Evolutionary Anthropology 13:82–88 (2004) CROTCHETS & QUIDDITIES Ponce de Leon and the Telomere of Youth KENNETH WEISS The explorer went to the ends of the earth looking for immortality. Did he only tion are indirectly screened through have to go to the ends of his chromosomes? their life-history effects. One net re- sult is that species have characteristic aging rates, making questions like, “If the drug industry has a commer- “How long do dogs live?” evolutionar- cial Holy Grail, it might be an anti- ily meaningful. Perhaps the fact that aging pill, one that would let you live lifespan is a somewhat colloquial longer and prolong your youthful rather than scientific term has led to vigor,” wrote Gina Kolata in a recent the notion of that each species has article in the New York Times.1 Genes what has been called a Maximum have recently been found that have Lifespan Potential (MLP), so that in- similar effects on aging processes in dividuals who avoid exogenous causes yeast, flies, nematodes, and humans. of death-like predation or infection This suggests that aging might be an will eventually succumb to a species- easily modifiable phenomenon and specific internal clock at its MLP, the drug industry is eager to discover making room for a fresh generation. the magic potion for eternal youth. We can illustrate aspects of life-his- Of course the icon of the search for tory evolution by the survivorship the Fountain of Youth is Juan Ponce, curve, the age-specific probability of known as Ponce de Leon. A comrade Figure 1. Ponce de Leon in his younger surviving from birth to each age (Fig- of Columbus, who successfully fought years. ure 2). The impression that there is an the Moors and helped subjugate His- MLP is an understandable illusion of pan˜ ola as a base for Spanish con- such data (Figure 2, first 2 curves). Trends in causes of mortality over quests, Ponce became governor of Leon looked over the far horizon for Puerto Rico in the early 1500s. Later, simple cures for death. In the scien- time made it seem that the survivor- faced with age and the fading of his tific age we seek our dreams on the ship curve was becoming “squared,” glory days, he heard of crystal waters, inner horizon of our genome, and approaching a limit—the MLP—that among trees bearing golden fruit we’re in an age when we can stop hy- the rapid acceleration of mortality tended by lovely maidens, that be- pothesizing about aging-related genes rates with age make it impossible to stowed eternal youth upon those who and, if they exist (unlike the Fountain survive. The reason for the illusion, bathed in them. Who could resist? Af- of Youth), find them. But before see- which was widely accepted by the bio- ter searching in vain in the Bahamas, ing what is now known about such medical aging research community in 1512 Ponce followed magnolia- genes, we first need to consider just until quite recently, was that early ex- scented offshore breezes to what he what kind of phenomenon aging actu- trinsic causes of mortality like infec- hence named “Florida,” where his ally is. tion were being reduced by public search also failed—but he would re- health measures. If we could finally turn. remove those causes we would have In longing for long life, Ponce de WHAT KIND OF EVOLUTIONARY something rather squarish (curve C), because the remaining intrinsic aging PHENOMENON IS “AGING”? processes would then predominate. The fitness associated with any trait However, the MLP was far beyond Kenneth Weiss is Evan Pugh Professor of is a life-history phenomenon. Age-spe- ages most people ever attained, so it Anthropology and Genetics, at Penn Uni- was always difficult for evolutionary versity. cific timing of reproductive maturity, fertility, and mortality determine life- biologists to accept the notion, in part time reproductive success. Life-his- also because one of its rather incredi- © 2004 Wiley-Liss, Inc. tory traits are complex, because they ble implications was that the known DOI 10.1002/evan.20008 Published online in Wiley InterScience can be affected by selection and drift causes of death were biologically un- (www.interscience.wiley.com). directly, but even traits like locomo- related to the determination of life- CROTCHETS & QUIDDITIES Ponce de Leon 83 Why would the idea that aging is a unified biological trait, or that there could be a simple genetic MLP-direct- ing switch, seem plausible in the first place? One oft-cited reason is that among vertebrate species there is a systematic relationship between esti- mated lifespan and measures like mean body or brain size (Figure 3). Indeed, the same age-patterns of dis- eases that fail to support the notion of a fixed MLP to kill us, suggest that there must be some common underly- ing processes that evolution (or we) might play with to preserve us. At any given age, the absolute risk of death from different causes varies by orders of magnitude. But the change in those risks with age are very similar (Figure 4); diverse causes rise in risk at roughly the 5th power of age. Similar diseases strike mice, mon- Figure 2. A survivorship history, in percent surviving from birth each succeeding age. keys, and men, who share largely the General pattern of U.S. mortality by age in 1900, 1950, and (curve C) the continuation of same genome, yet are scaled to each that trend giving the appearance of a squared survivorship curve at the hypothetical species’ lifespan, indicating that evo- human MLP. Curve D shows an “extended” life history without the squaring, as has been seen in recent years, leading to the suggestion that human life can be indefinitely ex- lution may somehow calibrate the tended. Schematic. overall rate of aging, rather than spe- cifically of death. The tapering off of span, and without them we could all live in good health until our MLPth birthday.2 Aging research might not make us immortal, but we’d at least be able to have a well-planned Last Sup- per. Instead, and more plausibly, recent mortality data show that death rates do not rapidly accelerate at very old ages (Figure 2, “extended” curve D). This means that the oldest old do not drop off suddenly, but gradually: there is no “squaring” of survivorship. The MLP vanishes—and the unrepen- tant research lobby now touts its new insight that human life can be ex- tended indefinitely. But this too is a Leonid dream. Life expectancy and health at older ages have recently in- creased, in part because of life-extend- ing intervention like less physical stress, better nutrition, drugs and vac- cines, bypass surgery, cancer chemo- therapy, bronchial ventilators, more effective long-term and emergency room care, and the like. But a visit to a senior center reveals the sobering truth that old people are “old” in roughly the same complexity of ways Figure 3. Age and lifespan: something’s going on here. Relationship between body size and as always. estimated lifespan among vertebrate species. 84 Weiss CROTCHETS & QUIDDITIES Figure 4. Different causes of death vary greatly in absolute risk but share similar patterns of acceleration with age. Risk is on a log scale. 1999–2001 U.S. mortality.3 some causes seen here reflects the sec- would seem obvious that the rest of natural selection. But wearing out ular trends (curve D) in Figure 3 and our cells, with the same genome, don’t does not explain our long post-repro- is due, at least in part, to the differen- have to wear out either. To bowdlerize ductive persistence, and a variety of tial loss with age of individuals genet- James Hutton, a founder of modern theories and controversies, have been ically susceptible to the various dis- geology, all life today is composed of advanced for that, some in the context eases. Thus, those who survive cell lineages that are about 3–4 billion of the broader evolution of primate represent their own longevity, but not years old, with “some vestige of a be- life-histories.4–7 that of people generally. ginning—no prospect of an end.” Evolutionary explanations almost If these data reflect an underlying always rest on the assumption that if aging process, that might account for aging is highly organized it must have another curious aspect of Figure 3, WHAT IS THE LIKELY been molded by selective forces, and that suggests that humans live longer, EVOLUTIONARY EFFECT ON the genes involved are routinely hy- by an amount roughly equaling the AGING-RELATED GENES? pothesized (“Suppose a mutation in- length of our post-reproductive sur- Everything here seems to cut both creases lifespan;...”). I think this vival, than a mammal our size has any ways. Does evolution kill us off or view of life is overdone, but it is worth right to expect. Although this could keep us going? One general theory for considering the likely resulting im- just be an artifact of multiple causes, the evolution of senescence is that pact of those forces, whatever they the possibility of a common underly- nothing evolved specifically to kill us are. ing cause understandably raises the off, but that the price of genes that First, however, we should not over- hope for a Gene Therapy of Youth. give us plenty at twenty is to become interpret statistical data, especially Immortality! What in the Devil’s weighty at eighty. This is known as with a measure like lifespan. A spe- Dictionary Ambrose Bierce quipped negative pleiotropy, and the idea is that cies-specific lifespan or MLP is the ex- that people would apply on their genes selected for early fitness can tremum of a population phenomenon, knees and be eternally proud to die have deleterious effects in later life, whose estimation depends on sample for, is clearly possible at the cell level.