Thesis #28 – Among such experimental populations evolving greater levels of adaptation at later adult ages, evolutionary changes in (a) structural gene frequency, (b) gene regulation, (c) patterns of cumulative damage, and (d) still other features of physiological function will reveal the mechanistic changes required to enhance adaptation at later ages in that species, and thereby ameliorate its aging.

Laboratory populations that have evolved greater levels of adaptation, and thus prolonged survival, during adulthood are key material for unraveling the conundrums of aging.  If the views articulated here were NOT correct, it wouldn’t be possible for experimental evolution to turn aging around on a dime by delaying the decline in the forces of natural selection.  Instead, the nostrums of molecular biologists would readily and easily postpone aging.  But they don’t.  Thus biomedical research on aging should focus on what evolution does when it slows or postpones aging.

So there now exist material embodiments of re-tuned aging:  Methuselah Flies that have much greater lifespans, both average and “maximum” (where the definition of the latter is a problem that we will discuss later in the 55), as well as better sustained fertility.  As such, we can directly examine just what it takes to re-tune aging, at every level:  genetic, biochemical, molecular, cellular, organ, and whole-organism.

My laboratory has already released an entire book on the experimental characterization of how these Methuselah Flies are able to live and function longer (Methuselah Flies, 2004; Rose, Passananti, & Matos, eds.; World Scientific).  That would be the work to read for an introduction to these flies.

But let me give a crude overview of what longer-lived, longer-reproducing, fruit flies are like.  They have changes at many genetic sites distributed throughout their genomes, NOT changes at just a few genes.  This means that genetically engineering or pharmaceutically manipulating human biochemistry to achieve radically greater lifespans is not going to be a feasible project.  There are too many targets Instead, our physiologies have to be re-tuned at many levels, and in complex ways.

Some of this physiological complexity is starting to emerge from careful work on fruit flies with improved aging.  Here are some characteristic features of longer-lived fruit flies:  greater resistance to acute stress, greater physiological reserves, normal metabolic rates, better maintenance of physical activity, greater athletic endurance, greater reproductive restraint under bad conditions, and so on.

A number of molecular biological hypotheses about aging have been tested in these flies.  While the failures to corroborate these institutionally favored hypotheses have consistently NOT been published, because at least some molecular and cell biologists exhibit little commitment to strong-inference science, I can tell you that there is significant unpublished research on these flies which falsifies favored reductionist hypotheses.  To a first approximation, it would be fair to say that these flies have served as a nemesis for conventional molecular and cellular theories of aging.  Overall, the reductionist theories of aging appear to be systematically worthless, of no better than incidental validity, from the evidence of experimental evolution.  Which is just as evolutionary theory suggests they should be.