Sell / Lorenzini / Brown-Borg Life-Span Extension

Single-Cell Organisms to Man
1. Auflage 2009
ISBN: 978-1-60327-507-1
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 203 Seiten

Reihe: Aging Medicine

In recent years, remarkable discoveries have been made concerning the underlying mechanisms of aging. In Life-Span Extension: Single-Cell Organisms to Man, the editors bring together a range of illuminating perspectives from researchers investigating the aging process in a variety of species. This novel work addresses the aging process in species ranging from yeast to man and, among other subjects, features detailed discussions of the naked mole-rat, an exceptionally long-lived rodent; the relationship between dietary factors/food restriction and aging; and an evolutionary view of the human aging process. Single mutations that extend life span have been identified in yeast, worms, flies, and mice, whereas studies in humans have identified potentially important markers for successful aging. At the same time, it has been discovered that the genes and pathways identified in these studies involve a surprisingly small set of conserved functions, most of which have been the focus of aging research for some time. For example, the mTOR pathway, a regulator of translation and protein synthesis, has been identified as a common longevity pathway in yeast and Caenorhabditis elegans. In mammals, this pathway intersects with neuroendocrine pathways and with the insulin/insulin-like growth factor pathways, which have been identified as major modulators of life span and aging in both invertebrates and mice. Novel, emerging technologies and the increasingly wide variety of systems that are now used to study aging and the mechanisms of aging provide enormous opportunities for the identification of common pathways that modulate longevity. It is these common pathways that are the focus of this important volume.  

Autoren/Hrsg.

Sell, Christian

Lorenzini, Antonello

Brown-Borg, Holly M.

Inhaltsverzeichnis

1;Sell_Ch01_O.pdf;1
1.1;Sell_Ch01_O.pdf;1
1.1.1;Chapter 1;17
1.1.1.1;Reprogramming Cell Survival and Longevity: The Role of Tor, Sch9, Ras, and Sir2;17
1.1.1.1.1;1.1 Introduction;17
1.1.1.1.2;1.2 The S. cerevisiae Chronological Life Span;18
1.1.1.1.3;1.3 High-Metabolism Survival in Synthetic Dextrose Complete Medium;19
1.1.1.1.4;1.4 Severe Calorie Restriction: Survival in Water;21
1.1.1.1.5;1.5 Yeast Replicative Life Span;21
1.1.1.1.6;1.6 Evolutionarily Conserved Proaging Pathways;22
1.1.1.1.7;1.7 The Genetics of Chronological Aging: Reprogramming Stress Resistance and Cell Survival;22
1.1.1.1.8;1.8 Sir2 and Yeast Chronological Aging;25
1.1.1.1.9;1.9 Evolutionary Conserved Proaging Pathways;26
1.1.1.1.10;1.10 Conclusions;28
1.1.1.2;References;28
2;Sell_Ch02_O.pdf;1
2.1;Chapter 2;34
2.1.1;Common Aging Mechanisms: Energy Metabolism and Longevity in Caenorhabditis elegans;34
2.1.1.1;2.1 Introduction;35
2.1.1.2;2.2 The Insulin Signaling Pathway;35
2.1.1.3;2.3 Caloric Restriction;38
2.1.1.4;2.4 Mitochondrial Dynamics;39
2.1.1.5;2.5 Conclusions;41
2.1.2;References;42
3;Sell_Ch03_O.pdf;1
3.1;Chapter 3;46
3.1.1;Conserved Mechanisms of Life-Span Regulation and Extension in Caenorhabditis elegans;46
3.1.1.1;3.1 Caenorhabditis elegans as a Discovery Engine;47
3.1.1.2;3.2 The Major Axes of Life-Span Regulation in C. elegans;47
3.1.1.2.1;3.2.1 The Genetics of Aging;48
3.1.1.2.2;3.2.2 Endocrine Signaling;49
3.1.1.2.2.1;3.2.2.1 Insulin-Like Signaling;50
3.1.1.2.2.2;3.2.2.2 Transforming Growth Factor-b-Like Signaling;52
3.1.1.2.2.3;3.2.2.3 Tissue Specificity of Endocrine Signaling;53
3.1.1.2.2.4;3.2.2.4 C. elegans Insulin Signaling and Human Disease;54
3.1.1.2.3;3.2.3 Reproduction;54
3.1.1.2.4;3.2.4 Dietary Restriction;55
3.1.1.2.5;3.2.5 Mitochondria;57
3.1.1.3;3.3 Next Generation Studies to Identify Life-Span Regulators;58
3.1.1.3.1;3.3.1 RNA Interference;58
3.1.1.3.1.1;3.3.1.1 RNAi Screens for Increased Life-Span Phenotypes;59
3.1.1.3.1.2;3.3.1.2 Specialized RNAi Screens for Life-Span Phenotypes;60
3.1.1.3.2;3.3.2 Chemical Screens;62
3.1.2;References;63
4;Sell_Ch04_O.pdf;1
4.1;Chapter 4;71
4.1.1;The Genetic Architecture of Longevity;71
4.1.1.1;4.1 The Three Types of Longevity Responses;72
4.1.1.2;4.2 The Three Phases of the Life Span;76
4.1.1.2.1;4.2.1 The Developmental Span;76
4.1.1.2.2;4.2.2 The Health Span;76
4.1.1.2.3;4.2.3 The Senescent Span;78
4.1.1.3;4.3 The Genetic Architecture of Longevity;82
4.1.2;References;84
5;Sell_Ch05_O.pdf;1
5.1;Chapter 5;86
5.1.1;Mild Stress and Life Extension in Drosophila melanogaster;86
5.1.1.1;5.1 Introduction;86
5.1.1.2;5.2 Hypergravity;87
5.1.1.2.1;5.2.1 Hypergravity Increases Longevity of Males;87
5.1.1.2.2;5.2.2 Hypergravity Can Delay Behavioral Aging;89
5.1.1.2.3;5.2.3 Hypergravity Increases Resistance to Heat But Not to Other Stresses;89
5.1.1.3;5.3 Heat;91
5.1.1.3.1;5.3.1 Heat Can Slightly Increase Longevity;91
5.1.1.3.2;5.3.2 Heat Does Not Clearly Delay Behavioral Aging;91
5.1.1.3.3;5.3.3 Heat Increases Resistance to Some Stresses;92
5.1.1.4;5.4 Cold;92
5.1.1.4.1;5.4.1 Cold Increases Longevity;92
5.1.1.4.2;5.4.2 Cold Can Delay Behavioral Aging;92
5.1.1.4.3;5.4.3 Cold Increases Resistance to Some Stresses;92
5.1.1.5;5.5 Irradiation;94
5.1.1.5.1;5.5.1 Irradiation at the Egg Stage Increases Longevity;94
5.1.1.5.2;5.5.2 Can Irradiation Delay Behavioral Aging?;94
5.1.1.5.3;5.5.3 Irradiation Decreases Resistance to Heat and Desiccation;95
5.1.1.6;5.6 What Are the Causes of Hormesis?;96
5.1.1.7;5.7 Conclusions;97
5.1.2;References;98
6;Sell_Ch06_O.pdf;1
6.1;Chapter 6;101
6.1.1;Global Food Restriction;101
6.1.1.1;6.1 Overview;102
6.1.1.1.1;6.1.1 Life Extension;102
6.1.1.1.2;6.1.2 Retardation of Physiological Deterioration;103
6.1.1.1.3;6.1.3 Retardation of Age-Associated Diseases;103
6.1.1.2;6.2 Responsible Dietary Factor;103
6.1.1.3;6.3 Mechanisms Underlying Life Extension and Related Antiaging Actions;104
6.1.1.3.1;6.3.1 Growth Retardation Hypothesis;104
6.1.1.3.2;6.3.2 Reduced Body Fat Hypothesis;105
6.1.1.3.3;6.3.3 Decreased Metabolic Rate Hypothesis;106
6.1.1.3.4;6.3.4 Oxidative Damage Attenuation Hypothesis;108
6.1.1.3.5;6.3.5 Decreased Glycemia Hypothesis;110
6.1.1.3.6;6.3.6 Insulin Hypotheses;111
6.1.1.3.6.1;6.3.6.1 Increased Insulin Sensitivity Hypothesis;111
6.1.1.3.6.2;6.3.6.2 Decreased Insulin Signaling Hypothesis;112
6.1.1.3.6.3;6.3.6.3 Reconciling the Two Hypotheses;112
6.1.1.3.7;6.3.7 The Growth Hormone/Insulin-Like Growth Factor I Hypothesis;112
6.1.1.3.8;6.3.8 The Hormesis Hypothesis;114
6.1.1.3.8.1;6.3.8.1 Hormesis: Definitions and Concepts;114
6.1.1.3.8.2;6.3.8.2 Caloric Restriction, A Low-Intensity Stressor;115
6.1.1.3.8.3;6.3.8.3 Caloric Restriction, A Hormetic Agent;115
6.1.1.3.8.4;6.3.8.4 Relevance of the Hormetic Action of Caloric Restriction to Life Extension and Aging;115
6.1.1.4;6.4 Conclusions: Synthesis of Current Knowledge;116
6.1.2;References;118
7;Sell_Ch07_O.pdf;1
7.1;Chapter 7;125
7.1.1;Growth Hormone and Aging in Mice;125
7.1.1.1;7.1 Introduction;126
7.1.1.2;7.2 Life Span;127
7.1.1.3;7.3 Mechanisms Contributing to Aging Processes;129
7.1.1.3.1;7.3.1 Growth and Body Size;129
7.1.1.3.2;7.3.2 Reproduction;130
7.1.1.3.3;7.3.3 Metabolism;130
7.1.1.3.4;7.3.4 Stress Resistance;131
7.1.1.4;7.4 Premature or Accelerated Aging;133
7.1.1.5;7.5 Conclusions;134
7.1.2;References;135
8;Sell_Ch08_O.pdf;1
8.1;Chapter 8;142
8.1.1;Exploiting Natural Variation in Life Span to Evaluate Mechanisms of Aging;142
8.1.1.1;8.1 Introduction;142
8.1.1.2;8.2 Relation Between MLS and Body Size;143
8.1.1.3;8.3 Comparative Approach;145
8.1.1.4;8.4 Animal Models;145
8.1.1.5;8.5 Insights from Comparative Studies;146
8.1.1.6;8.6 Conclusions;147
8.1.2;References;148
9;Sell_Ch09_O.pdf;1
9.1;Chapter 9;149
9.1.1;Slow Aging: Insights from an Exceptionally Long-Lived Rodent, the Naked Mole-Rat;149
9.1.1.1;9.1 Introduction;150
9.1.1.2;9.2 Biological Features of the Naked Mole-Rat;153
9.1.1.3;9.3 Age-related Changes in Mortality Rate;154
9.1.1.4;9.4 Reproductive Function and Age;155
9.1.1.5;9.5 Age-related changes in physiology;156
9.1.1.6;9.6 Age-related Changes in Biochemical and Molecular Markers;159
9.1.1.7;9.7 Conclusions;161
9.1.2;References;162
10;Sell_Ch10_O.pdf;1
10.1;Chapter 10;165
10.1.1;Life Extension in the Short-Lived Fish Nothobranchius furzeri;165
10.1.1.1;10.1 Introduction;166
10.1.1.2;10.2 Teleost Fishes as a Model for Studies of Aging;166
10.1.1.3;10.3 N. furzeri: An Extremely Short-Lived Vertebrate;167
10.1.1.4;10.4 Age-related Markers in N. furzeri;170
10.1.1.5;10.5 Life Extension by Temperature;171
10.1.1.6;10.6 Life Extension by Resveratrol;172
10.1.1.7;10.7 The Mechanism(s) of Action of Resveratrol;172
10.1.1.8;10.8 Nothobranchius as a Genetic Model for Aging Studies;174
10.1.1.9;10.9 Conclusions and Future Perspectives;175
10.1.2;References;175
11;Sell_Ch11_O.pdf;1
11.1;Chapter 11;181
11.1.1;Aging and Longevity in Animal Models and Humans;181
11.1.1.1;11.1 Human Aging and Longevity Within an Evolutionary Perspective;182
11.1.1.2;11.2 Advantages and Successes of Model Systems: The Crucial Importance of the Reductionist Approach;183
11.1.1.3;11.3 Disadvantages and Intrinsic Constraints of Model Systems;184
11.1.1.4;11.4 Studies on Human Aging and Longevity;186
11.1.1.5;11.5 Similar Results on Longevity Among Species;187
11.1.1.5.1;11.5.1 SIRT3;187
11.1.1.5.2;11.5.2 Insulin and Insulin-Like Growth Factor-I Signaling Pathway;187
11.1.1.5.3;11.5.3 TP53;188
11.1.1.5.4;11.5.4 Nuclear Factor-k?B System;190
11.1.1.6;11.6 Conflicting or Unavailable Results on Longevity in Different Species;191
11.1.1.6.1;11.6.1 p66Shc;191
11.1.1.6.2;11.6.2 PON1;191
11.1.1.6.3;11.6.3 Caloric Restriction;191
11.1.1.7;11.7 Conclusions;192
11.1.2;References;193