A Means to an End: The Biological Basis of Aging and Death (review)

A Means to an End: The Biological Basis of Aging and Death, by William R. Clark. New York, NY: Oxford University Press. 1999. 234 pp. $27.50.

A Means to an End represents William R. Clark's fifth published volume and his second on senescence and life span. Having just read Clark's 1996 contribution, Sex and the Origins of Death, and finding it a good read, I was pleased to review his latest work. Clark's background as a cell biologist, physician, and immunologist have well prepared him to examine the biological basis of senescence, and his lucid writing style provides a volume that is easy to read and absorb. In both volumes Clark writes in terms accessible to a general reader and the informed public (explicitly stated in the news release that accompanied publication of this volume). There are no formal references within the text itself, although there are a few footnotes scattered about in its 11 chapters and a summary bibliography for each chapter at the end of the volume. When necessary, Clark alludes to the work of such notable gerontologists as Hayflick, Carry, Rose, Williams, and Finch by name, but generally without citing any specific publication. Although the research scientist may find this a bit disconcerting, as I did when he glossed over still-debated theoretical points, it does allow the general reader to skip along with Clark as he covers a broad array of background material in the molecular and evolutionary biology of senescence. Unfortunately, as Clark promotes his own particular views on the evolution of senescence--"that ultimately all of them (various forms of natural death) involve information embedded in and controlled through our DNA" and that "senescence is nature's backup plan," . . . "so senescence and compulsory death . . . did have to be selected and fixed as stable traits in those species in which they evolved"--those without a background knowledge of theoretical developments in senescence research may walk away with the opinion that much more has been settled than actually has.

Clark begins by examining aging, senescence, and life span across species and over human evolution and suggests that species-specific maximum life spans not only are a reality of evolution, but that they are governed in part by how long after birth senescence must be delayed to permit replacement level reproduction and by metabolic processes within each species, "being determined solely by the rate and timing of the onset of senescence" (italics in original). Other work, for example Williams (1957), Kirkwood and Holiday (1979), Michael Rose (1991), Finch and Rose (1995), emphasizes an evolutionary model whereby senescence is never actively selected for but rather results due to the inability of natural selection to act beyond the period of maximum reproductive potential. Therefore, no genetically determined maximum life span exists for species, rather the maximum observed life span is due to stochastic processes. Throughout this volume Clark critiques such evolutionary models. In the next chapter, Clark presents a model of how the senescent deaths of individual cells, the Hayflick limit to replication of fibroblasts in vitro, and a limited number of fundamental processes are what determine senescence in whole organisms. In Clark's model, "senescence is the sequence of events (that convert) . . . a metabolically active cell, through a series of genetically controlled events, to a cell no longer capable of metabolic function." That is, "senescence and compulsory death did appear at a specific point in evolution, and they did have to be selected and fixed as stable (genetic) traits in those species in which they evolved."

In Chapter 3, "The Evolution of Senescence and Death," Clark sets out to answer what he sees as the fundamental question in gerontology, "But where did the genes responsible for aging come from?" Clark observes, as have others including evolutionary biologists, that the "balance between damage and repair of DNA is one of the most important aspects of cellular senescence...