Chance, Development, and Aging (review)

Chance, Development, and Aging, by Caleb E. Finch and Thomas B.L. Kirkwood. New York, NY, and Oxford, UK: Oxford University Press. 2000. 278 pp.

This is an ambitious work that attempts to address a longstanding question in the biology of aging: Why do genetically uniform individuals exhibit such wide variations in their patterns of aging? The authors suggest that the classical answer, variation in the environment, is not sufficient to explain differences in longevity between genetically identical human twins or inbred laboratory strains. Instead, they propose that chance events, particularly those that are manifested during prenatal development, play major roles in determining individual outcomes. They further suggest that the explanation of individual patterns of aging must take into account subtle mechanisms such as extensive chance variations in cell number and connections, in cell fates during differentiation, and in physiological patterns that arise during development. All of these may have profound impacts for what patterns of aging we might expect to observe in any specific species.

Thus, the authors propose that it will be fruitful to examine various limits to genomic authority in life history that arise through the actions of chance. In doing so they do not challenge the importance of genes in determining life histories, but instead propose that there is considerable evidence that developmental noise has significance in determining life history outcomes. The authors accept the idea that geneticists have recognized the role of chance in evolutionary genetics, particularly in producing mutations. Finch and Kirkwood further recognize that evolutionary theory in general adequately explains the patterns of senescence that we observe in living things. However, the point of their work is to highlight the less recognized role of chance at higher levels of organization such as in cells, organs, individuals, and entire populations. Finch and Kirkwood therefore emphasize the need for the development of a theoretical framework for understanding how chance fluctuations in developmental processes have major consequences for the life histories of individuals. This is contrasted to cases were these consequences may be tightly constrained by genetic controls. For example, the wide individual variation of life spans in laboratory reared Caenorhabtitis elegans needs to be explained, as well as the tightly controlled emergence of organisms such as the periodical cicadas (Magicada).

To their credit, the authors carefully explain what they mean by chance in chapter 1. Chance is the generic term that describes the generating force behind variations that cannot as yet be explained. The terms random and stochastic are forms of chance. Random describes events whose outcomes are not predictable, while stochastic is meant to describe a distribution of outcomes. These stochastic outcomes contain elements of randomness. Finally, they also include chaotic functions as providers of randomness in biological processes. Chaos arises from completely deterministic nonlinear functions, often when different physical systems are weakly connected. Initial conditions are crucial in determining the trajectories of chaotic functions. It is here that their suggestion of chance fluctuations in developmental processes having major consequences for the life histories of individuals may be most fruitful. For if a particular developmental process is described by functions that are nonlinear and is weakly connected to other such developmental processes, then we would expect wide variation in outcome. In fact, we would also expect that natural selection would act on these connections, either more tightly constraining them through time, or allowing them to fluctuate. Processes that were more closely linked to fitness would be more likely constrained by natural selection, while those weakly linked, as might be expected in many processes manifesting themselves in later age, would be more loosely coupled. The balance of these types of chance interactions could have profound influence on how individuals age.

Finch and Kirkwood marshal an impressive amount of evidence to support their central contention. For example, in chapter 2 they describe how chance developmental events affecting cell numbers in the reproductive system can modify individual patterns of aging. In chapters 3 and 4 they consider the mechanisms of cell number variation more generally...