Ferris Jabr, “How Long Can We Live?

In 1990, not long after Jean-Marie Robine and Michel Allard began conducting a nationwide
study of French centenarians, one of their software programs spat out an error message. An
individual in the study was marked as 115 years old, a number outside the program’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 nonprofit research organization. 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 rumors 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 humor and wit. (“I’ve never
had but one wrinkle,” she once said, “and I’m sitting on it.”)

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 cherished apartment. One
day, during a particularly severe winter, the pipes froze. She tried to thaw them with a flame,
accidentally igniting the insulating material. Neighbors 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. Her plain gray clothes appeared to be several
decades old.

During that first meeting, Robine and Calment mostly exchanged pleasantries and idle chatter.
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 Nature 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 analyzed 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 generalization based on what one
commentary called a “limited, noisy set of data.” Nearly a dozen rebuttals appeared in Nature
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 remembers the furor well. He was one of several peer reviewers whom Nature 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 Nature 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 Science published a study that
completely contradicted the one in Nature. 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 percent 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 center on the integrity of different data sets
and the varying statistical methods researchers use to analyze 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 likes to make an analogy to athletics: “Could someone run a two-minute mile? No. The
human body is incapable of moving that fast based on anatomical limitations. The same thing
applies to human longevity.”
He is so thoroughly convinced of his position that he has backed it with an investment that may
eventually grow to a sizable fortune for him or his heirs. In 2000, Steven Austad, a biologist now
at the University of Alabama, Birmingham, told Scientific American, “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. Theoretically, any organism with a continual supply of energy, a sufficient capacity for
self-maintenance and repair and the good fortune to evade all environmental hazards could
survive until the end of the universe.

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.

As the British biologist Peter Medawar observed in the 1950s, harmful genetic mutations that are
not expressed until late in life could accumulate across generations because selection is too weak
to remove them, eventually resulting in specieswide aging. The American biologist George C.
Williams elaborated on Medawar’s ideas, adding that some genes may be beneficial in youth but
detrimental later on, when selection would overlook their disadvantages. Similarly, in the 1970s,
the British biologist Thomas Kirkwood proposed that aging was partly due to an evolutionary
trade-off between growth and reproduction on the one hand and day-to-day maintenance on the
other. Devoting resources to maintenance is advantageous only if an organism is likely to
continue surviving and reproducing. For many organisms, external threats are too great and
numerous to endure for very long, so there is not much evolutionary pressure to preserve their
bodies in old age, resulting in their deterioration.

But that still leaves the question of why there is such huge variation in life span among species.
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 defenses, 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.

A few species, like stalwart clonal trees with resilient root systems, are so well protected against
environmental hazards that they don’t have to prioritize early growth and reproduction over
long-term maintenance, allowing them to live an extraordinarily long time. Others, like the
immortal jellyfish and hydra, are potentially indefinite, because they have retained primordial
powers of rejuvenation that have been relegated to pockets of stem cells in most adult vertebrates.

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.

As the years pass, our chromosomes contract and fracture, genes turn on and off haphazardly,
mitochondria break down, proteins unravel or clump together, reserves of regenerative stem cells
dwindle, bodily cells stop dividing, bones thin, muscles shrivel, neurons wither, organs become
sluggish and dysfunctional, the immune system weakens and self-repair mechanisms fail. There is
no programmed death clock ticking away inside us — no precise expiration date hard-wired into
our species — but, eventually, the human body just can’t keep going.

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.

More recently, however, researchers have tested particularly innovative techniques for reversing
and postponing some aspects of aging, with tentative but promising results. James Kirkland, an
expert on aging at the Mayo Clinic in Rochester, Minn., has demonstrated with colleagues that
certain drug cocktails purge old mice of senescent cells, granting them more than a month of
additional healthy living. Their research has already inspired numerous human clinical trials.

At the same time, at the University of California, Berkeley, the married bioengineers Irina and
Michael Conboy are investigating ways to filter or dilute aged blood in rodents to remove
molecules that inhibit healing, which in turn stimulates cellular regeneration and the production
of revitalizing compounds.

In a study published in Nature 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 Nature 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.”

Longevity scientists who favor the idea of living for centuries or longer tend to speak effusively of
prosperity and possibility. As they see it, sustaining life and promoting health are intrinsically
good and, therefore, so are any medical interventions that accomplish this. Biomedically
extended longevity would not only revolutionize general well-being by minimizing or preventing
diseases of aging, they say, it would also vastly enrich human experience. It would mean the
chance for several fulfilling and diverse careers; the freedom to explore much more of the world;
the joy of playing with your great-great-great-grandchildren; the satisfaction of actually sitting in
the shade of the tree you planted so long ago. Imagine, some say, how wise our future elders
could be. Imagine what the world’s most brilliant minds could accomplish with all that time.

In sharp contrast, other experts argue that extending life span, even in the name of health, is a
doomed pursuit. Perhaps the most common concern is the potential for overpopulation,
especially considering humanity’s long history of hoarding and squandering resources and the
tremendous socioeconomic inequalities that already divide a world of nearly eight billion. There
are still dozens of countries where life expectancy is below 65, primarily because of problems like
poverty, famine, limited education, disempowerment of women, poor public health and diseases
like malaria and H.I.V./AIDS, which novel and expensive life-extending treatments will do
nothing to solve.

Lingering multitudes of superseniors, some experts add, would stifle new generations and impede
social progress. “There is a wisdom to the evolutionary process of letting the older generation
disappear,” said Paul Root Wolpe, the director of the Center for Ethics at Emory University,
during one public debate on life extension. “If the World War I generation and World War II
generation and perhaps, you know, the Civil War generation were still alive, do you really think
that we would have civil rights in this country? Gay marriage?”

In her final years at La Maison du Lac, the once-athletic Jeanne Calment was essentially
immobile, confined to her bed and wheelchair. Her hearing continued to decline, she was
virtually blind and she had trouble speaking. At times, it was not clear that she was fully aware of
her surroundings.

By some accounts, those in charge of Calment’s care failed to shield her from undue commotion
and questionable interactions as journalists, tourists and spectators bustled in and out of her
room. Following the release of an investigative documentary, the hospital director barred all
visitors. The last time Robine saw her was shortly after her 120th birthday. About two years
later, in the midst of an especially hot summer, Jeanne Calment died alone in her nursing-home
room from unknown causes and was quickly buried. Only a few people were permitted to attend
her funeral. Robine and Allard were not among them. Neither was Calment’s family: All her
close relatives had been dead for more than three decades.

“Today, more people are surviving the major diseases of old age and entering a new phase of
their life in which they become very weak,” Robine said. “We still don’t know how to avoid
frailty.”

Perhaps the most unpredictable consequence of uncoupling life span from our inherited biology
is how it would alter our future psychology. All of human culture evolved with the understanding
that earthly life is finite and, in the grand scheme, relatively brief. If we are one day born
knowing that we can reasonably expect to live 200 years or longer, will our minds easily
accommodate this unparalleled scope of life? Or is our neural architecture, which evolved amid
the perils of the Pleistocene, inherently unsuited for such vast horizons?

Scientists, philosophers and writers have long feared that a surfeit of time would exhaust all
meaningful experience, culminating in debilitating levels of melancholy and listlessness. Maybe
the desire for all those extra years masks a deeper longing for something unattainable: not for a
life that is simply longer, but for one that is long enough to feel utterly perfect and complete.

In Jorge Luis Borges’s short story “The Immortal,” a Roman military officer stumbles upon a
“secret river that purifies men of death.” After drinking from it and spending eons in deep
thought, he realizes that death imbues life with value, whereas, for immortals, “Nothing can
occur but once, nothing is preciously in peril of being lost.” Determined to find the antidote to
everlasting life, he wanders the planet for nearly a millennium. One day, he drinks from a spring
of clear water on the Eritrean coast and shortly thereafter scratches the back of his hand on a
thorny tree. Startled by an unfamiliar twinge of pain, he searches for a sign of injury. As a drop
of blood slowly pools on his skin — proof of his restored mortality — he simply watches,
“incredulous, speechless, and in joy.”

Ferris Jabr is a contributing writer for the magazine. His January 2019 cover story on the
evolution of beauty is featured in the latest edition of The Best American Science and Nature
Writing. Maurizio Cattelan is an Italian artist whose work has been the subject of numerous
solo exhibitions, including shows at the Guggenheim Museum in New York and the Pompidou
Center in Paris. Pierpaolo Ferrari is an Italian photographer and, along with Cattelan, is a co-
founder of the magazine Toiletpaper, known for its surreal and humorous imagery.