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The Long Tomorrow : Michael R. Rose
12/19/06
The Long Tomorrow : Michael R. Rose
The full subtitle: "How Advances in Evolutionary Biology Can Help Us Postpone Aging".
This was a good book, although almost too simple in spots. Since aging is a topic I follow (and, apparently unusually, since I was fairly young), the impact of the book was more emotional than informative, though it was informative. I will explain why shortly.
The book is in part an autobiography of the author, who is a practitioner in the field. How he got involved in the rather unfashionable-at-the-time scientific study of aging, the experiments he has done, the things he and others have discovered, the reactions to the research, the surprises that he has run across, and the personal tragedies he has encountered.
One thing I was surprised to hear about was that Leonard Hayflick, discoverer of the Hayflick limit (not named by Hayflick), wherein making human, or any other animal cells divide in culture, actually fails to work after a certain average number of divisions, is a rabid opponent of the attempt to fight aging, very nearly equating such attempts with snake oil.
The book follows his academic career through a somewhat disappointing but auspicious meeting with John Maynard Smith, his hero at the time, in 1975.
Aging research then had a pretty poor reputation, the field being inculcated with more than a few charlatans, and the scientists doing more than their share of poor experiments. John Maynard Smith and others in the same vein started making the field more respectable.
Starting with work with Brian Charlesworth, Michael Rose has shown astounding loyalty to that bulwark of biological experimentation, the fruit fly Drosophila melanogaster. It is through these little critters that a number of breakthroughs have been made.
So what would an evolutionary theory of aging entail? The idea is that natural selection and crossovers/assortment/mutations either encourage aging to happen, or allow aging to happen.
Natural selection is mostly concerned with reproduction. Anything that kills before the age of reproduction will be strongly selected against. You will get the occasional awful condition of this sort, like the accelerated-age-mimicking disease, progeria, but compared to diseases that strike more at older ages like heart conditions and cancer, progeria is an exceedingly rare condition. It has been chopped out most viciously by natural selection.
Once reproductive years are over, the force of natural selection drops precipitously, which will show up as conditions that would be threatening to reproductive capability for younger creatures.
One of the first possibilities they came up with, that genetic variation was simply getting worse with age, turned out not to be the case when they did their first big fruit fly study (can you imagine working with fruit flies for 400 days straight?), at least not as measured by egg-laying capabilities. A pretty disappointing result, for the mathematical model itself was elegant. This led them in other directions.
Further experiments led them to finding out how to make "Methuselah flies", flies whose lifespans were greatly extended by allowing only eggs from more aged females to hatch from each generation.
Two of the most important indicators of lifespan for flies are reproduction and calories. Not allowing breeding results is longer lifespans. Sterilization results in even longer lifespans. This applies to humans as well, though to a lesser extent than fruit flies, as demonstrated with longer lives of the castrati. Caloric restriction, but not malnutrition, also increases lifespans, though it slows or stops reproduction as well as metabolism. Okinawans live to be 77.5/85.1 (M/F) years on average, compared to 76.7/83.2 for Japan in general. They do not live to be 140 years old, as Michael points out.
Nasty chemicals like 2DG (2-Deoxy-D-glucose) have given some of the caloric restriction benefits to rats without the actual caloric restriction, but 2DG is notoriously toxic when taken for long periods or at more than minimal concentrations. Who knows what that line of research might bring.
One note of hope Michael brings up is that according to evolutionary aging, and as found in nature, the mortality rate is not an infinitely-high wall. Creatures go from low mortality at the beginning off their reproductive years to high-but-plateaued mortality (die-after-mating creatures like Pacific Salmon excepted) past the end of their reproductive years, but it's never 100%. Statistically, you should see the occasional 110-year-old after many years of observing.
The reason that would be heartening is that you don't have to climb an infinitely high wall. You have a chance to flatten out... to reduce the mortality rate, and potentially to flatten it. This is a relatively new realization since the early 1990's.
On a slightly sour but more realistic note, there is no single gene for aging. If there truly were, we would have encountered non-aging mutants, for one. Expectations are that the number of genes involved in aging, from comparing products in old and young cells, is in the 200-and-a-bit range.
On a positive note again, we have some amazing tools in our study of biochemistry these days. Mapping genomes, figuring out what proteins they make, sheer computational power, all so incredibly much better than they used to be even a mere decade ago. It might be easier to track down those 200 or so genes to find out what's up.
On a more final, sour note is the thing that most disturbed me. Most of the people that Michael has met are unfriendly to the possibilities of extending our lifespans. Now teenagers and the like, I can understand it from them. From older people, however, the implication of this endeavour being selfish, or foolish, or futile is absolutely incredible... and depressing, if it truly is a majority view.
I do not fear death, myself (that's a personal topic for another time), but I want as much time as I can possibly have, really. Enough to travel everywhere, learn... well, not everything, but as much as I can, and to see what we can make of ourselves over the next 500 years or so.
The book's final chapters focus a little bit on what might be needed to tip larger-scale scientific anti-aging projects (as opposed to the mere pushing of non-life-extending drugs by the medical stand-in for the used car salesman) over into the public conscience. A "killer app", perhaps. There are two ways to go: big projects, or serendipity. Relying on serendipity is cheaper, but trusting your results to luck is not bound to get you as far.
The book is written is a very readable, personal style, and with a decent smattering of delightful turns of phrase. I highly recommend it. It's also not beyond your regular, educated reader.
I wish the likes of Michael R. Rose the best.
I also wonder how I could get the word out.
So what about you folks? Do you want to live a long time? If not, why not? If so, how much would be "enough"? 150 years? 200? 500?
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