Wednesday, June 18, 2008

Rose on Evolutionary Biology and Aging

Two weeks ago I was in Vancouver for the 2008 Congress , giving this talk and this talk, respectively, to the Canadian Philosophical Association and Canadian Political Science Association.

On the flight to and from Vancouver I read Michael Rose's excellent book The Long Tomorrow. And I wanted to make a few notes about the book here for my future reference.

Rose is Professor of Evolutionary Biology at the University of California, Irvine. You can watch a very engaging presentation by him here.

On his web page he lists among his interests “the evolution of aging and immortality”. No doubt the latter is likely to raise some eyebrows! And longevity science would profit from having more bold and imaginative thinkers like Rose.

The Long Tomorrow is a very accessible and engaging book. It’s a fascinating read on many different levels: taking us through Rose’s work on evolution and aging; providing us with unique insights into the way science and scientists work (e.g. importance of getting funding, the hostility many have to the notion of extending the human health span, the time it takes to complete longevity experiments); and also providing us with a glimpse into Rose’s own personal life- his dedication to work, the family tragedies he has faced, etc.

Rose pursued his PhD at the University of Sussex, where he worked on aging and fruit flies. He recounts coming across an article by J. M. Wattiaux, whose work focused on the effect of parental age on the offspring produced at that age (see this, for example).

Wattiaux’s results lead Rose to the importance of the force of natural selection. Rose claims:

Natural selection discards bad genes, genes like those that cause fatal childhood progeria. Bad genes cause these effects by producing inborn errors of metabolism: letting toxins accumulate, impairing brain function, and so on. Many of the diseases that kill infants are the products of such bad genes... Natural selection keeps genes with such devastating early effects rare, because the afflicted individuals die before reproducing. Bad genes destroy themselves when they kill the young…. But at later ages, the force of natural selection becomes weak. It leaves genes with late bad effects alone, because natural selection has stopped working. Its force has fallen toward zero. Bad genes that only have late effects will not be removed by natural selection. They can accumulate. There is no more automatic Darwinian screening (p. 42).

And the force of natural selection, argues Rose, is set by the age at which reproduction first occurs in a population. The force of natural selection is strong before the age of reproduction. Thus, if reproduction is postponed, the force is high longer. And this lead Rose to what he calls “the single most important breakthrough in the long history of research on aging: the deliberate creation of long-lived animals” (p. 43).

Given how long aging research takes, it makes good sense to test the claim about age of reproduction and longevity on a species that doesn’t live very long. And this is where the fruit fly becomes very important. And Rose created Methuselah flies, flies that postponed aging by reducing early fertility.

The creation of the Methuselah flies thus revealed the tradeoff between reproduction and survival. Rose notes numerous examples as evidence of this tradeoff. Pacific salmon, for example, die immediately after reproduction. However, if they are castrated they can live years longer than intact salmon. The same is true of soybean plants. Rose contends that this tradeoff is also evident in humans. For example, he notes (p. 57) that twentieth-century eunuchs, who were victims of eugenic legislation (because of their low IQ), actually had their longevity significantly increased. And so these kinds of data explain the evolution of aging:

...genetic tradeoffs between later and early ages. Specifically, early reproduction tends to trade off against later survival. And since the weakening force of natural selection tilts the balance against later survival, evolution will tend to produce oversexed youth and decrepit old age, because it favors genes that enhance early reproduction at the expense of later survival. (p. 60)

Rose also notes other factors that influence longevity. For example, body size (p. 64). Animals come in a variety of different sizes. And most (but not all.. dogs, for example, are an exception to this) large animal species live longer than smaller animals. Why is this so? Why do cows and pigs live longer than mice and rabbits? Why do the latter not possess the genetic potential to live as long as humans?

External environmental hazards play an important explanatory role in this story. And so Hobbes’s insight that life is “nasty, brutish and short” in the state of nature, does not equally apply to all species. The smaller you are, the shorter your life tends to be. And the reason for this is that there exist greater threats to your long-term survival.

The number of predators that threaten an animal's existence will decline the larger an animal is. Thus these larger animals will tend to live longer. And “if a species lives longer in nature, the force of natural selection will be increased at later years. Larger organisms can reproduce at later ages because they are more likely to be alive then, so the force will remain high at later ages. This fosters selection of genes that will tend to keep the larger alive still longer.” (64-5).

Rose also notes that, in addition to large animals, flying animals also enjoy greater longevity. And the reason for this is that they are better able to escape predators. They can also fly vast distances to find food. And so flying animals tend to live longer in the wild; thus they have more chance of future reproduction. “[A]ll else being equal, the force of natural selection favors the continued survival of flying animals more than those that can’t fly. Thus evolution produces parrots that can easily live 60 years, if not longer, while rodents of the same size that don’t fly die in six years” (p. 65).

In addition to body size and wings, having a thick shell (like turtles do) helps a species live longer. “Having a thick shell is an evolutionary anti-aging device, because it reduces mortality and thereby increases the force of natural selection at later ages” (p. 66). I love the way Rose describes the turtle’s shell as an “evolutionary anti-aging device”. For many opponents of longevity science object that retarding aging is “unnatural”. To which we can point to turtles and say “Anti-aging devices occur in nature as well!”

Indeed, a central insight that Rose emphasizes throughout the book is that evolution shows us “the vast potential for altering aging physiologically within one generation, without changing genetics” (p. 69). And the fascinating example of honeybee queens illustrates this point. The queen can live longer than five years, while the worker bee often dies after a few months. While in their eggs both bees have the potential to develop into queens. But queen bees are fed a royal jelly that triggers a series of physiological realignments in the bee.

Rose provides a great analogy between evolution and the production of Ford cars in Chapter 12. And the analogy reveals why it is that we have the limited lifespans we currently have. Here it is:

Think of the automotive industry. Henry Ford sent one of his engineers to a scrapyard to find out which parts of defunct Model T’s still had some usable life left. When the engineer reported back with a list of the durable parts, Ford instructed his engineers and suppliers not to make those parts to such high specifications. Ford didn’t want to waste money making parts so good that they outlasted the rest of the car. This strategy culminated in “planned obsolescence”, an ugly tradition in American manufacturing… Evolution is regrettably similar. (p. 91)

Chapter 13 is entitled “Woody Allen and Superman” and in this chapter Rose turns to the provocative idea of “immorality”. He notes that centenarians do not usually lead lives of great debility (p. 101). Rose cites some important papers (authored by “the gang of Jims”) which establish that aging stops, or even reverses, at late ages. The experiments published here showed that a nonaging phase of life followed aging. This is truly fascinating! And I was not aware of this.

Rose and Larry Mueller then published this 1996 paper which showed that aging was followed by a period in which death rates did not increase. How does this translate to aging humans? Rose explains:

Over 95 years of age, human mortality rates stop increasing exponentially with age. Our death rates are phenomenally high in our nineties. But the only reason so many people survive into their second century is that there is an end to the rampant acceleration in death rates that occurs from age 15 to 90….Aging is not an infinitely high wall on mortality, rising faster and faster as we get older, until everybody is dead. It is a ramp that takes us from a phase of low childhood mortality to a much later phase of high, but relatively stable, mortality. Postponing, retarding, or otherwise mitigating aging does not require pushing back a wall of death of infinite height. It requires smoothing out a ramp of mortality, and possibly lowering the height of the top of the ramp (p. 108-9)

Where do all these amazing discoveries leave us? How close are we to actually developing an anti-aging intervention for human beings? Rose characterizes things this way. From all of human history until 1980, the prospect of postponing human aging was negligible. From 1980 to 2000 those prospects were hopeful but not outstanding. Since 2000 (with the sequencing of the human genome), the prospects of postponing human aging have become excellent.

And this is why I personally believe that longevity science could lead us to the greatest medical breakthroughs of this century. Rose’s book is a must read for those interested in evolutionary biology and aging. And as I noted above, the book is very accessible to non-scientists and provides many rich insights into the workings of fruit flies, humans, science and many other things. Reading The Long Tomorrow has further strengthened my conviction that moral and political philosophers ought to seriously consider the implications of longevity science. Otherwise we risk letting dogma and fear delay the imperative to increase the opportunities for healthy life. If more philosophers paid attention to the exciting scientific work being done in this area, then we could help bridge the unjustified divide between political philosophy and science policy.


P.S.- Those interested in aging research should check out this site for information on the "Aging: The Disease, The Cure, The Implications" Conference at UCLA on June 29th.