Why aren't the oldest living people getting any older?
Will we ever live to 150?
Last month, a 114-year-old former schoolteacher from Georgia named Besse Cooper became the world's oldest living person. Her predecessor, Brazil's Maria Gomes Valentim, was 114 when she died. So was the oldest living person before her, and the one before her. In fact, eight of the last nine "world's oldest" titleholders were 114 when they achieved the distinction. Here's the morbid part: All but two were still 114 when they passed it on. Those two? They died at 115.
The celebration surrounding Cooper when she assumed the title, then, might as well have been accompanied by condolences. If historical trends hold, she will likely be dead within a year.
It's no surprise that it's hard to stay the "world's oldest" for very long. These people are, after all, really old. What's surprising is just how consistent the numbers have been. Just seven people whose ages could be fully verified by the Gerontology Research Group have ever made it past 115. Only two of those seven lived to see the 21st century. The longest-living person ever, a French woman named Jeanne Calment, died at age 122 in August 1997; no one since 2000 has come within five years of matching her longevity.
The inventor Ray Kurzweil, famous for bold predictions that occasionally come true, estimated in 2005 that, within 20 years, advances in medical technology would enable humans to extend their lifespans indefinitely. With six years gone and 14 to go, his prophecy doesn't seem that much closer to coming true. What happened to modern medicine giving us longer lives? Why aren't we getting any older?
We are living longer - at least, some of us are. Life expectancies in most countries not ravaged by AIDS have been rising gradually for decades, and the average American today can expect to live 79 years -four years longer than the average in 1990. In many developed countries, the superold are among the fastest-growing demographics. (There is evidence that this progress may be grinding to a halt among some demographics, however.) But raising the upper bounds of the human lifespan is turning out to be trickier than increasing the average person's life expectancy. This may be a case where, as with flying cars, a popular vision of technological progress runs afoul of reality's constraints.
In the past few years, the global count of supercentenarians - people 110 and older - has leveled off at about 80. And the maximum age hasn't budged. Robert Young, senior gerontology consultant for the Guinness Book of World Records, says, "The more people are turning 110, the more people are dying at 110."
Young calls this the "rectangularization of the mortality curve." To illustrate it, he points to Japan, which in 1990 had 3,000 people aged 100 and over, with the oldest being 114. Twenty years later, Japan has an estimated 44,000 people over the age of 100 - and the oldest is still 114. For reasons that aren't entirely clear, Young says, the odds of a person dying in any given year between the ages of 110 and 113 appear to be about one in two. But by age 114, the chances jump to more like two in three.
It's still possible that the barrier will eventually go the way of the four-minute mile. Steve Austad, a former lion tamer who is now a professor at the University of Texas Health Science Center, argues the apparent spike in mortality at age 114 is merely a statistical artifact. Today's oldest humans, he's reminds us, grew up without the benefit of 20th-century advances in nutrition and medicine. In 2000, he bet fellow gerontologist S. Jay Olshansky $500 million that someone born that year, somewhere in the world, would live to be 150. Olshansky, an Illinois at Chicago professor who wrote about the paradox of longevity for Slate last fall, doesn't expect to be around in 2150 to collect his winnings. Even a cure for cancer or heart disease would do little to extend the maximum length of human life, he argues, because there are simply too many risk factors that pile up by the time a person is 115 years old. He believes supercentenarians owe their longevity more to freakish genes than perfect health; the 122-year-old Calment smoked cigarettes for 96 years. Olshansky and Austad agree on one point: A technological breakthrough, perhaps in the realm of genetics, that slows the aging process could send life spans surging upward.
Is such a discovery imminent? At this point, the question is little more than a Rorschach. Young, the Guinness World Records consultant, compares the quest for superlongevity to the efforts of alchemists in the Middle Ages to turn lead into gold. They were right to think it was possible, but wrong to imagine they had any idea where to begin: Scientists finally succeeded in transmuting elements in the 20th century only after first unlocking nuclear physics. By that time, alchemy was largely irrelevant; the real trick was splitting uranium atoms.
The same may be true of enabling humans to live to 150. Age, it's worth remembering, is more than just a number. Young, who has spent time with dozens of supercentenarians, says even the hardiest humans turn frail by 110. As for Besse Cooper, the new world titleholder, Young reports that she can still talk, though her eyesight is failing. "As a quality-of-life issue, I think she could handle another year. I've seen some that, bless their hearts, probably shouldn't be here anymore."
Aging
BIOLOGISTS have made a lot of progress in understanding ageing. They have not, however, been able to do much about slowing it down. Particular versions of certain genes have been shown to prolong life, but that is no help to those who do not have them. A piece of work reported in Nature Magazine by Darren Baker of the Mayo Clinic, in Minnesota, though, describes an extraordinary result that points to a way the process might be ameliorated. Dr Baker has shown - in mice, at least - that ageing body cells not only suffer themselves, but also have adverse effects on otherwise healthy cells around them. More significantly, he has shown that if such ageing cells are selectively destroyed, these adverse effects go away.
The story starts with an observation, made a few years ago, that senescent cells often produce a molecule called P16INK4A. Most body cells have an upper limit on the number of times they can divide - and thus multiply in number. P16INK4A is part of the control mechanism that brings cell division to a halt when this limit is reached.
The Hayflick limit, as the upper bound is known (after Leonard Hayflick, the biologist who discovered it), is believed to be an anticancer mechanism. It provides a backstop that prevents a runaway cell line from reproducing indefinitely, and thus becoming a tumour. The limit varies from species to species - in humans, it is about 60 divisions - and its size is correlated with the lifespan of the animal concerned. Hayflick-limited cells thus accumulate as an animal ages, and many biologists believe they are one of the things which control maximum lifespan. Dr Baker's experiment suggests this is correct.
Age shall not weary them
Dr Baker genetically engineered a group of mice that were already quite unusual. They had a condition called progeria, meaning that they aged much more rapidly than normal mice. (A few unfortunate humans suffer from a similar condition.) The extra tweak he added to the DNA of these mice was a way of killing cells that produce P16INK4A. He did this by inserting into the animals' DNA, near the gene for P16INK4A, a second gene that was, because of this proximity, controlled by the same genetic switch. This second gene, activated whenever the gene for P16INK4A was active, produced a protein that was harmless in itself, but which could be made deadly by the presence of a particular drug. Giving a mouse this drug, then, would kill cells which had reached their Hayflick limits while leaving other cells untouched. Dr Baker raised his mice, administered the drug, and watched.
The results were spectacular. Mice given the drug every three days from birth suffered far less age-related body-wasting than those which were not. They lost less fatty tissue. Their muscles remained plump (and effective, too, according to treadmill tests). And they did not suffer cataracts of the eye. They did, though, continue to experience age-related problems in tissues that do not produce P16INK4A as they get old. In particular, their hearts and blood vessels aged normally (or, rather, what passes for normally in mice with progeria). For that reason, since heart failure is the main cause of death in such mice, their lifespans were not extended.
The drug, Dr Baker found, produced some benefit even if it was administered to a mouse only later in life. Though it could not clear cataracts that had already formed, it partly reversed muscle-wasting and fatty-tissue loss. Such mice were thus healthier than their untreated confreres.
Analysis of tissue from mice killed during the course of the experiment showed that the drug was having its intended effect. Cells producing P16INK4A were killed and cleared away as they appeared. Dr Baker's results therefore support the previously untested hypothesis that not only do cells which are at the Hayflick limit stop working well themselves, they also have malign effects (presumably through chemicals they secrete) on their otherwise healthy neighbours.
Regardless of the biochemical details, the most intriguing thing Dr Baker's result provides is a new way of thinking about how to slow the process of ageing - and one that works with the grain of nature, rather than against it. Existing lines of inquiry into prolonging lifespan are based either on removing the Hayflick limit, which would have all sorts of untoward consequences, or suppressing production of the oxidative chemicals that are believed to cause much of the cellular damage which is bracketed together and labelled as senescence. But these chemicals are a by-product of the metabolic activity that powers the body. If 4 billion years of natural selection have not dealt with them it suggests that suppressing them may have worse consequences than not suppressing them.
By contrast, actually eliminating senescent cells may be a logical extension of the process of shutting them down (they certainly cannot cause cancer if they are dead), and thus may not have adverse consequences. It is not an elixir of life, for eventually the body will run out of cells, as more and more of them reach their Hayflick limits. But it could be a way of providing a healthier and more robust old age than people currently enjoy.
Genetically engineering people in the way that Dr Baker engineered his mice is obviously out of the question for the foreseeable future. But if some other means of clearing cells rich in P16INK4A from the body could be found, it might have the desired effect. The wasting and weakening of the tissues that accompanies senescence would be a thing of the past, and old age could then truly become ripe.