Sell_Ch01_O.pdf	1
	Sell_Ch01_O.pdf	1
	Chapter 1	17
	Reprogramming Cell Survival and Longevity: The Role of Tor, Sch9, Ras, and Sir2	17
	1.1 Introduction	17
	1.2 The S. cerevisiae Chronological Life Span	18
	1.3 High-Metabolism Survival in Synthetic Dextrose Complete Medium	19
	1.4 Severe Calorie Restriction: Survival in Water	21
	1.5 Yeast Replicative Life Span	21
	1.6 Evolutionarily Conserved Proaging Pathways	22
	1.7 The Genetics of Chronological Aging: Reprogramming Stress Resistance and Cell Survival	22
	1.8 Sir2 and Yeast Chronological Aging	25
	1.9 Evolutionary Conserved Proaging Pathways	26
	1.10 Conclusions	28
	References	28
	Sell_Ch02_O.pdf	1
	Chapter 2	34
	Common Aging Mechanisms: Energy Metabolism and Longevity in Caenorhabditis elegans	34
	2.1 Introduction	35
	2.2 The Insulin Signaling Pathway	35
	2.3 Caloric Restriction	38
	2.4 Mitochondrial Dynamics	39
	2.5 Conclusions	41
	References	42
	Sell_Ch03_O.pdf	1
	Chapter 3	46
	Conserved Mechanisms of Life-Span Regulation and Extension in Caenorhabditis elegans	46
	3.1 Caenorhabditis elegans as a Discovery Engine	47
	3.2 The Major Axes of Life-Span Regulation in C. elegans	47
	3.2.1 The Genetics of Aging	48
	3.2.2 Endocrine Signaling	49
	3.2.2.1 Insulin-Like Signaling	50
	3.2.2.2 Transforming Growth Factor-b-Like Signaling	52
	3.2.2.3 Tissue Specificity of Endocrine Signaling	53
	3.2.2.4 C. elegans Insulin Signaling and Human Disease	54
	3.2.3 Reproduction	54
	3.2.4 Dietary Restriction	55
	3.2.5 Mitochondria	57
	3.3 Next Generation Studies to Identify Life-Span Regulators	58
	3.3.1 RNA Interference	58
	3.3.1.1 RNAi Screens for Increased Life-Span Phenotypes	59
	3.3.1.2 Specialized RNAi Screens for Life-Span Phenotypes	60
	3.3.2 Chemical Screens	62
	References	63
	Sell_Ch04_O.pdf	1
	Chapter 4	71
	The Genetic Architecture of Longevity	71
	4.1 The Three Types of Longevity Responses	72
	4.2 The Three Phases of the Life Span	76
	4.2.1 The Developmental Span	76
	4.2.2 The Health Span	76
	4.2.3 The Senescent Span	78
	4.3 The Genetic Architecture of Longevity	82
	References	84
	Sell_Ch05_O.pdf	1
	Chapter 5	86
	Mild Stress and Life Extension in Drosophila melanogaster	86
	5.1 Introduction	86
	5.2 Hypergravity	87
	5.2.1 Hypergravity Increases Longevity of Males	87
	5.2.2 Hypergravity Can Delay Behavioral Aging	89
	5.2.3 Hypergravity Increases Resistance to Heat But Not to Other Stresses	89
	5.3 Heat	91
	5.3.1 Heat Can Slightly Increase Longevity	91
	5.3.2 Heat Does Not Clearly Delay Behavioral Aging	91
	5.3.3 Heat Increases Resistance to Some Stresses	92
	5.4 Cold	92
	5.4.1 Cold Increases Longevity	92
	5.4.2 Cold Can Delay Behavioral Aging	92
	5.4.3 Cold Increases Resistance to Some Stresses	92
	5.5 Irradiation	94
	5.5.1 Irradiation at the Egg Stage Increases Longevity	94
	5.5.2 Can Irradiation Delay Behavioral Aging?	94
	5.5.3 Irradiation Decreases Resistance to Heat and Desiccation	95
	5.6 What Are the Causes of Hormesis?	96
	5.7 Conclusions	97
	References	98
	Sell_Ch06_O.pdf	1
	Chapter 6	101
	Global Food Restriction	101
	6.1 Overview	102
	6.1.1 Life Extension	102
	6.1.2 Retardation of Physiological Deterioration	103
	6.1.3 Retardation of Age-Associated Diseases	103
	6.2 Responsible Dietary Factor	103
	6.3 Mechanisms Underlying Life Extension and Related Antiaging Actions	104
	6.3.1 Growth Retardation Hypothesis	104
	6.3.2 Reduced Body Fat Hypothesis	105
	6.3.3 Decreased Metabolic Rate Hypothesis	106
	6.3.4 Oxidative Damage Attenuation Hypothesis	108
	6.3.5 Decreased Glycemia Hypothesis	110
	6.3.6 Insulin Hypotheses	111
	6.3.6.1 Increased Insulin Sensitivity Hypothesis	111
	6.3.6.2 Decreased Insulin Signaling Hypothesis	112
	6.3.6.3 Reconciling the Two Hypotheses	112
	6.3.7 The Growth Hormone/Insulin-Like Growth Factor I Hypothesis	112
	6.3.8 The Hormesis Hypothesis	114
	6.3.8.1 Hormesis: Definitions and Concepts	114
	6.3.8.2 Caloric Restriction, A Low-Intensity Stressor	115
	6.3.8.3 Caloric Restriction, A Hormetic Agent	115
	6.3.8.4 Relevance of the Hormetic Action of Caloric Restriction to Life Extension and Aging	115
	6.4 Conclusions: Synthesis of Current Knowledge	116
	References	118
	Sell_Ch07_O.pdf	1
	Chapter 7	125
	Growth Hormone and Aging in Mice	125
	7.1 Introduction	126
	7.2 Life Span	127
	7.3 Mechanisms Contributing to Aging Processes	129
	7.3.1 Growth and Body Size	129
	7.3.2 Reproduction	130
	7.3.3 Metabolism	130
	7.3.4 Stress Resistance	131
	7.4 Premature or Accelerated Aging	133
	7.5 Conclusions	134
	References	135
	Sell_Ch08_O.pdf	1
	Chapter 8	142
	Exploiting Natural Variation in Life Span to Evaluate Mechanisms of Aging	142
	8.1 Introduction	142
	8.2 Relation Between MLS and Body Size	143
	8.3 Comparative Approach	145
	8.4 Animal Models	145
	8.5 Insights from Comparative Studies	146
	8.6 Conclusions	147
	References	148
	Sell_Ch09_O.pdf	1
	Chapter 9	149
	Slow Aging: Insights from an Exceptionally Long-Lived Rodent, the Naked Mole-Rat	149
	9.1 Introduction	150
	9.2 Biological Features of the Naked Mole-Rat	153
	9.3 Age-related Changes in Mortality Rate	154
	9.4 Reproductive Function and Age	155
	9.5 Age-related changes in physiology	156
	9.6 Age-related Changes in Biochemical and Molecular Markers	159
	9.7 Conclusions	161
	References	162
	Sell_Ch10_O.pdf	1
	Chapter 10	165
	Life Extension in the Short-Lived Fish Nothobranchius furzeri	165
	10.1 Introduction	166
	10.2 Teleost Fishes as a Model for Studies of Aging	166
	10.3 N. furzeri: An Extremely Short-Lived Vertebrate	167
	10.4 Age-related Markers in N. furzeri	170
	10.5 Life Extension by Temperature	171
	10.6 Life Extension by Resveratrol	172
	10.7 The Mechanism(s) of Action of Resveratrol	172
	10.8 Nothobranchius as a Genetic Model for Aging Studies	174
	10.9 Conclusions and Future Perspectives	175
	References	175
	Sell_Ch11_O.pdf	1
	Chapter 11	181
	Aging and Longevity in Animal Models and Humans	181
	11.1 Human Aging and Longevity Within an Evolutionary Perspective	182
	11.2 Advantages and Successes of Model Systems: The Crucial Importance of the Reductionist Approach	183
	11.3 Disadvantages and Intrinsic Constraints of Model Systems	184
	11.4 Studies on Human Aging and Longevity	186
	11.5 Similar Results on Longevity Among Species	187
	11.5.1 SIRT3	187
	11.5.2 Insulin and Insulin-Like Growth Factor-I Signaling Pathway	187
	11.5.3 TP53	188
	11.5.4 Nuclear Factor-k?B System	190
	11.6 Conflicting or Unavailable Results on Longevity in Different Species	191
	11.6.1 p66Shc	191
	11.6.2 PON1	191
	11.6.3 Caloric Restriction	191
	11.7 Conclusions	192
	References	193