Changing hypotheses
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.
A Superman effect?
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.
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