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The Human Lifespan Has a Natural Limit. Scientists Might Know How to Break It

In the future, aging will be treated not as a natural process, but as a disease.

by Kate Lunau
Oct 5 2016, 5:00pm

Image: Shutterstock

We all want to live forever, whether we'll admit it or not. How else to explain the restrictive diets, the wrinkle creams, or the more bizarre therapies and treatments—cryogenic freezing comes to mind—that people seek out to stay young?

Life expectancy has increased in leaps and bounds just in the last 100 years. At the turn of the last century, we humans could expect a mere 45 to 50 years on this planet. Today, it's more like 75 or 80 in many parts of the world. Given the speed of progress, and the promise of future technologies, it seems realistic to expect that this trend will continue. The diseases that kill most of us today, like heart disease, cancer, and neurodegenerative disease, will be stamped out. Our natural lifespan will stretch to 100 years and beyond.

Here's the problem, though: It seems that nature has put a cap on how long humans can live, and we might have already reached it. Human lifespan has a natural limit that can't be surpassed, suggests a new analysis of global demographic data published in Nature. It notes that the world's oldest known person is Jeanne Calment, a French woman who died at the ripe old age of 122 years. That was in 1997.

Since then, the world's population has grown, and healthcare has improved. Based on those facts alone, you'd expect someone else to reach Calment's record, but nobody has, at least as far as scientists know. So why hasn't anyone outlived her in the last two decades?

The world's oldest known person, Jeanne Calment, died in 1997 at age 122. Image: AP Photo/Files, Francois Mori

"I personally am quite pessimistic about it," author Jan Vijg of the Albert Einstein College of Medicine in New York said, when I asked him whether we could ever expect our lifespan to stretch beyond 120 years. "It seems to me, based on what we know, not possible," he continued. "But if you ask if it's impossible, I cannot tell you."

Jay Olshansky of the University of Illinois at Chicago, who's written an analysis piece accompanying the Nature paper, agrees that there are natural limits to the human lifespan—but he thinks we can find a way to beat them. He's one of several researchers involved in a trial that, when it gets going, will be the first of its kind, as it will target aging directly. They propose to test a drug called metformin that seems to have some powerful anti-aging properties (in mice anyway).

If that trial is successful, we might be able to break the ceiling on life expectancy that nature appears to have set out for us.

"I think [Vijg] is right that there are limits to how long we can live," Olshansky told me.

"Can we overcome them? Yes."

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Nobody perfectly understands what causes us to grow older, Vijg told me. His research focuses on "the possibility that aging is caused by genome instability," he explained, meaning that DNA mutations build up over time in our cells until they eventually result in cancer or some other problem that kills us off.

But aging is not fixed across species. Different creatures do it at different rates: a mouse will live for two or three years. A human will live for 80. A Greenland shark, the longest-lived vertebrate we know of, might live as long as 400.

Species exist to reproduce, and how long a creature lives really depends on when it has babies. Animals with delayed reproduction tend to live longer, Vijg explained. (Female Greenland sharks don't have their first litters until they're 156 or so.)

"Life works through reproduction and change—diversity," Vijg said. "Nature isn't interested in keeping a particular organism alive forever," just until it produces a next generation. Then that creature can die, and the world will go on.

We individual humans, though, aren't so comfortable with that.

Read More: Living Forever Has Never Been More Popular

If there's no limit to biological age, or if we haven't reached it yet, it would make sense that the oldest among us would be seeing the biggest increase in survival rates. But, according to the Nature paper, that isn't happening. Vijg and co-authors looked at data from the Human Mortality Database, which includes almost 40 countries and regions.

They found that the greatest improvement in survival among the most advanced age groups peaked around 1980. And it hasn't really budged since.

They then looked at the the oldest-living people in France, Japan, the UK and the US, countries that have the highest number of recorded "supercentenarians": people who live to be 110 or more. They found that age of death plateaued around the same time as Calment died, in or about 1997. Since Calment's death, "maximum lifespan for humans has regressed," notes Olshansky in his accompanying paper.

I asked Dr. Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine, who's behind a long-running study of centenarians, what makes people who live a century and beyond so unique. The answer seems to be in their genes. "We had a 110-year-old woman who smoked for 95 years," he said. In a 2011 study, Barzilai and co-authors found that lifestyle factors had basically no effect on living a super-long life among this group.

If we want to live beyond nature's limits, we'll need to target the rate of aging directly

That doesn't mean the rest of us should abandon diet and exercise, just that there seems to be something special about these people: it's as if centenarians age more slowly than the rest of us do. And so, the thinking goes, if we want more people to live beyond nature's limits, we'll need to target the rate of aging directly.

Some believe that the end of aging will be made possible through gene hacking. Vijg wouldn't deny that some sort of future technology could dramatically extend lifespan, although he considers it "highly unlikely," as he told me. "The ceiling is determined by so many different genes, and gene variants, that I simply wouldn't know where to begin," he said. "You'd have to target too many processes."

We haven't figured out how to target aging like this, at least not yet. Our increase in life expectancy so far "has nothing to do with a modified rate of ageing," Olshansky writes in his commentary. It can instead be pegged on improvements in public health, he argues.

"Without further medical breakthroughs," Olshansky writes, "life expectancy cannot continue to rise by much."

Such a breakthrough could be around the corner, in the form of a commonly used drug called metformin.

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Metformin has been available for decades as a way to help type 2 diabetics control their blood sugar levels. Surprisingly enough, it's also been shown to improve lifespan and "healthspan," or the number of healthy years lived—at least in mice.

"Metformin lowers the rate of living," Dr. Michael Pollak, a cancer oncologist at McGill University in Montreal and author on a 2013 paper that reached this conclusion, told me recently. In other words, the drug seems to approximate what Barzilai has seen in centenarians.

Barzilai, Pollak and Olshansky are all collaborating on a trial that, once it gets off the ground, could see thousands of elderly people taking this drug (or a placebo) to see if it can slow the rate of aging in humans, as it seems to do in lab animals.

Image: Shutterstock

Metformin has been around for a long time, and has already been taken by many people, so regulators have a lot of data on its safety. But that's also a hurdle in getting the trial going. "Drug companies don't want to sponsor it, because it's generic," Pollak said. That means there wouldn't be much money to be made. (Barzilai told me they're in the process of applying for grants to fund the trial.)

If metformin or something else does manage to slow how quickly we age, well, it could change the way major diseases are managed. Here's the thing: in the developed world, most people will die from either cancer, heart disease, neurodegenerative disease, or infection. All are closely tied to aging. And knocking each of these diseases out, one by one, isn't really effective: It's like playing Whac-A-Mole. If a doctor cures a patient's cancer, she will probably die of something else in one or two years. At a certain age, even the common cold can be deadly, because the immune system degrades with time.

"If we continue going after one disease at a time, as though they're all independent, we'll increase frailty and disability as a result," Olshansky said. "There may be a heavy price for not slowing aging." (Barzilai has pegged it at $7 trillion.)

So what would death look like, in a world where a drug staves off old age? Something would eventually kill you, but hopefully you'd spend less time infirm before it came. Among the centenarians Barzilai studies, "it's not only that they live longer. They're healthier longer," he said. "When they get sick, they die soon after. They don't linger."

For now, it's possible we've reached the limits of the human lifespan, and that no one will outlive Jeanne Calment. To take the average human lifespan farther—to stretch it out to 100 years and beyond—will require a shift in thinking that treats aging not as a natural process, but as a disease, to be targeted with a drug (or some other intervention).

"I am optimistic that it's not only possible, we can do it," Olshansky said. "And we should aggressively be pursuing it."

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