A Means to an End — The Biological Basis of Ageing and Death.

William R. Clark. Oxford University Press, New York. 1999. Pp. 234. Price £18.99, hardback. ISBN 0 19 512593 2.

When asked, many of us would want to live for a long time, if not happily ever after. Unfortunately, death, the inevitable end of the ageing process, will come to us all. This book considers the biological basis of ageing and death, both by reviewing what we know about the ageing process at present, and looking ahead to what might be uncovered in the future. Although the ageing-related phenomena are approached from an evolutionary perspective, this is only loosely done throughout the book. Clearly, its main focus is the proximate causes of ageing: how do the age-related changes occur in organisms and how are they regulated. In my opinion, this sets the book apart from other books on the subject, both from the more evolutionary and more medically orientated treatments. As a consequence, this makes the book valuable for all those interested in ageing and age-related processes.

After clearly defining ageing, mortality and longevity and how they relate with each other, Clark makes the important point that what matters is separating the causes from the consequences of ageing. Moreover, the distinction is made between ageing and non-ageing deaths and how ageing has increasingly become significant in the human population because environmental causes of death, such as poor medical care and hygienic conditions, have been removed in modern, developed societies. He then discusses the issue of replicative senescence in cells, and makes the argument that we need to study ageing on this level in order to understand the process at an organismal level. However, programmed cell death, for example during development, is in many cases unrelated to whole organismal ageing. Here, Clark fails to discuss levels of control and levels of natural selection. Cell proliferation in the body needs to be controlled in order for the whole organism to be reproductively successful.

Clark then deals with the developmental genetics of ageing and argues that the non-ageing state of cells is lost during development as differentiation progresses. He subsequently brings up the notion of senescence effector, and senescence repressor genes. This, to me, is the only major flaw of this book, especially as he puts this in an evolutionary context. The repressor and effector genes are what Clark calls housekeeping genes; genes with an essential function in the cells that have been highly conserved between species (from worms to man). Of course, the first problem then is that these genes have not been selected for in the course of evolution as programmed ageing mechanisms, but to ensure regulated and controlled development and organismal functions. Secondly, this implies group selection for which, it has been shown, there is a very limited (if any) role in nature. On the basis of the conserved nature of the housekeeping genes and mutations with large effect, such as those involved in progeriatic diseases and the cell cycle, he concludes that ageing is underpinned by relatively few genes instead of the many that are suggested by evolutionary theories. In general, the evolutionary theories are rather hard done by in this book, in the sense that their full and still evolving argumentation and supporting data are not given enough prominence. As shown here, this leads to some serious simplifications and/or misinterpretation that will cause confusion. All of the data Clark presents can be reconciled with current evolutionary theories. The book discusses in considerable detail the genetics underlying human accelerated ageing, cancer, cell cycling, oxidative damage and DNA repair and their relationship with ageing. There is an excellent chapter on caloric restriction and how this all ties in with what is known about the mechanisms underlying ageing.

The book ends with a brave chapter on the future and what the potential is for (further) increasing human average and maximum life span. Clark rightfully argues that extending human life may well be a mixed blessing if it were not accompanied by an increase in the quality of human life at advanced ages. Moreover, there will lie many social and economic problems ahead if our societies remain as they are now. Here Clark is as optimistic in tone as he is in the rest of the book, and believes that our societies will change. He takes no notice of the social injustice that is imbedded in our societies at present and that only a limited number of us will benefit from extended life (bluntly, those who can afford it). Moreover, many of the social security systems in the developed world are being changed, but few will argue that this change will at all close the gap between rich and poor. I fear that given the way our free-economy-driven societies work, the biggest constraint on the quantity and quality of human life may well be the ‘End to the Means’.

In summary, the book uses communicable and thought provoking language, good and original metaphors and is generally solidly built on scientific observations. This makes it, both from the biological and the sociological perspectives, a very good read.