Abstract
This monograph covers the current research on the molecular aspects of aging and the genomic aspects of many of the important metabolic diseases and the major organ system diseases associated with senescence, morbidity and mortality in many organisms including primates and humans. At first glance one might expect this book to be directed to gerontologists and molecular biologists, but the content shows this to be a very readable set of reviews for comparative pathologists with both academic and industrial career interests. With the current interest in new therapeutic targets for management of obesity (MCHR-1, ghrelin antagonists, etc.), diabetes (GLP-1 analogs, glucokinase activators, DPP IV inhibitors, Sirt 1, Sirt 2 enhancement, etc.), mitochondrial dysfunction, cardiovascular diseases and many cancers in mind, the editors have assembled an timely series of reviews written by some of the most productive and thoughtful scientists currently working in this field. This book was published early in 2008 and many of the references were published in 2007, a real effort to keep the text current and timely.
The topics reviewed consider the causes of senescence and current strategies that might delay this relentless process. It covers the molecular genetics of aging, the many genes that are involved in the regulation of aging, the interactive non-genomic causes of aging, the evolutionary theories of aging, and the complex relationship between diet and aging. There are chapters on specific aging model systems including stem cells, yeast, nematodes, Drosophila, small rodents, primates and the comparative aspects of these models that apply to humans. Among the specific topics covered is the current understanding of the mechanisms operating in oxidative stress, mitochondrial dysfunction, caloric restriction, sirturins, telomeres, DNA repair, neuroendocrine systems, and the gene networks involved in aging and cancer development. In addition, this monograph includes a balanced discussion of the potential of these molecular mechanisms to lead to the development of new drugs and changes in our approach to therapeutics to regulate aging and ameliorate age-related diseases, such as diabetes, cardiovascular diseases, Alzheimer's disease and various forms of cancer.
This book is well organized and referenced. The editors and authors have made a good effort to be clear and current, without using reductionist oversimplification of the many complex and interactive aging processes. For example, the chapter on aging gene networks notes that no less than 447 age-related genes have been identified in human kidneys with transcriptional profiles that correlate with physiological and morphological changes in aging patients. Similar complex genomic patterns have been observed across diverse species from yeast to mice to primates in response to caloric restriction, and in the more complex organisms these aging changes vary among organs depending on metabolism and function. In addition to genomic DNA, aging mitochondrial DNA and metabolism change in complex ways that reflect human and animal adaptation to their ancient evolution, migrations, climatic, and nutritional environments. This book demonstrates that our understanding of aging is rapidly evolving from complex biomarker analysis to an understanding of the genomic and environmental basis of life on earth. The editors and authors have served us with an intellectual feast of current knowledge in thoughtfully measured portions. A veterinary pathologist will gain a useful understanding of the complexity of aging from this work. It is highly recommended.