How long can we live?
David Sinclair, a director of the Paul F. Glenn Center for the Biology of Aging Research at Harvard Medical School, envisions a future in which people receive treatments every decade or so to undo the effects of aging throughout the body.
In 1990, not long after Jean-Marie Robine and Michel Allard began conducting a nationwide study of French centenarians, one of their software programmes spat out an error message. An individual in the study was marked as 115 years old, a number outside the programme’s range of acceptable age values.
They called their collaborators in Arles, where the subject lived, and asked them to double-check the information they had provided, recalls Allard, who was then the director of the IPSEN Foundation, a non-profit research organisation. Perhaps they made a mistake when transcribing her birth date? Maybe this Jeanne Calment was actually born in 1885, not 1875? No, the collaborators said. We’ve seen her birth certificate. The data is correct.
Calment was already well known in her hometown. Over the next few years, as rumours of her longevity spread, she became a celebrity.
Her birthdays, which had been local holidays for a while, inspired national and, eventually, international news stories. Journalists, doctors and scientists began crowding her nursing home room, eager to meet la doyenne de l’humanité. Everyone wanted to know her story.
Calment lived her entire life in the sunburned clay-and-cobble city of Arles in the South of France, where she married a second cousin and moved into a spacious apartment above the store he owned. She never needed to work, instead filling her days with leisurely pursuits: bicycling, painting, roller skating and hunting.
She enjoyed a glass of port, a cigarette and some chocolate nearly every day. In town, she was known for her optimism, good humour and wit.
By age 88, Calment had outlived her parents, husband, only child, son-in-law and grandson. As she approached her 110th birthday, she was still living alone in her apartment.
One day, during a particularly severe winter, the pipes froze. She tried to thaw them with a flame, accidentally igniting the insulating material. Neighbours noticed the smoke and summoned the fire brigade, which rushed her to a hospital.
Following the incident, Calment moved into La Maison du Lac, the nursing home situated on the hospital’s campus, where she would live until her death at age 122 in 1997.
In 1992, as Calment’s fame bloomed, Robine and Allard returned to her file. Clearly, here was someone special — someone who merited a case study. Arles was just an hour’s drive from the village where Robine, a demographer at the French National Institute of Health and Medical Research, lived at the time. He decided to arrange a visit.
At La Maison du Lac, he introduced himself to the medical director, Victor Lèbre, and explained that he wanted to interview Calment. Lèbre replied that it was too late; Calment, he said, was completely deaf. But he agreed to let him meet the grande dame anyway. They walked down a long concrete corridor and into a small and spare room.
“Hello, Madame Calment,” Lèbre said.
“Good morning, doctor,” she answered without hesitation.
Lèbre was so shocked that he grabbed Robine by the arm and rushed him down the corridor back to his office, where he interrogated the nurses about Calment’s hearing. Apparently she could hear quite well at times, but experienced periods of near deafness; Lèbre had most likely mistaken one of those interludes for a permanent condition.
Upon returning to Calment’s room, Robine saw her properly for the first time. She was sitting by the window in an armchair that dwarfed her shrunken frame. Her eyes, milky with cataracts, could distinguish light from dark, but did not focus on any place in particular.
During that first meeting, Robine and Calment mostly exchanged pleasantries. Over the next few years, however, Robine and Allard, in collaboration with several other researchers and archivists, interviewed Calment dozens of times and thoroughly documented her life history, verifying her age and cementing her reputation as the oldest person who ever lived.
Since then, Calment has become something of an emblem of the ongoing quest to answer one of history’s most controversial questions: What exactly is the limit on the human life span?
As medical and social advances mitigate diseases of old age and prolong life, the number of exceptionally long-lived people is increasing sharply. The United Nations estimates that there were about 95,000 centenarians in 1990 and more than 450,000 in 2015. By 2100, there will be 25 million.
Although the proportion of people who live beyond their 110th birthday is far smaller, this once-fabled milestone is also increasingly common in many wealthy nations. The first validated cases of such “supercentenarians” emerged in the 1960s. Since then, their global numbers have multiplied by a factor of at least 10, though no one knows precisely how many there are. In Japan alone, the population of supercentenarians grew to 146 from 22 between 2005 and 2015, a nearly sevenfold increase.
Given these statistics, you might expect that the record for longest life span would be increasing, too. Yet nearly a quarter-century after Calment’s death, no one is known to have matched, let alone surpassed, her 122 years. The closest was an American named Sarah Knauss, who died at age 119, two years after Calment.
The oldest living person is Kane Tanaka, 118, who resides in Fukuoka, Japan. Very few people make it past 115. (A few researchers have even questioned whether Calment really lived as long as she claimed, though most accept her record as legitimate based on the weight of biographical evidence.)
As the global population approaches eight billion, and science discovers increasingly promising ways to slow or reverse aging in the lab, the question of human longevity’s potential limits is more urgent than ever. When their work is examined closely, it’s clear that longevity scientists hold a wide range of nuanced perspectives on the future of humanity.
Historically, however — and somewhat flippantly, according to many researchers — their outlooks have been divided into two broad camps, which some journalists and researchers call the pessimists and the optimists. Those in the first group view life span as a candle wick that can burn for only so long. They generally think that we are rapidly approaching, or have already reached, a ceiling on life span, and that we will not witness anyone older than Calment anytime soon.
In contrast, the optimists see life span as a supremely, maybe even infinitely elastic band. They anticipate considerable gains in life expectancy around the world, increasing numbers of extraordinarily long-lived people — and eventually, supercentenarians who outlive Calment, pushing the record to 125, 150, 200 and beyond.
Though unresolved, the long-running debate has already inspired a much deeper understanding of what defines and constrains life span — and of the interventions that may one day significantly extend it.
The theoretical limits on the length of a human life have vexed scientists and philosophers for thousands of years, but for most of history their discussions were largely based on musings and personal observations. In 1825, however, the British actuary Benjamin Gompertz published a new mathematical model of mortality, which demonstrated that the risk of death increased exponentially with age.
Were that risk to continue accelerating throughout life, people would eventually reach a point at which they had essentially no chance of surviving to the next year. In other words, they would hit an effective limit on life span.
Instead, Gompertz observed that as people entered old age, the risk of death plateaued. “The limit to the possible duration of life is a subject not likely ever to be determined,” he wrote, “even should it exist.” Since then, using new data and more sophisticated mathematics, other scientists around the world have uncovered further evidence of accelerating death rates followed by mortality plateaus not only in humans but also in numerous other species, including rats, mice, shrimp, nematodes, fruit flies and beetles.
In 2016, an especially provocative study in the prestigious research journal strongly implied that the authors had found the limit to the human life span. Jan Vijg, a geneticist at the Albert Einstein College of Medicine, and two colleagues analysed decades’ worth of mortality data from several countries and concluded that although the highest reported age at death in these countries increased rapidly between the 1970s and 1990s, it had failed to rise since then, stagnating at an average of 114.9 years.
Human life span, it seemed, had arrived at its limit. Although some individuals, like Jeanne Calment, might reach staggering ages, they were outliers, not indicators of a continual lengthening of life.
While a few scientists from the more pessimistic tradition applauded the study, many researchers sternly critiqued its methods, in particular the bold generalisation based on what one commentary called a “limited, noisy set of data.” Nearly a dozen rebuttals appeared in and other journals.
James Vaupel, the founding director of the Max Planck Institute for Demographic Research and a staunch critic of the idea that the human life span has reached its limit, called the study a travesty and told the science journalist Hester van Santen that the authors “just shoveled the data into their computer like you’d shovel food into a cow.”
Robine was one of several peer reviewers whom recruited to evaluate the study by Vijg and his co-authors before publication. The first draft did not satisfy Robine’s standards, because it focused only on the United States and relied on data he considered incomplete.
Among other changes, he recommended using the more comprehensive International Database on Longevity, which he and Vaupel developed with colleagues. Van Santen reported in a peer-review post-mortem that, based on the substantial criticism by Robine and one of the other reviewers, Nature initially declined to publish the study.
After Vijg and his co-authors sent a thoroughly revised version, however, Robine conceded that the study was sound enough to publish, though he still disagreed with its conclusions. (Vijg stands by the methodology and conclusions of the study.)
Two years later, in 2018, the equally prestigious journal published a study that completely contradicted the one in .
The demographers Elisabetta Barbi of the University of Rome and Kenneth Wachter of the University of California, Berkeley, along with several colleagues, examined the survival trajectories of nearly 4,000 Italians and concluded that, while the risk of death increased exponentially up to age 80, it then slowed and eventually plateaued.
Someone alive at 105 had about a 50% chance of living to the next year. The same was true at 106, 107, 108 and 109.
Their findings, the authors wrote, “strongly suggest that longevity is continuing to increase over time, and that a limit, if any, has not been reached.”
Many of the disputes over human longevity studies centre on the integrity of different data sets and the varying statistical methods researchers use to analyse them. Where one group of scientists perceives a clear trend, another suspects an illusion. Robine finds the debate exciting and essential.
“I’m not convinced by my colleagues’ suggesting that life is or is not limited,” he told me. “I think the question is still here. We don’t yet know the best kind of analysis or study design to use to tackle this question. The most important thing to do today is to keep collecting the data.”
On their own, however, life-span statistics can tell us only so much. Such data have been available for centuries and have clearly not settled the debate. The number of supercentenarians may still be too small to support unequivocal conclusions about mortality rates in extreme old age.
But in more recent decades, scientists have made considerable progress toward understanding the evolutionary origins of longevity and the biology of aging. Instead of fixating on human demographics, this research considers all species on the planet and tries to derive general principles about duration of life and timing of death.
“I’m a little surprised that anyone today would question whether or not there is a limit,” S. Jay Olshansky, an expert on longevity and a professor in the School of Public Health at the University of Illinois at Chicago, told me. “It doesn’t really matter whether there is a plateau of mortality or not in extreme old age. There are so few people that make it up there, and the risk of death at that point is so high, that most people aren’t going to live much beyond the limits we see today.”
Olshansky, 67, has argued for decades that life span is obviously limited and that the mathematical models of feuding demographers are secondary to the biological realities of aging. He is so thoroughly convinced of his position that he has backed it with an investment that may eventually grow to a sizeable fortune for him or his heirs.
In 2000, Steven Austad, a biologist now at the University of Alabama, Birmingham, told , “The first 150-year-old person is probably alive right now.” When Olshansky disagreed, the two struck up a friendly bet: Each put $150 in an investment fund and signed a contract stipulating that the winner or his descendants would claim the returns in 2150. After the Vijg paper was published, they doubled their contributions.
Olshansky originally invested the funds in gold and later in Tesla. He estimates the value will be well over $1 billion when it’s time to collect. “Oh, I am going to win,” Olshansky said when I asked him how he currently feels about the wager. “Ultimately, biology will determine which one of us is right. That’s why I’m so confident.”
Embedded in the question of the human life span’s limits is a more fundamental enigma: Why do we — why does any organism — get old and die in the first place? As the eminent physicist Richard Feynman put it in a 1964 lecture, “There is nothing in biology yet found that indicates the inevitability of death.”
Some organisms seem to be living proof of this claim. Scientists recently drilled into sediments deep beneath the seafloor and unearthed microbes that had probably survived “in a metabolically active form” for more than 100 million years. Pando, a 106-acre clonal colony of genetically identical aspen trees connected by a single root system in Utah, is thought to have sustained itself for as long as 14,000 years and counting.
A few creatures are so ageless that some scientists regard them as biologically immortal. Hydra, tiny relatives of jellyfish and corals, do not appear to age at all and can regenerate whole new bodies when sliced into pieces.
When injured or threatened, a sexually mature Turritopsis dohrnii, the immortal jellyfish, can revert to its juvenile stage, mature and revert again, potentially forever. Biologically immortal organisms are not impervious to death — they can still perish from predation, lethal injury or infection — but they do not seem to die of their own accord.
Why, then, do so many species expire so dependably? Most longevity researchers agree that aging, the set of physical processes of damage and decay that result in death, is not an adaptive trait shaped by natural selection. Rather, aging is a byproduct of selection’s waning power over the course of an organism’s life.
Selection acts most strongly on genes and traits that help living creatures survive adolescence and reproduce. In many species, the few individuals who make it to old age are practically invisible to natural selection because they are no longer passing on their genes, nor helping raise their relatives’ progeny.
Biologists think life span is largely determined by a species’ anatomy and lifestyle.
Small and highly vulnerable animals tend to reproduce quickly and die not long after, whereas larger animals, and those with sophisticated defences, usually reproduce later in life and live longer overall.
Ground-dwelling birds, for instance, often have shorter life spans than strong-winged, tree-nesting species, which are less susceptible to predators. Naked mole rats, which enjoy the cooperative benefits of tight-knit social groups and the protection of subterranean chambers, live five to 10 times longer than other similarly sized mammals.
Humans have never belonged to the select society of the everlasting. We most likely inherited fairly long life spans from our last common ancestor with chimpanzees, which may have been a large, intelligent, social ape that lived in trees away from ground predators. But we never out-evolved the eventual senescence that is part of being a complex animal with all manner of metabolically costly adaptations and embellishments.
Social advances and improving public health may further increase life expectancy and lift some supercentenarians well beyond Calment’s record. Even the most optimistic longevity scientists admit, however, that at some point these environmentally induced gains will run up against human biology’s limits — unless, that is, we fundamentally alter our biology.
Many scientists who study aging think that biomedical breakthroughs are the only way to substantially increase the human life span, but some doubt that anyone alive today will witness such radical interventions; a few doubt they are even possible. In any case, longevity scientists agree, significantly elongating life without sustaining well-being is pointless, and enhancing vitality in old age is valuable regardless of gains in maximum life span.
One of the many obstacles to these goals is the overwhelming complexity of aging in mammals and other vertebrates. Researchers have achieved astonishing results by tweaking the genome of the roundworm C. elegans, extending its life span nearly 10 times — the equivalent of a person’s living 1,000 years.
Although scientists have used caloric restriction, genetic engineering and various drugs to stretch life span in more complex species, including fish, rodents and monkeys, the gains have never been as sharp as in roundworms, and the precise mechanisms underlying these changes remain unclear.
In a study published in in December 2020, David Sinclair, a director of the Paul F. Glenn Center for the Biology of Aging Research at Harvard Medical School, along with colleagues, partly restored vision in middle-aged and ailing mice by reprogramming their gene expression. The researchers injected the mice’s eyes with a benign virus carrying genes that revert mature cells to a more supple, stem-cell-like state, which allowed their neurons to regenerate — an ability that mammals usually lose after infancy.
“Aging is far more reversible than we thought,” Sinclair told me. “Cells can clean themselves up, they can get rid of old proteins, they can rejuvenate, if you turn on the youthful genes through this reset process.”
Known for his boyish features and sanguine predictions, Sinclair, 51, and several of his family members (including his dogs) follow versions of his life-prolonging regimen, which has, over the years, included regular exercise, sauna steams and ice baths, a two-meal-a-day mostly vegetarian diet, the diabetes drug metformin (which is purported to have anti-aging properties) and several vitamins and supplements, like the once-hyped but ultimately disappointing red-wine miracle molecule resveratrol.
Sinclair has also founded at least 12 biotech companies and serves on the boards of several more, one of which is already pursuing human clinical trials of a gene therapy based on his recent study. In a talk at Google, he envisioned a future in which people receive similar treatments every decade or so to undo the effects of aging throughout the body.
“We don’t know how many times you can reset,” he said. “It might be three, it might be 3,000. And if you can reset your body 3,000 times, then things get really interesting. I don’t know if any of you want to live for 1,000 years, but I also don’t know if it’s going to be possible, but these are the questions we have to start thinking about. Because it’s not a question of if — it’s now a question of when.”
- New York Times
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