Sci. Aging Knowl. Environ., 17 December 2003
Vol. 2003, Issue 50, p. bb3
[DOI: 10.1126/sageke.2003.50.bb3]


Aging by Numbers

A review by Thomas B. L. Kirkwood

Longevity: The Biology and Demography of Life Span
By James Carey
Princeton University Press, Princeton, NJ, April 2003. 304 pp. $29.95 (paper). ISBN 0691088497

James Carey's new book, Longevity, is an account of more than a decade of work with a Medfly resource in Mexico that changed scientists' view of extreme old age. Researchers and geriatricians have defined aging as a progressive, generalized impairment of function that leads to increasing frailty and vulnerability to death. This description fits our common experience of the aging process as a one-way street along which the going gradually gets tougher until, with increasing likelihood, some critical life-support system fails, and we die. Thus it came as a considerable surprise to many when, in 1992, two reports in Science described how, beyond a certain age, the mortality rates of both the fruit fly, Drosophila melanogaster, and the Medfly, Ceratitis capitata, no longer increase and even show a late-life decline. These so-called mortality plateaus were heralded as the death knell for the widely observed Gompertz model, an exponentially increasing age-specific death rate. Some also saw them as a challenge to evolutionary explanations of aging, which suggest that natural selection is powerless to influence survival at very old ages (see Williams Classic Paper).

Longevity synthesizes a huge body of data collected over a long period of time, making this work unquestionably without parallel. Furthermore, Longevity is an exceptionally well-written and thoroughly analyzed treatise on some of the most important general questions in biodemography: How does the pattern of reproduction and individual longevity vary from fly to fly within the population? Are reproduction and longevity related, as evolutionary theory predicts? Does the pattern of egg laying in early life affect fecundity later in life? Are reproduction and longevity linked in a similar manner in males as in females? What is the effect of population density on reproduction and longevity? And so on.

Longevity rests on Carey's work as team leader of the Medfly project that brought the mortality plateau to light. He might never have made this observation had it not been for an extraordinary facility in northern Mexico that had been established to counter the economic threat posed by the Medfly to the fruit growers of the southern United States. Vast numbers of sterile Medflies were--and are--routinely produced in a factory-scale rearing facility near the city of Tapachula and then released in fruit-growing regions of the United States as part of a biological control program. The enormous scale of production meant that members of Carey's team could easily use sample sizes of 100,000 or more for their experiments. Such large sample sizes are important because the mortality decline can be seen only in the very longest-lived flies, which represent a tiny fraction of the total number of insects in the experiment. The great majority of flies die during the phase when mortality rates are still increasing.

In trying to tease general messages about individual life-history patterns from the extensive data on populations, the author faced an immediate difficulty: how to represent these extraordinarily heterogeneous data. To solve this problem, Carey devised a graphical technique that he calls an "event history diagram." Like many clever ideas, the principle is simple and powerful in equal measure. Scientists usually portray longevity data in the form of a survival curve, plotting the surviving fraction on the vertical axis against age on the horizontal axis. However, this information--and more--can be described in another way. If, for each individual fly whose death is recorded, one takes a thin straw, cuts it to the length that represents the age at death of that individual, and then lays the straws one on top of the other in order of diminishing length, then the curve obtained by tracing the right-hand ends of the straws is the survival curve. If one then colors or shades each straw to indicate the phases in the individual animal's life when it was reproductively active, perhaps even indicating the rate of reproductive output (egg-laying level) as well, one ends up with a picture that shows not only the survival of the population but the patterns of life-history events as well (Fig. 1). These event history diagrams take little practice to read, and they are remarkably informative. For example, one can see at a glance that high egg-production days were noticeably absent from the longest-living flies, those that lived beyond 60 days.

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Fig. 1. Knowing much about history. Event history diagrams for survival and reproduction in five cohorts of 100 females. Each horizontal line represents the life course of an individual fly, the length of which is proportional to its life span. Segments within each lifeline are color-coded to depict egg-laying levels at each age: green = 0 eggs, yellow = 1 to 40 eggs, red = 40+ eggs. Control A (top) and Control B (second from top) refer to flies maintained throughout their lives on a sugar-only and a normal diet, respectively. The symbol t denotes the time at which sugar-fed cohorts were fed a full protein diet. [From J. R. Carey, P. Liedo, H.-G. Müller, J.-L. Wang, J. W. Vaupel, Dual modes of aging in Mediterranean fruit fly females. Science 281, 996-998 (1998).] [Abstract] [Full Text]

The life-history insights that unfold in the major chapters of the book are, overall, quite complex. For example, when investigating the patterns of individual reproduction within the population, Carey and colleagues found that the results were highly variable. In cohort studies, they noticed tradeoffs between early and late fecundity and early and late mortality. However, early reproduction and subsequent fecundity and longevity did not generally correlate in individuals. These apparent contradictions can best be understood by noting that, if the individual patterns play out differently across time, the cohort average will not necessarily resemble the "typical" pattern of the individual. One curious instance of heterogeneity in reproductive patterns is that egg laying generally declined with age, but long-lived flies experienced several successive peaks of egg laying at intervals of about 3 weeks. The ways in which costs of reproduction play out were also complex. For example, when mated and virgin females were compared in terms of mortality, virgins showed lower mortality until 16 days of life, then higher mortality until about 50 days, and then about the same mortality as mated flies through the remainder of the life span.

One of the most intriguing questions about mortality plateaus, which ought to be amenable to the kind of fine-grained biodemographic analysis presented by Carey's research, is the extent to which heterogeneity within the population is at work. If the mass population contains subpopulations that are much more robust than average, then as the less robust flies die in the early weeks of an experiment, the robust ones will remain to dominate the dwindling band of survivors. In principle, this effect is sufficient to explain mortality plateaus. But does the requisite heterogeneity actually exist, and if it does, what causes it? Carey devotes considerable attention to the question of heterogeneity and presents much interesting material, but by the end of the book one is left with the feeling that the issue is still not entirely resolved.

One test of the heterogeneity hypothesis is based on the tenet that, because high density increases mortality over that of more sparse populations, maintaining a population at high density might intensify the mortality differential between robust and frail subpopulations and alter the timing of any mortality plateau. It was found, however, that the leveling off of mortality at the highest ages is independent of density. This observation might indicate that heterogeneity is unimportant, but it's hard to be sure. The work discussed in Longevity does not include experiments that attempt to identify the molecular lesions that underlie individual aging processes, and, therefore, it is not yet possible to link life-history events, particularly senescence, with biomarkers of heterogeneity that might ultimately resolve the issue. In time, there needs to be a coming together of the biodemography effort and research on basic mechanisms of aging (see "Aging Research Grows Up").

Rather surprisingly, the last three chapters of the book leave the Medfly data behind in order to develop some general biodemographic principles of aging and longevity. The musings are something of a leap, as this section focuses mainly on social species, in particular, humans. Carey advances a range of ideas about the role of family structures and intergenerational transfers in the evolution of the human life history, with its recently extended postreproductive life span. All of this is a long way--biologically and biodemographically--from Medflies, and the formal rigor of the early chapters is lacking. Although Carey's suggestions have some intuitive appeal, we know from detailed studies of the evolutionary basis for menopause that such ideas must be tested in strict quantitative terms before they can be accepted (see Holmes Perspective).

On balance, Longevity is a fine addition to the growing collection of books on the biology of aging, but it is a book of two parts. Part one--on the Medflies--is a detailed record of experimental work, a topic that deserves close study. The fine-grained detail of the experiments and analyses described herein make this part of the book well suited to researchers in the field of aging, who are attuned to the nuances of the subject matter. Part two--on the evolution of the human life history--will appeal to a broader audience. However, the nonspecialist reader should be cautioned that this section is more speculative. For the specialist, part two is worth reading, if only to provoke the reader to further research on this gripping subject.

A PDF of chapter 1 is provided by Princeton University Press.

December 17, 2003 Citation: T. B. L. Kirkwood, Aging by Numbers. Sci. Aging Knowl. Environ. 2003 (50), bb3 (2003).

Science of Aging Knowledge Environment. ISSN 1539-6150