientific approaches to do exactly that. Others may have less to teach us about human aging, but they are interesting in their own right. I personally find exceptionally long-lived animals intrinsically interesting in the same way I find birds with spectacular plumage or mammals capable of extraordinary athletic feats interesting.

As I say, some species are successful at overcoming both external and internal hazards. Consequently, they live exceptionally long as well as exceptionally healthy lives. These are the species of what I call Methuselah’s Zoo. They are the species on which we will focus—the species from which we may learn. Methuselah, as you may recall, is the longest-lived person mentioned among all the begats of the biblical patriarchs in the book of Genesis. Methuselah, the Bible claims, lived 969 years. Maybe equally remarkable, he reputedly fathered his first child, a son, at the age of 187 years. Perhaps in those days, adolescence was even more awkwardly extended than it is today. We will dig into the details of human longevity eventually, after we explore the biology of other exceptionally long-lived species.

First, however, we need to define long life so that we know it when we see it. That isn’t as straightforward as you might think.

WHAT IS A LONG LIFE?

Aristotle made the first attempt to establish patterns of longevity among different species some 2,500 years ago. From a modern perspective, it was a brilliant analysis except for one thing. Aristotle knew almost nothing about how long different animals actually lived and what he thought he knew was often wrong. For instance, he thought that mollusks—which include squid, snails, and clams—lived for only a year (he was off a few hundred-fold on that one) and that the longest-lived animals were those that had feet (humans and elephants, specifically). He was wrong about that, too. Remarkably enough—despite this primitive, often erroneous knowledge about species longevity—he noticed two major patterns that were very real.

First, he noticed that while many plants live only a year—we call these appropriately enough annuals—some plants live far longer than any animal. Specifically, Aristotle was thinking of trees. Of course, we now know, thanks to their habit of producing annual growth rings, that many tree species live for centuries, and some even for millennia. I remember vividly as a child visiting a redwood forest in northern California, and being enthralled by a display of a giant slab of wood from an ancient tree. Its growth rings were marked with various historical dates—the birth of Christ, the fall of the Roman empire, the signing of the Magna Carta, Columbus’s first voyage to America, the beginning of the Civil War, and so on. The existence of annual tree growth rings, at least for those trees that grow in seasonal environments, has allowed us to learn a great deal about tree longevity.

However, I won’t be discussing the long lives of trees or other vegetation in this book because the meaning of the longevity of trees is often difficult to grasp for the following reason. One of the oldest-known trees in the world is named Old Tjikko (figure 1.2) (exceptionally old trees like exceptionally old animals have individual names, it seems), a sixteen-foot-tall Norway spruce (Picea abies) that apparently got lost and ended up on a mountain in Sweden. Old Tjikko was 9,558 years old at last count. Yet you could easily wrap your arms around it.

Figure 1.2

Old Tjikko, the world’s oldest known tree in all its scraggly glory. The text explains why Old Tjikko, despite its age, is unlikely to teach us much about healthy aging.

Source: Photo courtesy of Petter Rybӓck.

At this point, something should seem wrong to you. Almost ten thousand years old? Only sixteen feet tall, and you can wrap your arms around it? For comparison, the General Sherman tree, the oldest living giant sequoia tree in California, is 2,500 years old, a whippersnapper by comparison, but is 275 feet tall and thirty-six feet in diameter! It would take about sixteen professional basketball players holding hands to wrap their arms around it.

The difference between these trees is that the General Sherman is what we would think of as an individual tree. Old Tjikko is something else. The visible part of Old Tjikko—the trunk, branches, needles, cones, and all—is not that old at all, maybe only a few hundred years. Norway spruce are clonal, as are many other trees, meaning the old parts are underground—a system of roots that may spread over many acres. That root system sends up shoots, maybe dozens or even hundreds of them, which we see as individual trees, but in fact, they are genetically identical cloned stems sprouting from the same root system. Old Tjikko is that kind of tree. That tree may die, but the root system lives on, continually sending up other shoots—that is, other trees. If you cut down Old Tjikko and counted the growth rings in its trunk, you’d think it was only a few hundred years old. And you would be right—for that particular stem but not for that particular plant.

Equally confusing, if you cut off one of Old Tjikko’s branches and stick it in the ground elsewhere, it might sprout and start its own new root system. How old is that plant now? Is it the age of the root system from which it originally sprang or the age of the shoot from which it was cut? It is the existing root system of Old Tjikko, which has been carbon-14 dated to almost ten thousand years old. North America’s quaking aspen is another tree of this type. A single genetic individual aspen may cover many acres, and its root system may be thousands of years old.

I am not saying that this isn’t interesting from a scientific perspective, but it is a lot different than the longevity of individual animals such as a mouse, a man, or a monarch butterfly. It is of interest from the standpoint of how vegetative reproduction and the longevity of individual plant parts relate to one another. However, I’m most interested in how animals solve the problems of external and internal threats. I also feel more comfortable with animals that don’t make me have to scratch my head to figure out whether they are really individuals and if those individuals are really old or not. So we will stick with animals in this book—animals that are clear individuals, like dogs and bees, squid, clams, and bats. We will avoid animals like those that build coral reefs. They are more like Old Tjikko in that defining their longevity will keep us tossing and turning at night.

The other pattern that Aristotle noticed was that large animals generally live longer than small ones. This turns out to be one of the most widespread and reliable patterns in nature. Among mammals this is pretty intuitive, something I think that we all expect from casual observations of animals in our daily lives. You wouldn’t be surprised to learn that whales live longer than horses. Horses, in turn, live longer than dogs, which live longer than mice, and so on. Maybe not so expected, the same pattern holds among birds. A gull lives longer than a blackbird, which lives longer than a sparrow. Among reptiles, you find the same pattern, too, as you do among amphibians, even among clams. Note that these are general patterns—not rules. There are plenty of exceptions. Some species are exceptionally long-lived for their size. Humans are one of these. Others are exceptionally short-lived for their size. Mice are one of these. To jump ahead a bit, Tyrannosaurus rex is quite the exception to the general size-longevity rule as well. So are our primate relatives. Some other species that you might not expect are particularly dramatic exceptions.

The general size effect presents us with a problem for defining exactly now to recognize a long life. Do we focus on absolute longevity (the actual number of years of life) or relative longevity (the years of life compared with other animals of the same size)? Should a naked mole-rat, which is the size of a mouse but lives more than ten times as long, be considered a member of Methuselah’s Zoo? It lives almost forty years, but that is less than a monkey, not to mention a human.

Actually, it does makes sense to consider size in defining Methuselah’s Zoo. Here’s why. Biological time flies by faster for small animals compared with large animals. Compared to a human or a horse, a mouse’s engine is revved much higher. That is, each of a mouse’s cells has a metabolic rate—that is, it burns energy—some fifteen times faster than the cells from a horse. For many years, metabolic rate has been thought to play a major