Cover image for Chance, development, and aging
Title:
Chance, development, and aging
Author:
Finch, Caleb, 1939-
Personal Author:
Publication Information:
New York : Oxford University Press, 2000.
Physical Description:
x, 278 pages : illustrations ; 24 cm
Language:
English
Added Author:
ISBN:
9780195133615
Format :
Book

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Library
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Material Type
Home Location
Status
Central Library QP86 .F526 2000 Adult Non-Fiction Central Closed Stacks
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Summary

Summary

In Chance, Development, and Aging, two leading biological gerontologists review and evaluate all of the available data to elucidate the respective roles played by genes and chance developmental events in determining the course of aging in individuals. The combination of genetic and externalenvironmental influences provides only an incomplete answer. Inbred laboratory animals, for example, exhibit a wide range of life spans despite having nearly identical genes and environments. Similarly, uncovering the genetic risks for Alzheimer's disease has not enabled doctors to predict withconfidence its onset and severity. This book argues that understanding chance events, specifically random variations during prenatal development, is essential for answering these questions. The book draws on the extensive research in developmental biology on random variations in form and function,while putting this research in a new context. The discussion sheds light on a range of questions, from understanding menopause to explaining why identical twins are not truly identical. The book will be invaluable for gerontologists, geneticists, developmental and reproductive biologists,physiologists, and a broad range of physicians and investigators in experimental medicine.


Author Notes

Caleb E. Finch is ARCO and William Kieschnick Professor of Neurogerontology at the University of Southern California and Director of the USC Alzheimer Research Center.


Table of Contents

1. Chance and Its Outcomes in Agingp. 3
1.1. Main issuesp. 11
1.2. Life span variationsp. 14
1.3. Variation in reproductive agingp. 19
1.4. Variable numbers of irreplaceable cellsp. 23
1.4.1. Ovarian oocytesp. 25
1.4.2. Neuron numbersp. 28
1.4.3. Variations of neuron structures in genetically identical individualsp. 38
1.4.4. Neuron numbers and the threshold for dysfunctionsp. 39
1.5. Variations within an individualp. 42
1.5.1. The lateral line systemp. 42
1.5.2. Asymmetry of brain regionsp. 43
1.5.3. Asymmetry and its fluctuationsp. 48
1.6. Variations in molecular controlsp. 54
1.6.1. Pattern formation and the suppression of errorsp. 54
1.6.2. Control of gene expressionp. 58
1.7. Limits to genomic specificationp. 65
1.7.1. Programmed versus stochastic agingp. 65
1.7.2. Errors in gene expressionp. 69
1.7.3. Genes, evolution, and agingp. 73
1.8. Synopsis of the argumentp. 75
2. Chance and Reproductive Agingp. 76
2.1. The mammalian ovaryp. 76
2.2. Oocyte numbers determine menopausep. 83
2.3. Development and ovarian oocyte variationsp. 86
2.4. Maternal age factors in birth defectsp. 91
2.5. Health risks associated with menopausep. 94
2.6. Fetal steroid variations and reproductive system developmentp. 98
2.6.1. Brainp. 98
2.6.2. Prostate and benign prostatic hyperplasiap. 103
2.7. Prezygotic phenomenap. 108
2.8. Conclusionsp. 110
3. Chance, Cell Fate, and Clonalityp. 111
3.1. Stochastic aspects of cell fatep. 111
3.1.1. Asymmetric cell divisionp. 111
3.1.2. Cell migrationp. 116
3.1.3. Cell deathp. 117
3.2. Stochastic aspects of cell clonesp. 120
3.2.1. Dispersion of neurons during cortical developmentp. 120
3.2.2. A repeated neuron structure: the lateral line system of frogsp. 125
3.2.3. Chance and clonality in intestinal cryptsp. 131
3.2.4. Hematopoiesisp. 137
3.2.5. Colony size variation in cell culturesp. 142
3.3. Somatic genome instabilityp. 146
3.4. Clonal attenuation, cell immortalization, and cancerp. 150
3.5. Conclusionsp. 155
4. Chance in the Developmental Environmentp. 157
4.1. Fetal interactionsp. 158
4.1.1. Rodentsp. 158
4.1.2. Humansp. 165
4.1.3. Evolutionary questionsp. 170
4.2. Environmental estrogensp. 172
4.3. Stress and effects on the nervous systemp. 174
4.3.1. During pregnancyp. 175
4.3.2. Neonatal handling and later neuron lossp. 176
4.4. Nutrition during pregnancyp. 181
4.5. Conclusionsp. 185
5. Limits of Determinism in Agingp. 186
5.1 Recapitulation and synthesisp. 186
5.2. Genetic predictions and their limitationsp. 196
5.3. Research agendap. 205
5.3.1. Attending to the noisep. 205
5.3.2. Need for a mathematical frameworkp. 206
5.3.3. Applications to medicinep. 209
5.4. Next steps toward a biology of aging and the individualp. 210
Referencesp. 212
Subject Indexp. 259
Author Indexp. 268

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