Means to an End: The Biological Basis of Aging and Death
by: William R. Clark
Topics include: senescence effector genes, senescence repressor genes, fully fed controls, underlying senescence, special function genes, overall senescence, maximum possible lifespan, specialty genes, calorically restricted diet, organismal senescence, accidental cell death, maximum lifespan, maximal lifespans, helicase gene, replicative senescence, average human lifespan, aging phenotypes, human senescence, senescent state, restricted mice, senescence program, human aging process, cellular senescence, younger cells, caloric restriction
From Publishers Weekly
A professor emeritus of immunology at UCLA, Clark here examines "the process of aging from a new and increasingly important perspective, that of cell and molecular biology and the underlying discipline of genetics." When addressing each of these biological subfields, Clark effortlessly takes readers from the simple to the complex, from a discussion of single-celled organisms to human beings. Along the way, he summarizes the latest scientific information while outlining prospects for future research. Although this is a scholarly book, not a how-to manual, Clark does discuss strategies for extending the average human life by caloric restriction (reductions of 20% to 25% seem to be required) and the use of antioxidants (natural forms found in fruits and vegetables appear to be much more effective than supplements). He also does a nice job of exploring the causes of Alzheimer's disease, various forms of cancer and an array of genetic disorders that afflict the young by making them age prematurely. Finally, in this neatly informative work, Clark uses a sociological and political perspective to probe the tensions likely to arise between length of life and quality of life as medical advances continue to accumulate, and to consider the broad ramifications inherent in an aging population. 21 linecuts.
Copyright 1999 Reed Business Information, Inc.
From Library Journal
As in his previous books, Clark (immunology, emeritus, UCLA; The New Healers: Molecular Medicine in the Twenty-First Century, LJ 12/97) does not hesitate to introduce the lay reader to complex concepts in cell and molecular biology. The news media and popular magazines tend to overestimate the impact of aging research on humans, but Clark looks at things realistically, especially the effects of reduced caloric intake and antioxidants at the cellular level. Clark concludes his book with an interesting discussion of the economic and social impact a longer lifespan might have on humans. Clark's is less anecdotal than some of the other aging books on the market: Steve Austad's Why We Age (Wiley, 1997), Leonard Hayflick and Robert Butler's How and Why We Age (Ballantine, 1994), and John J. Medina's The Clock of Ages (LJ 3/15/96). He sticks to the scientific research and refers to articles published in top-ranked, peer-reviewed scientific publications in his bibliography. Recommended for larger public libraries.AMargaret Henderson, Huntington, NY
Copyright 1999 Reed Business Information, Inc.
From Kirkus Reviews
A virtual textbook on what the growing knowledge of biochemistry, genetics, and molecular biology is revealing about the basic mechanisms of aging. Clark, professor emeritus of immunology at Univ. of Calif., Los Angeles, whose previous work, The New Healers: Molecular Medicine in the Twenty-First Century (1997), seriously challenged readers not trained in these sciences, has returned to the classroom for yet another dense lecture, complete with graphs, tables, and diagrams. With technical expertise, he describes in detail how the process of aging, or senescence, takes place at the level of individual cells and what is known about the internal regulation of that process by our genes. He relates how research into various genetic disorders that mimic the human aging process, such as Hutchinson-Gilford progeria and Werner's syndrome, is providing clues to the involvement of genes in the aging process; and he dismisses claims that rejuvenation or immortality can be achieved through the manipulation of telomeres, those segments of DNA at the tip ends of chromosomes that have been called the cell's internal timekeepers. The effects of caloric restriction on lifespan are considered, as is the role of antioxidants in reducing the risk of deadly cancers and cardiovascular disease. What is clear from Clark's text is that more is known about how and why we age than has ever been known before, and that with the coming completion of the Human Genome Project, knowledge of the genes involved in aging will greatly expand. In his final chapter, which is the book's least technical and most thought-provoking, Clark considers briefly what the impact on society will be as that knowledge is applied and leads to a longer, healthier average human lifespan. A scientist's careful, unsensational account of the current status of research into aging that requires from the reader a level of commitment well beyond mere curiosity. -- Copyright 1999, Kirkus Associates, LP. All rights reserved.
American Scientist, September/October 1999
There is a real need for books that can educate the public about complex biological processes and present the promise of modern aging research with all the hope that drives contemporary gerontologists-and with all the caveats and unknowns that temper their optimism. In this respect, A Means to an End is largely a success. Much to his credit, the author does not shy away from biological complexity. he clearly and ocncisely explains basic facts and concepts so that complexities can be understood and appreciated.
Reviews:
The case for programmed senescence:
Professor Clark writes with elegance and employs a reasoned tone, but he is not always direct, and often expresses ideas in the understandably tentative way of a very exacting scientist. Consequently it is not easy to see that nowhere in this book does he directly say what causes aging and death. Nor does he simply say we don't know. What he does say is there are some persuasive theories, especially the evolutionary model began by Haldane and Medawar and refined by George Williams (pp. 49-50), that are consistent with the data that "may be essentially correct, at least in broad outline." (p. 52). Clark makes it clear that we have senescence effector genes in our cells but he doesn't say how they got there, only that they were "already in place in the earliest eukaryotic organisms such as paramecia and yeast." (p. 57) The reader is left to believe that there is a mechanism that retains them, but what that mechanism might be is unclear.
I am led to believe that senescence is built into our cells and is part of our genetic makeup. We are programmed to grow old and die. Just how is what Professor Clark is exploring here. He concentrates on the cellular level because it is his belief that this is where the mechanisms for senescence can be found. On page 190 he argues that senescence is genetically controlled and not the result of a random breakdown, citing the fact that "maximum lifespan is species-specific." In short, humans live a lot longer than dogs, contrary to what might be expected if senescence were caused by cells getting old and wearing out. He points out on page 48 that "mice and humans, although composed of proteins that are extremely similar at a chemical level, have both average and maximal lifespans differing by a factor of 30 or more."
Clark also covers in some detail such issues as the evolution of senescence, average and maximum lifespan; genetic diseases such as Werner's syndrome, the Hutchinson-Gilford syndrome and others; oxidative stress as a cause of cellular senescence and the use of Vitamin E and other antioxidants; the aging brain and Alzheimer's disease; cancer and the social and economic effect of humans living longer. A chapter is devoted to the phenomenon of increased lifespan through restricted caloric intake.
This is an authoritative and persuasive book, well written and well presented.
Excellent review of aging research for the general public:
This is a very clearly written, basic book on aging research that is up-to-date. It covers the history of aging research, with particular emphasis on Hayflick's demonstraction of replicative senesence, and gives a fascinating speculation regarding the origin of the aging process in eukaryotic cells as a consequence of sex. Despite this, I really think this is a non-technical book, as he takes time to explain even the most basic of basics, like how nucleotides make up DNA.
Easy to read book. After lengthy introduction author concentrates on the research about genes that suppress the cell senescence and control. Discussion about cancer cells where cell division is not checked. Final chapters discusses the effects of oxidants, obesity, low calorie diet or similar things where eventually a claim comes that beside the gene control everything else does not amount more than %15 in total effect. So unless we control the genes we will soon or later die.
Dr. Clark provides a good review of the field but fails, in my opinion, to provide a clear explanation for "The biological basis of aging and death". The theories of the evolutionary biology of aging clearly argue that "aging" cannot be "genetically programmed" or that "We are programmed to grow old and die" as other reviewers have concluded from reading this work. That points out the weakness in this book -- a failure to clearly differentiate between senescence, aging and death. There are two primary theories for why we age -- "the declining force of natural selection" (i.e. it is difficult to optimize a genetic program to produce non-aging organisms) and "antagonistic plieotropy" (i.e. the genetic program is optimized for reproduction at the expense of non-aging longevity). Dr. Clark seems to suggest that the genetic program for senescence is what causes aging and death. In fact the genetic program for senescence is largely an anti-cancer program. It may as a side effect contribute to aging and eventually death but its primary purpose is to prevent cancer. There is a very big difference between saying that aging and death result from an "incomplete" program and saying that aging and death result from a pre-programmed senescence program. One of my primary criticisms is Dr. Clark's pseudo-deathist philosophy. The tone of the book seems to suggest that aging is pre-programmed and cannot be changed. He says, on pg 218, "Will we want to go this far in our search for the fountain of youth? It is unlikely even to be proposed in the lifetime of anyone reading this book, but it is not at all beyond the realm of possibility." (He is speaking of the application of gene therapies to lifespan extension.) I have been proposing such methods for lifespan extension for most of the past decade and have conducted research and founded companies to forward these goals. The human genome is a program. It has bugs in it that result in aging. We can comprehend those bugs and apply patches to fix them allowing the extension of human longevity to the accident-rate limits which will be thousands of years. Individuals who really want to understand aging should read books by people who have studied the field for many years. The best authors, in my opinion, would be Steve Austad, Tom Kirkwood and Caleb Finch. While many of their works may be older than this book, they have a greater depth of understanding of the subtleties of the study of aging that this book fails to discuss.Yes, death is genetically programmed
This book embraces a rational and well explained journey in the field of aging. Here I read for the first time strong statements about the programmed nature death, that is present since fertilization. We learn the basic experiments that support Haldane theory about sex and aging and we appreaciate the beatiful connection between replicative senescence and species-specifc mortality. The book is clear and well readible and I strongly recommend it to science and non-science crowd.