Everywhere on earth, people are living longer than ever before—on average. The fastest-growing age group is centenarians, although living to a hundred years of age is still a rare accomplishment. Fewer than one person in a thousand lives that long, even in Japan, today's longest-lived country.
Rare though they may be, the number of centenarians alive today has almost quadrupled since Jeanne Calment's death in 1997. But for all this increase, some twenty-four years after her death, no one has approached Jeanne Calment's longevity record. For that matter, no one has surpassed the 119-year longevity of Sarah Knauss. It is also difficult to ignore the fact that the rate of life expectancy increase in the world's longest-lived countries has slowed appreciably, even before we were blasted by COVID-19. Life expectancy in the United States, for instance, has not increased since 2015.
If you want to start a brawl at a demography convention, bring up the subject of a "limit" to human life. Is there a limit to life expectancy? Is there a longevity limit that no human will ever surpass? Either question will probably do for one demographer or another to throw the first punch.
More and more people, living longer and longer and pushing up against a limit of human life, could require more and more medical help and could live more and more years in pain—demented and disabled.
In 1980, Stanford physician James Fries made a strange, somewhat optimistic, somewhat pessimistic prediction. He claimed — and still claims, in fact — that the limit of life expectancy is about eighty-five years. That's the pessimistic part of his prediction. The optimistic part is that he also predicted that science will continue to find ways to keep us healthy longer, so that more and more of those eighty-five years will be spent in good health. The period of ill health that many suffer will be compressed into a smaller and smaller slice of time. The alternative is frightening. More and more people, living longer and longer and pushing up against a limit of human life, could require more and more medical help and could live more and more years in pain—demented and disabled. Some people might say that we are reaching toward that dystopian future today as healthcare systems worldwide groan under the weight of care for the elderly.
A decade after Fries made this prediction, it was echoed by a group of professional demographers, most notably S. Jay Olshansky from the University of Illinois Chicago, who has been particularly vocal on the issue. Olshansky also weighed in on the length of maximum life. He offered then and still thinks that no one is likely to surpass Jeanne Calment's longevity record by more than a few years — ever. Other demographers have been equally vociferous about their opinion that human life has no limit. They think that life expectancy will keep rising for the foreseeable future and that maximum longevity records will be broken again and again. One group has predicted that people born after the year 2000, which includes all the students I teach today, can expect to live a century or more. For what it's worth, some forty years after Fries's prediction, Japan now has a life expectancy of 84½ years. The "limit" people can smirk about this. The no-limits crowd would be quick point out that Japanese life expectancy is being dragged down by those wimpy men. Japanese women have already surpassed the Fries limit. They can now expect to live 87½ years. It was mainly due to my appreciation for the lessons nature could teach us about living healthy and living long that Olshansky and I made our $1 billion wager, which I'll describe shortly.
The workhorse of medical research continues to be the laboratory mouse — one of the shortest-lived and most cancer-prone mammals known.
Recall that nature — in the guise of certain animals such as birds, bats, and mole-rats — has repeatedly discovered how to deal with damaging free radicals much better than humans can. Other species (like elephants and whales) have developed dramatically better cancer resistance than humans. Still others, such as my beloved quahogs, have evolved ways to keep muscles strong and hearts beating for centuries. At some point, I am confident, the full armamentarium of the biomedical research enterprise will be deployed to study and eventually understand these lessons nature has to teach us about preserving and prolonging health.
The biochemist Leslie Orgel, who is famous for his research on the origin of life, was fond of pointing out something that should be obvious to all readers of this book by now. In fact, he pointed it out so often that it has become known as "Orgel's second rule" — to wit, evolution is cleverer than you are. What Orgel meant by his second rule, of course, was that evolution, with several billion years and billions of species with which to tinker, will have discovered solutions to problems that humans might never dream of. In the context of prolonging our health, this means that nature will have discovered many ways of combating the inherently destructive processes of life, such as free-radical damage and protein misfolding. Given that such a well-respected scientist pointed out such an obvious truth decades ago, I am somewhat astonished that the biomedical research community has stuck largely with studying animals that are so demonstrably failures at combating these processes. The workhorse of medical research continues to be the laboratory mouse — one of the shortest-lived and most cancer-prone mammals known. In a certain sense, I understand why. So much work has gone into developing tools for instructive intervening in mouse biology that we can do more sophisticated experiments with the mouse than any other mammal. We can deliberately turn individual genes on or off in any part of the mouse body at any time during a mouse's life. We can insert genes from humans, whales, bats, or other species into the mouse and turn them on and off when and where we wish. But genes do not operate in isolation. A whale gene in a mouse may do little more than caricature its role in its hometown, so to speak. Genes' activities must be coordinated like the instruments in an orchestra if you want them to produce beautiful music. Introducing a car horn into an orchestra is not likely to improve its music, no matter how useful the car horn may be in its native environment.
Because of the mouse's short life, we can also determine quickly whether a particular gene variant or new drug will preserve health or life in a mouse. In fact, researchers focusing on the biology of aging have already discovered about a dozen drugs that keep mice healthy and alive longer. Some of these drugs are in early human trials as I write. I purposely am not mentioning the names of any of them because some people are so desperate to live longer they might start taking them before we know for sure whether they are safe, much less effective, for people. What works in mice does not necessarily work in humans.
Medical research is as inherently tradition-bound and conservative as any ecclesiastical hierarchy.
Certainly, some of these drugs may represent longevity breakthroughs. Time will tell. But remember, mice are losers in the game of healthy longevity. An exercise designed to improve the gait of the lame may be unlikely enhance the speed of an already accomplished sprinter. Mice are lame, but humans are already accomplished sprinters. So a drug that allows a mouse to live three rather than two years (or a fruit fly three rather than two months) may be unlikely to extend human health. Human biology may have already solved whatever problems limit a mouse's life. Don't forget, we are already the longest-lived terrestrial mammal. A mouse could learn a great deal about improving and extending its health from studying us. From this perspective, it is hardly surprising that only about one in ten cancer therapies effective in mice has turned out to also be effective in people. We are certainly grateful for the one in ten of those therapies, but might there be a more evolutionarily sensible approach to prolong health? For Alzheimer's disease, none of the over three hundred mouse successes has succeeded in people.
Medical research is as inherently tradition-bound and conservative as any ecclesiastical hierarchy. Funds for research are distributed according to the opinions of scientists who are exquisitely well trained in spotting flaws and detecting uncertainties in traditional experimental paradigms. I ought to know, as I have served on many, many such committees, and I plead guilty to having weighed in on such flaws and uncertainties as I found. There is nothing wrong with such scientific conservatism. It prevents money being wasted on hopelessly wrong-headed research.
But there is also a role for the scientifically adventurous and for out-of-normal-bounds research—for the wild and crazy idea that just might turn out to be true and, if so, then revolutionary. An acquaintance of mine, who also happens to be a Nobel Prize winner, likes to recount with glee how the work that won him his Nobel Prize was the only part of his research proposal that was rejected by a governmental review group.
But I think this hidebound approach to health research is changing. The bestiary of acceptable species on which respectable researchers can experiment is expanding. Naked mole-rats and blind mole-rats are now safely within the research bestiary. That progress may be due to another kind of limit — the limit of what we can learn from studying short-lived, cancer-prone laboratory species. As more and more people realize that nature provides us many examples of animals that combat fundamental aging processes more successfully than humans, there will be pressure to see what we can learn from those species. Some of that pressure may come from the private sector, where some very wealthy people appear to have a personal interest in remaining healthy longer. If you pay attention to headlines, this already seems to be happening.
We are not likely to have laboratory colonies of Greenland sharks, bow-head whales, rough-eyed rockfish, or even Brandt's bats any time soon. The good news is that while we may not have whales in the lab, we can have whales in a dish. That is, we can grow and study whale cells grown in the lab in exquisite detail today. The 2012 Nobel Prize in physiology or medicine was won by Shinya Yamanaka for discovering how to transform skin, liver, blood, or virtually any cell type into stem cells. Stem cells in a dish can in turn be transformed back into heart cells, muscle cells, or brain cells or even turned into miniature organs. An obvious use of the Yamanaka technology is to develop it to grow replacement parts for aging humans from their own cells. We are not far from being able to use this technology to cure certain diseases such as diabetes and Parkinson's disease. But a less obvious use of Yamanaka technology is to study how bird or bat or whale or shark brain or muscle cells deal with damaging free radicals and avoid turning cancerous or how quahog cells avoid misfolding their proteins for centuries.
Methuselah's Zoo, I believe, holds the key to prolonging human health. It may seem like a radical idea but perhaps a radical idea whose time has come. Let's all agree to acknowledge that evolution is cleverer than you are. Are you listening, Silicon Valley zillionaires?
It was this sort of thinking that led to my $1 billion wager.
It was 2001. I found myself sitting in a small conference room on the UCLA campus with perhaps a dozen scientists and a reporter from the New York Times. We had come together to discuss the future of human health. The reporter asked a question: when will we see the first 150-year-old human? We shifted uncomfortably in our seats. No one wanted to go out on a limb— except me. I blurted out, "I think that person is already alive." As I think back on that moment, it seems like that was exactly the right question to ask. And, amazingly, I think I gave exactly the right answer.
No one, I suspect, thinks that we will ever see a 150-year-old human, someone nearly thirty years older than Jeanne Calment, just because we have gotten better and better at diagnosing and treating individual diseases like cancer, stroke, and dementia. I certainly don't think that. It will happen only if we learn to treat aging itself as if it were a disease and delay or eliminate all those diseases simultaneously.
Jay Olshansky, premier public skeptic of exceptional longevity, whom I already knew and respected, read an account of this conference and phoned me to disagree. How strongly did I believe that, he asked. Would I like to make a friendly wager?
We didn't actually put up half a billion dollars each. Neither of our university salaries were quite up to that. What we did decide to do was put up $150 apiece. It had a nice symmetry. $150 each for 150 years to see if a 150-year-old human was alive. Olshansky did some quick back-of-the-envelope calculations. At the historic growth rate of the US stock market, our $300 could in 150 years turn into about $500 million. A dozen years later, when no one had still approached the age of Jeanne Calment, a reporter asked us once again whether we still felt confident that we would win our bet. We both did. To prove it, we doubled its size, each putting another $150 into the pot. Now we could safely claim that our wager was for a cool $1 billion. Even better, Olshansky had been actively investing our money, and now some twenty years after we made the wager, our pot had grown at considerably faster than the historical rate of the US stock market.
So what exactly was the wager? If by the year 2150 there exists or has ever existed a single, thoroughly documented 150-year-old and if that 150-year-old is mentally competent enough to hold a simple conversation, then my descendants — or in the best of all scenarios, I myself—will get the accumulated wealth. If not, then Olshansky's descendants will inherit the money.
I keep documentation of the wager in a safe place. My daughters have been informed of their—or their sons' and daughters'—future wealth. In many public debates and private conversations, Olshansky and I have discovered that we agree on many things. We agree that traditional medical research will not get us to the 150-year-old human. We agree that the only way to accomplish that is to find ways to treat aging itself as if it were a disease. A relatively small group of scientists, including yours truly, is working on exactly this in a new research specialty we call geroscience. Olshansky and I disagree only on how rapidly the big breakthroughs in treating aging will occur. Most of my geroscientist colleagues are sticking with the tried and true laboratory animals. But a few are now branching out. Many species with exceptional resistance to aging now have now had their genomes sequenced, and their cells are safely tucked away in laboratories, where researchers labor to learn their secrets. On the day that we can rely on staying healthy for ninety or a hundred years and somewhere someone is 150 years old or older, then we will have the creatures in Methuselah's Zoo to thank.
Adapted from "Methuselah's Zoo: What Nature Can Teach Us About Living Longer, Healthier Lives" by Steven N. Austad, published by The MIT Press.
