In 1939, British statisticians Major Greenwood and J.O. Irwin published a little-noticed article in the journal Human Biology that contained a profoundly unexpected discovery. Greenwood and Irwin were studying mortality figures for women 93 and older. They expected to see the death rate rising with age, as it does throughout adult life. But they did not. Instead, between age 93 and 100, the acceleration in death rates came to a screeching stop. Little old ladies who were 99 were no more likely to die than those who were 93.
The authors were dismayed. “At first sight this must seem a preposterous speculation,” they wrote. After all, like every other respectable biologist of the time, they assumed that “decay must surely continue.”
But what if it doesn’t? What if aging stops? And if it stops very late in our lives, is there any way we can make it stop earlier, when we are in better health?
The fact of aging has been well known to biology and medicine from their earliest days. Aristotle wroteon the topic more than 2,300 years ago. Like pretty much every biologist since then, he thought of aging as a remorseless process of falling apart, until death finally puts us out of our misery.
Present molecular and cell theories of aging assume that aging is a physiological process involving some type of cumulative damage, disrepair or disharmony. The theories differ only over which kind of cumulative breakdown happens. Evolutionary biologists such as myself who work on aging likewise used to think that we were studying how natural selection might allow the cumulative damage to happen.
All that started to change in 1992, when the labs of Jim Carey at the University of California at Davis and Jim Curtsinger at the University of Minnesota independently published landmark articles in the journal Science.
Carey and Curtsinger studied not humans but those stalwarts of the lab, flies — hundreds of thousands of them. They kept groups of thousands of flies of the same age in carefully controlled conditions and meticulously recorded the death of every fly until the whole group was dead.
Amazingly, they found the same thing as Greenwood and Irwin. At first, the mortality rate increased exponentially. But after a few weeks, death rates stopped rising. Some of Carey’s results were breathtaking: Once death rates leveled off, there were months of stable or even declining death rates. It looked as if a relatively brief period of aging was followed by a long plateau when aging stopped. This time, everybody noticed.
Soon, other biologists were looking for signs of life after aging. To our collective astonishment, they were found in every laboratory experiment of sufficient size, whether flies, nematode worms or beetles. Admittedly, there aren’t many studies that have used large-enough cohorts to see the effect, and nobody has studied it in mice or other mammals. But that merely showed why we hadn’t noticed it before: Almost no one had thought to keep large enough cohorts to measure death rates at later ages accurately. Once we started doing experiments on the right scale, it was obvious that what Greenwood and Irwin found in their old ladies was generally true: Look late enough in the aging process and it seems to stop.
For me, as an evolutionary biologist who had been working on aging for 15 years before 1992, confronting the Carey and Curtsinger results was like a near-death experience. My mind reeled.
At the time, my view of aging was informed by the work of the great evolutionary theorist William Hamilton. Hamilton reasoned that, in early life, any gene that kills an organism before it can reproduce will be ruthlessly weeded out by natural selection, since that individual will fail to leave offspring. But genes that kill later in life are not weeded out as rigorously, so they can hang around in the population. By this reckoning, aging evolved as a result of “declining forces of natural selection” as individuals get older.
Evolutionists universally interpreted this as proof that unrelenting aging was inevitable. Yet here we were with evidence that aging actually stopped.
I spent two uneasy years thinking about the problem. Then I had an idea; a hopeful speculation. What if our interpretation of Hamilton’s work was wrong? What if aging was actually caused by the declining forces of natural selection? If so, once these forces bottomed out, the aging process too would stop.
I did not have a full explanation — it was just an intuition. But I knew how to test it.
My colleague Larry Mueller is a gifted computer modeler and statistician, as well as an evolutionist. Plus, his office is next to mine. I asked him to run some computer models of the aging process incorporating this new interpretation of Hamilton’s mathematics. My hope was that under some circumstances, evolution might allow aging to stop late in life, at least theoretically.
In every case we ran, aging came to a stop.
So we decided to push the idea further. Could we predict the evolution of different stopping points for aging? Again, the answer was yes. It turned out that the last age at which a population is allowed to reproduce over many generations is key. If reproduction stops earlier, so too does aging. Stop reproduction later, and aging follows suit. So not only did we have a theory of why aging could stop, we could test it experimentally.
Now the burden was on me and my lab. Fortunately, I already had dozens of fly populations in which we had tightly controlled last ages of reproduction for hundreds of generations. We compared the aging patterns of these different populations in extremely large experiments featuring months of daily observations of many thousands of flies by hundreds of students.
The results were striking. Exactly as the models predicted, populations with an earlier last age of reproduction stopped aging earlier and lived longer, and vice versa.
That was encouraging, but it did not rule out another interpretation that Greenwood and Irwin offered in 1939. Perhaps the end of aging is an illusion caused by individual differences in robustness. In each population of flies, there are a few Supermen, a few Woody Allens and everything in between. The feeble die off first, leaving only the super-robust. These would be the sole survivors at later ages, making it look as if aging has sharply decelerated.
Biologists have been looking for this “lifelong heterogeneity” for years but have yet to find it. My doctoral student, Cassie Rauser, did a series of experiments but found only evidence against it. For now, only the model that Mueller and I proposed has significant experimental support.
We still don’t have a full explanation of the underlying genetics of the cessation of aging. One possibility is that there are genes that are advantageous early on but damaging to health later in life — an effect called “antagonistic pleiotropy.” We are making progress on this, but in any case the fruit fly experiments tell us that the effect is real.
We now understand that aging is not a cumulative process of progressive chemical damage, like rust. It is a pattern of declining function produced by evolution. Aristotle was wrong, and so are all the present-day biologists who try to explain aging in terms of biochemistry or cell biology alone.
Rose is a professor of evolutionary biology at the University of California, Irvine and a co-author of “Does Aging Stop?” This article was excerpted from a longer version published by New Scientist magazine, which can be found at www.newscientist.com.