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.
1990年，让—马里·罗比内(Jean-Marie Robine)和米歇尔·阿拉尔(Michel Allard)开始进行一项对法国百岁老人的全国性研究不久后，他们计算机程序中之一突然吐出了一条错误信息。一名研究对象的标记年龄是115岁，这个数字超出了该项目设定的年龄值范围。当时是非营利研究机构IPSEN基金会负责人的阿拉尔回忆说，他们给在阿尔勒（该究对象居住的地方）的合作者打了电话，请其对提供的信息进行复查。也许他们输入的出生日期有误？也许这个叫让娜·卡尔芒(Jeanne Calment)的人是1885年出生的，而不是1875年？没出错，合作者说。我们看过她的出生证明。
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.
卡尔芒88岁时变成孤身一人，她的父母、丈夫、独生女、女婿和外孙都已先她而去。快到110岁生日时，她仍独自住在自己珍爱的公寓里。在一个特别寒冷的冬季，有一天，水管结了冰。她试图用火焰将管道里的冰融化，却不小心点燃了隔热材料。邻居们看到浓烟后，叫来了消防队，消防队迅速将她送到医院。这件事后，卡尔芒搬进了位于医院园区的La Maison du Lac 养老院，一直住在那里，直到1997年以122岁的高龄去世。
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.
The day they met, Calment was sitting by the window in her room, 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. She could hear quite well at times, but experienced periods of near deafness. 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.
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. Longevity scientists hold a wide range of nuanced perspectives on the future of humanity. Historically — 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. The pessimists view life span as a candle wick that can burn for only so long; the optimists see life span as a supremely, maybe even infinitely, elastic band.
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. Instead, Gompertz observed that as people entered old age, the risk of death plateaued. 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.
人类寿命的理论极限问题已困扰科学家和哲学家几千年了，但在历史上的大部分时间里，他们的讨论主要建立在冥想和个体观察的基础上。但英国精算师本杰明·冈珀茨(Benjamin Gompertz) 1825年发表了死亡率的一个新数学模型，模型显示，死亡风险以指数关系随年龄增长。如果死亡风险在一生中持续加速的话，人最终会达到基本上不可能活到下一年的寿命点。但冈珀茨的观察反而是，随着人进入老年，死亡风险却保持在稳定水平。他之后，世界各地的其他科学家使用新的数据和更复杂的数学模型，找到了死亡率先是加速上升、然后保持稳定的进一步证据，不仅在人类中如此，在许多其他物种中也是如此。
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. 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. Nearly a dozen rebuttals appeared in Nature and other journals.
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.”
在两年后的2018年，同样享有盛誉的《科学》(Science)杂志发表了一项与《自然》发表的研究完全矛盾的研究。人口统计学家、罗马大学的伊丽莎贝塔·巴尔比(Elisabetta Barbi)和加州大学伯克利分校的肯尼斯·瓦赫特(Kenneth Wachter)以及几位同事，对近4000名意大利人的生存记录进行了研究，得出结论，尽管死亡风险在80岁之前呈指数增长，但之后的增长速度会放缓，并最终趋于稳定。活到105岁的人有50%的可能活到下一年。活到106、107、108和109岁的人也同样。文章作者写道，他们的研究结果“强烈暗示，人类寿命随着时间继续增长，如果有极限的话，还没有达到。”
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 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.
然而在最近，研究者测试了一些格外新颖的技术，以逆转和推延衰老的某些方面，取得了初步但有希望的成果。明尼苏达州罗彻斯特市梅奥诊所(Mayo Clinic)研究衰老的专家詹姆斯·柯克兰(James Kirkland)已经和同事们证明，特定的药物混合可以清除老年鼠的衰老细胞，让它们多得到一个多月的健康生活。他们的研究已经启发了许多人体临床试验。在加州大学伯克利分校(University of California, Berkeley)，生物工程师夫妇伊琳娜(Irina)和迈克尔·康博伊(Michael Conboy)正在研究如何过滤或稀释啮齿动物的老化血液，以去除抑制愈合的分子，从而反过来刺激细胞再生以及再生化合物的形成。
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.”
在2020年12月发表于《自然》的一项研究中，哈佛医学院(Harvard Medical School)保罗·F·格伦衰老生物学研究中心(Paul F. Glenn Center for the Biology of Aging Research)主任戴维·辛克莱尔(David Sinclair)与其同事通过重新编写基因表达，部分恢复了中年和患病鼠的视力。研究者为老鼠眼睛注射了一种良性病毒，这种病毒携带的基因可以将成熟细胞恢复到更柔软的干细胞样状态，从而使它们的神经元能够再生——哺乳动物通常在婴儿期后就失去了这种能力。“衰老的可逆远超我们想象，”辛克莱尔告诉我。“只要你通过这个重置过程打开年轻的基因，细胞就可以自我清理，可以清除陈旧蛋白质，可以恢复活力。”
Known for his boyish features and sanguine predictions, Sinclair, 51, 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.”
Longevity scientists who favor the idea of living for centuries or longer tend to speak effusively of prosperity and possibility. 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. 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?”
一些专家还说，大量留在人世的超级老年人还将扼杀新生代的成长，阻碍社会进步。“让老一代人消失的进化过程是有其智慧的，”埃默里大学(Emory University)伦理中心主任保罗·鲁特·沃尔普(Paul Root Wolpe)在一次关于延长寿命的公开辩论中表示。“如果经历一战和二战的一代人，或者是经历内战的一代人还活着，你真的认为这个国家会有民权吗？会有同性婚姻吗？”
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, during an especially hot summer, Calment died alone in her nursing-home room from unknown causes.
“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.