Does Aging Stop?

[FEATURED ARTICLE]

Cryonics, February 2013

By Laurence Mueller, Cassandra Rauser, and Michael Rose, New York: Oxford University Press, 2011.

Book Review by R. Michael Perry

The book here reviewed is a technical study on the effects of aging, mainly using fruit flies as a model, since these creatures are short-lived so that research involving many generations is feasible. The findings appear to have relevance to other animal species, including humans.

It is customary to think of aging as a process of progressive deterioration, akin to rust, that finally ends the life of the organism. The growing disability and decline in health, it is said, is reflected in an ever-increasing mortality or chance of dying in a given time interval. Not so, say the authors. Instead, though mortality does increase throughout much of later life in organisms ranging from insects to humans, finally but definitely it plateaus or levels off to more or less a constant value—aging stops. After this death still occurs, but at a nearly fixed rate, and the organism in this “late life” period does not experience any additional ongoing deterioration. Aging is not really a “process,” say the authors, but is best understood as a result of decreasing selection pressure as the organism repeatedly reproduces and the need for its continued survival correspondingly diminishes.

The absence of selection pressure, the authors say, means that features of the organism that are both beneficial and not subject to deterioration with time, that is to say are age-independent, persist unchallenged through time, allowing the late life period of little or no further deterioration to emerge. This theory was first developed by William D. Hamilton in the 1960s, and is invoked throughout to explain the extensive experimental findings based mainly on the life histories of fruit flies.

The work reported with fruit flies (Drosophila melanogaster) was long and extensive, covering 18 years and 465 generations, supplemented by a lesser amount of work with a related, also shortlived insect, the medfly (Cerititis capitata). The fruit flies averaged about 14 days per generation and lived up to a little past 100 days. Roughly, the length of generations and maximum life-span of the fruit flies in days equaled these data for humans in years, which thus are scaled several hundred times longer.

As for the results, it is consistently shown that the mortality of fruit flies, measured in terms of a probability density function giving the chance of dying in a short time interval, does not indefinitely increase. Instead it levels off or plateaus in later life, approaching a roughly constant value in which about 15-30% of the flies die per day, the variations depending on such factors as whether the flies have been specially bred for longevity. Though this is a substantial attrition rate, it is significant that it does not change much from this point on and particularly does not approach 100%, contrary to the thinking of earlier times. Instead, following the period of “aging” in which mortality rates rise, there is a period of indefinite if still finite length that the authors call “late life” when the organism does not age any further, though the aging that has already occurred is not reversed. The study was extended to cover fecundity, measured by the number of eggs produced per female fly per day. Here too it was found that rates plateaued at nonzero values, in this case about 1-5 eggs/day, starting around age 60 days, versus about 50 eggs/ day at peak performing ages of 20-30 days. The plateauing, both of mortality and fecundity, was highly insensitive to such effects as whether the particular strains of flies were shorter-lived or longer-lived, or had started out longer-lived and been selectively bred to be shorter-lived.

The authors note that other explanations for the onset of late life than the one they offer (Hamilton’s theory of diminishing selection pressure with time) have been proposed, and detail their considerable efforts to rule out these other explanations. Thus for example, there is a heterogeneity theory: a population of individuals contains some that are more likely to live long than others due to genetic variations. As the population ages, the shorter-lived variants die off leaving the longer-lived who then drive the mortality to lower levels than would otherwise occur. This hypothesis is carefully tested, however, and the authors find that selection pressure works against heterogeneity by pruning the less fit, enforcing a uniformity that defeats this explanation of late-life plateauing.

The study was done with flies, though we are naturally more interested in ourselves, and particularly, whether humans like flies have a late-life period of indefinite duration in which aging has ceased. Humans, though, are much longer lived, and even a short-lived mammalian cousin such as the mouse would present formidable obstacles for laboratory research, requiring about a century to carry out a study to the same limit (465 generations, 12 weeks each in this case) as was done with the fruit flies. The authors caution against using human demographic data with the same confidence as data from the carefully controlled experiments they and others have undertaken with insects. The decline in mortality with age nevertheless occurs in other species too, the authors note, so that with humans in particular mortality has been found, tentatively, to reach a constant somewhere in the age range of 90-105, with roughly 50% of individuals (both genders) dying per year from then on. The authors conclude that late life in humans is broadly in line with the Hamiltonian theory, though the details of what is happening physiologically are complex and still not well understood.

But the authors pose the question: why does late life in humans begin so late? Moreover, could it be induced to happen earlier, when one’s health is much better and mortality much smaller? The hypothesis is considered that the transition from aging to late life occurs so late because of an agricultural diet, to which humans are still imperfectly adapted after some 400 generations or less. Here there are arguments and counterarguments, and the authors caution that more research is needed to test this and some alternative explanations for the lateness of late life. Still, the authors speculate that aging might be made to stop earlier by adopting a huntergatherer diet like that of our preagricultural, paleo ancestors. In any case, proclaim the authors, “gerontology based on cumulative damage or programmed aging is defunct.”

One consequence is that attention must shift, in the fight against aging, from the idea of stopping a small number of forms of cumulative damage, as Dr. Aubrey de Grey has proposed, to recognition of the need to induce late life earlier. The failure to take this latter approach, say the authors, will mean that far too many forms of damage will have to be addressed on an individual basis for any practical antiaging program. As an alternative, the authors propose experimental evolutionary studies in which aging in model species is made to stop earlier and earlier, with corresponding adjustments in the rate of aging, and close study to determine the physiological and biochemical reasons why the changes occur. Such work would step beyond the authors’ own, reported in the book, in which the organisms were treated largely as black boxes in monitoring survival and fecundity. The extra effort, they say, should provide superior insight into halting aging in humans.

One thing stressed in the book is that the hypothesis that aging stops was recognized—and resisted—long before it was widely accepted. Indeed, the present volume is largely an effort to establish this simple hypothesis beyond a reasonable doubt. The large amounts of evidence, both experimental and theoretical (using simulations of fly evolution and related calculations) and the thoroughness with which it is treated will be of interest to the researcher, while by the same token this is not a book for the general public. Such a book in turn might include a chapter summarizing the work covered in the present volume, then go on to cover other topics relating to the aging puzzle and its possible resolution, some of which are yet to be researched. I also think the work of Dr. de Grey, which is mildly criticized near the end, may actually have synergistic value, serving as a useful complement to the antiaging approach advocated here and others that might be attempted.

In any case, the book makes a very persuasive case that aging stops in fruit flies and medflies. It may also stop in humans, but if so it is at such an advanced age, with so high a final mortality, as to be of little benefit. Could human aging be stopped at an earlier age where the mortality would be much lower? And does abandoning the agricultural diet of the past 10,000 years have a significant chance of bringing this about, as the authors very tentatively suggest? To me the jury is still out—more evidence is needed—though admittedly I am skeptical. Our paleo ancestors generally did not live as long as we do. When causes of death such as infant mortality, childhood diseases, malnutrition, predators and adult diseases are taken into account, I still don’t see strong evidence that their aging stopped much earlier than ours. An earlier halt to aging will surely take more than a simple change in diet, one would think. As usual, further investigation is called for.