Sci. Aging Knowl. Environ., 19 December 2001
Vol. 2001, Issue 12, p. vp9
[DOI: 10.1126/sageke.2001.12.vp9]


Can Current Evolutionary Theory Explain Experimental Data on Aging?

Joshua Mitteldorf

The author is affiliated with the Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA. E-mail: josh{at};2001/12/vp9

Key Words: evolution • group selection • natural selection

As Mitch Leslie has so lightly reminded us in "Aging Research Grows Up" (1), study of the evolution of aging is not without its controversy, but those who disagree with the orthodoxy are all wrong. These dissidents tend to be experimental geneticists, developmental biologists, complexity theorists, and others who are ignorant of the basic principles of evolutionary biology established 30 years ago (2).

Since that time, mainstream evolutionary theory has been committed to a paradigm of selection exclusively at the individual level. Aging entails a fitness cost to the individual, who has nevertheless acquired a network of genes that determines and regulates the rate of aging. So the prevailing theories of aging have been built on a presumption that aging has evolved as a side effect of genes that carry a fitness benefit for the individual. This benefit must be strong and universal to account for the universality of aging; hence there is wide agreement that genes that cause aging must enhance fertility.

But in the two generations since foundations were laid for the current evolutionary theories of senescence, new data have come to light that challenge the theories at their core. Today, the theories survive as a framework in which to interpret data, but their persistence might result from an absence of viable alternatives rather than because there is an excellent fit with experimental results. It might be appropriate to consider whether the data demand of us a new paradigm. Recent developments in evolutionary theory point toward origins for this new paradigm.

What are the theoretical reasons for thinking that selection operates exclusively at the individual level? The reasons are cogent and are well argued in George Williams's classic, Adaptation and Natural Selection (2). The essence of the argument is that a prerequisite for group selection is the persistence and fixation of a mutation, arising originally in a single individual. But evolution at the individual level is rapid and direct, scaled by the lifetimes of individuals; evolution at the group level proceeds at a slower pace, scaled by the extinction time of populations. Hence it seems unlikely that any trait entailing even a small cost to the individual can persist long enough to test its effect on the fitness of the population as a whole.

What are some experimental challenges to the prevailing theories?

1) Aging genes and fertility. Over the past decade, single gene mutations have been discovered that extend life-span in nematodes (3), fruit flies (4), and mice (5). Because deletion of these genes causes the animal to live longer, it seems inescapable to characterize them as "aging genes." It is far from clear, however, that they offer any benefit to fertility. For example, the mouse gene p66shc affects apoptosis in damaged cells, which appears to be up-regulated to the point where healthy cells are routinely being killed in older individuals. Experiments show that this substantially shortens the mouse life-span, but it is hard to imagine what benefit it might carry for fertility.

2) Caloric restriction and aging. In calorically restricted (CR) rodents, the aging rate is slowed substantially, whereas the immune system is more effective and activity levels are enhanced (6). Where does the capacity come from to sustain this effort, and why does the body choose not to extend its life when fully fed? This phenomenon is a particular embarrassment to the reigning "disposable soma" theory of senescence, which holds that a tight caloric budget is the root cause of aging. Theorists have responded by emphasizing the large fertility cost entailed in the CR response (7), but experiments suggest that the life extension brought about by CR is independent of the effect on fertility (8): In male rodents, life-span is substantially extended with only modest curtailment of fertility; in females, life-span continues to lengthen as the severity of caloric restriction is increased (9). For example, with caloric restriction at >30%, a regime in which the females are already completely infertile, life-span continues to grow with severity of caloric restriction all the way down to the threshold of starvation, around 60%.

3) Conserved mechanisms of aging. Some mechanisms of aging appear to have been conserved over vast evolutionary time scales (10, 11). For example, evidence is emerging that implicates apoptosis as a senescence mechanism (12-16). Apoptosis has all the appearance of a deliberate adaptation, and hints that it plays a role in aging are problematic for the standard theories. Likewise, replicative senescence through telomere attrition is an independent, purposeful adaptation, and its implication in cellular senescence in the aging of higher organisms belies all theories of pleiotropy. If processes such as telomeric senescence and apoptosis, which we think of as purposeful adaptations, do turn out to play a central role in the aging of higher organisms, conventional theories of aging will face trouble: It would then be difficult to support the notion of aging as a side effect of processes that primarily enhance fertility, and impossible to maintain the idea that aging derives from a failure to allocate adequate resources to repair and maintenance functions.

What new theoretical developments might hint at an alternative framework?

1) Almost as old as the proscription on arguments from group selection is David Sloan Wilson's work on multilevel selection (MLS) theory (17, 18). In recent years, the body of literature on MLS has swelled, as has the number of recognized mechanisms by which group-level adaptations might emerge (19, 20).

2) Complexity theorists revel in the distinction between smooth analytical processes that closely track our intuitions and the surprising, chaotic realms of complex systems. There is now a community of artificial life specialists, who study evolution with computer models rather than differential equations. They shun the equations and theorems of population genetics, because these have been derived on the assumptions of infinite populations and negligible epistasis, conditions that are rarely achieved in nature. Most of the people in this community hail from backgrounds in physics or computer science rather than evolution and have little reverence for the distinction between individual and group selection. It is arguable that a complex systems approach makes group selection far more plausible than does an analytical approach (21).

3) The evolution of evolvability has been an intriguing field of study since the ground-breaking paper of Wagner and Altenberg (22). Evolvability advocates argue that the structure of chromosomes and the organization of the genome appear to be optimized in ways that promote the efficiency of evolutionary processes. But evolvability is a property of populations, not individuals. Evolvability itself can only evolve via a process of long-term selection on populations, which is exactly the kind of selection that traditional evolutionary theory warns us does not exist. And if evolvability has somehow evaded the theoretical ban on group selection, can senescence be viewed as a population trait that contributes to evolvability? Senescence contributes to the adaptability of a population by reducing the effective generation length and enhancing genetic diversity, as Weismann (23) pointed out over a century ago.

What's next? It's one thing to take pot shots at established evolutionary theory and quite another to put forward a viable alternative. It remains to be seen whether a plausible model of the evolution of senescence can be constructed on the basis of long-term and widely dispersed benefits of higher population turnover and increased genetic diversity.

December 19, 2001
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Citation: J. Mitteldorf, Can Current Evolutionary Theory Explain Experimental Data on Aging? Science's SAGE KE (19 December 2001),;2001/12/vp9

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