Thesis 43

Thesis #43 – Experimental manipulation of the forces of natural selection is one of the most powerful methods of studying the biological foundations of aging, because it can direct experimental evolution to produce extensive genetic differentiation with respect to both the rates of aging and the cessation of aging.


Though there are a variety of ways in which evolutionary biologists can usefully study aging, there is one that is central.  That is the use of experimental evolution to produce extensive differentiation in patterns of aging, with respect to both rates of decline in age-specific mortality or fecundity as well as the cessation of such declines.  Experimental evolution of aging has been achieved with many populations from the genus Drosophila, as well as on a lesser scale in other species, including the laboratory mouse.

The reason why this particular experimental paradigm is so important is that it can be used to generate well-replicated material to which the full armamentarium of biological research can be applied.  Here is what has been accomplished with Drosophila populations with experimentally evolved differences in aging:  (i) extensive tests of the basic Hamiltonian theory for aging; (ii) tests of the alternative evolutionary genetic mechanisms that might underlie the Hamiltonian evolution of aging; (iii) extensive characterization of the aggregate physiology of slowed aging; (iv) initial characterization of the physiological transitions involved in the cessation of aging; (v) genetic and whole-genome characterization of the molecular genetic foundations for aging.  Some, but by no means all, of this work is summarized in the book Methuselah Flies.

Much more work of this kind could be done with experimentally evolved populations of Drosophila, but of greater interest would be a comparably extensive project using a small mammal.  This is because we are mammals.  If we are to acquire extensive and detailed information about the functional genomic foundations of our aging, a readily bred and housed mammal would be the best system with which to do so.  I spent fifteen years arguing for such work, from 1984 to 1999.  Over the last decade, I took a break from this mission to focus on the demographic and genomic extension of my work with fruit flies.  But now that we know how effectively genomics can be applied to products of experimental evolution with very different rates of aging, I am all the more convinced of the salience of pursuing similar research with mice or some other readily maintained laboratory mammal.  Naturally, this work should be conducted with all due care where potential artifacts and problems are concerned, such as inbreeding and the use of overly novel environments.  But it has been relatively easy to apply experimental evolution to the problem using fruit flies; properly designed and replicated mouse studies could yield results of much greater medical significance, even if they are unlikely to be of comparable scientific value given they cannot be carried out on the same scale as the Drosophila work.

But while we are waiting for the results of such a necessarily protracted mouse evolution project on aging, the question remains what evolutionary thinking can offer us as a means of ameliorating our aging immediately.  The remainder of the 55 turns to this challenging question.

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