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August 23, 2011

Michael Rose talks about different aging theory

Michael Rose key point - Since Aristotle, virtually everyone who has worked on the biology of aging has conceived of it in terms of an underlying cumulative physiological process. But Michael Rose does not think aging is a cumulative process anymore. Michael Rose bred long lived fruit flies that live 4 to 5 times longer than normal fruit flies.

His present view is also not one generally held, at least not yet, even by most evolutionary biologists who work on aging.

Theory - Aging processes can be halted and deathrates can plateau. This level can be manipulated.

My turning on the Road to Damascus started one day in 1992 when my good colleague Larry Mueller showed me two articles from the journal Science, articles from the laboratories of our colleagues Jim Curtsinger and Jim Carrey. The data in those articles were mind-blowing. They showed the complete cessation of the acceleration in age-specific death-rates that evolutionary biologists like Larry and myself regarded as the hallmark of aging. It looked as if aging came to a stop.



This led me to convince Larry Mueller to do some explicit simulations of evolution, simulations in which we looked at what happened at very late ages, long after Hamilton’s forces of natural selection bottom out and stabilize. What the simulations generated were late-life plateaus in mortality, just as the Curtsinger and Carrey labs had found. We published this result in PNAS in 1996.

With this result in hand, we then checked how changes in Hamilton’s forces would change the age at which mortality plateaus occur, based on explicit simulations. These simulations showed that changing the last age of reproduction in a biological population, the parameter that Hugh Hefner is working on as I write, would tune the age at which mortality rates would plateau.

So Larry Mueller, my then graduate student Casandra Rauser, and many undergraduate students working in my laboratory tested populations that had been evolving in my laboratory for this predicted relationship between the last age of reproduction and the start of the plateau in mortality rates. Qualitatively, it worked. Shifting the last age of reproduction, which is when Hamilton’s force of natural selection acting on mortality itself plateaus, produces the qualitatively predictable shift in observed mortality plateaus in our fruit fly experiments. Not immediately, as a physiological effect, but eventually, over many generations, as a result of evolution occurring in my laboratory under controlled conditions.

If aging is a physiological process, however multifarious, why should it come to a halt just when the organism is most debilitated? In the human case, demographic aging stops when the death rate is between 30 and 50 % per year, particularly among centenarians. These are very frail people, yet their aging abruptly stops. How is this supposed to make sense?

Instead, imagine an entirely different view. Suppose instead that aging only seems like a physiological process, but actually is no such thing. Suppose instead that aging is the age-dependent tuning of Darwinian adaptation, where the tuning is determined by the patterns of Hamilton’s forces of natural selection. Not a physiological process at all.

On this view, what seems like a physiological process is a scientific illusion, fully parallel to the illusion of the sun rising in the morning, crossing the sky, and setting in the evening. Because, of course, the sun does no such thing. Sunrise and sunset are optical illusions produced by the rotation of the Earth.

So why is this physiological illusion so convincing, and so reliable? It is convincing and obvious because the falls in Hamilton’s forces of natural selection are so predictable and so intense, at least in most animal species. Hamilton’s evolutionary forces are as strongly determinative of deterioration as any acute disease process. Only the illusory ‘physiological aging processes’ that they produce is extremely protracted in the human case.

If this view is correct, then those species in which Hamilton’s forces of natural selection do NOT fall should be free of aging. Even if they have the same basic cell biology as we do, and even if they are as subject to mechanical injury and oxidation as we are. This alternative view thus makes some strong predictions, predictions which are readily falsified by comparative data. IF, a big if, this theory is wrong.

And the comparative data show that such species DO indeed exist. For example, sea anemones that reproduce only by symmetrical fission are animal species that are thought to be free of aging, from experiments culturing them in aquaria. Similar results have been found among other fissile coelenterates, particularly in the work of Daniel Martinez. And Graham Bell has found results like these in flatworms that can also reproduce by splitting in two. So, not only can aging stop, sometimes it doesn’t even get started.

The problem for people is that when our aging normally stops, we are about a hundred years old, very fragile, and often demented. So who would want to sustain that state indefinitely?

But I kept on thinking about the cessation of aging. In the last two years I started thinking about some data that Cassie Rauser had collected on the cessation of reproductive aging in our fruit flies. She showed that the timing of this cessation, and the reproductive function of flies that have stopped reproductive aging, depended on their environment. These findings raised the possibility, in my mind, that we might be able to manipulate when mortality declines stop too, using environmental manipulation, in fruit flies or humans.

A few fruit fly experiments later, we are already seeing signs of such an opportunity: declining and stabilizing mortality too can be manipulated environmentally. This work is by Marta Santos and her team in my lab, and will be submitted for publication soon.

So, how to manipulate humans so as to stop our aging sooner, and in better condition? How to find a third option for immortalists, a less drastic choice before cryonic or cyber immortality?

As we explain in some detail in our book Does Aging Stop? (Mueller, Rauser, & Rose, 2011; Oxford University Press), shifting back to lifestyles that are physiologically comparable to those of hunter-gatherers provides a possibility of stopping aging at earlier ages, and in better shape. [For those who aren’t scientists, I have presented this possibility in some detail at the website Rob Patterson has built for me: 55theses.org.]

The possibility does present itself that we may be able to stop our aging phase, not our “aging process,” by an age like 70, and do so in much better condition than present-day 70 year-olds can sustain.

Then, as medicine becomes still better at rescuing us from the accidents of thromboses, malignancies, and car collisions, we could remain on this aging-arrested plateau indefinitely.

Thesis #55 – Once this switch to a hunter-gatherer lifestyle among older adults has become widespread, further changes that would enhance human health at later ages can be discovered using evolutionary research tools, such as experimental evolution with model organisms and the molecular genetic analysis of human evolutionary history.



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