The molecular genetics of aging: 8 tables
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
Berlin [u.a.]
Springer
2000
|
| Schriftenreihe: | Results and problems in cell differentiation
29 |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XV, 240 S. Ill., graph. Darst. |
| ISBN: | 354066663X |
Internformat
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Datensatz im Suchindex
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|---|---|
| adam_text | Contents
Centenarians and the Genetics of Longevity
Thomas Perls, Dellara F. Terry, Margery Silver, Maureen Shea,
Jennifer Bowen, Erin Joyce, Stephen B. Ridge, Ruth Fretts, Mark Daly,
Stephanie Brewster, Annibale Puca, and Louis Kunkel
1 Introduction 1
2 Are Centenarians a New Phenomenon? 2
3 Centenarians Are the Fastest Growing Age Group 3
4 Are Centenarians Different? 4
5 The Centenarian Phenotype: Compressing Morbidity
Towards the End of Life 6
6 Evidence from Centenarians Supporting a Strong
Genetic Influence upon Longevity 7
7 Siblings of Centenarians Live Longer 7
8 Parents of Centenarians also Achieve Unusually Old Age .... 8
9 Four Families with Clustering for Extreme Longevity 8
9.1 Mathematical Analysis 10
10 Middle Aged Mothers Live Longer: An Evolutionary Link
Between Reproductive Success and Longevity Enabling Genes . 11
10.1 What Determines When a Woman Will Go Through
Menopause? 12
10.2 Menopause: An Adaptive Response 13
10.3 Why Menopause Does Not Occur in Other Mammals? 13
10.4 Nonhuman Data Supporting the Association Between Delayed
Reproductive Senescence and Increased Longevity 14
10.5 Alternative Explanations for Why Menopause Occurs 14
10.6 Why Is the Human Life Span 122 Years and What Is the
Evolutionary Advantage for Living to Such an Age? 15
10.7 What If We Removed the Selective Force
for Maximizing Life Span? 16
10.8 The Association Between Longevity Enabling Genes
and Genes Which Regulate Reproductive Health 16
11 In Our Near Future 16
References 17
X Contents
Coordination of Metabolic Activity
and Stress Resistance in Yeast Longevity
S. Michal Jazwinski
1 Introduction 21
2 Phenomenology of Yeast Aging 23
3 Genetics of Longevity 25
4 Physiological and Molecular Mechanisms of Aging 27
4.1 Genetic Instability and Gene Dysregulation 27
4.2 Metabolic Control 29
4.3 Stress Resistance 32
4.4 Coordination of Metabolic Activity and Resistance to Stress . . 34
4.5 Comparisons with Other Organisms 36
5 Primacy of Metabolic Control 38
References 39
Current Issues Concerning the Role
of Oxidative Stress in Aging: A Perspective
Rajindar S. Sohal, Robin J. Mockett, and William C. Orr
1 Introduction 45
2 The Concept of Life Span: A Cautionary Note 47
3 Metabolic Rate, Stress Resistance and Antioxidative Defenses . 49
4 Current Evidential Status of the Oxidative Stress Hypothesis
of Aging 50
5 Longevity Studies in Transgenic Drosophila 53
6 Hazards of Life Span Analysis in Drosophila 55
6.1 Compensation 55
6.2 Genetic Effects 57
6.3 Inducible Expression Systems 59
7 Conclusions 61
References 62
Regulation of Gene Expression During Aging
Stephen L. Helfand and Blanka Rogina
1 Importance of Examining Gene Expression During Aging ... 67
2 Drosophila as a Model System for Studying Gene Expression
During Aging 67
3 Enhancer Trap and Reporter Gene Techniques Can Be Used
to Study Gene Expression During Aging 68
4 The Level of Expression of Many Genes Is Dynamically
Changing During Adult Life in Drosophila melanogaster .... 69
Contents XI
5 Gene Expression Is Carefully Regulated During Adult Life
in Drosophila melanogaster 70
6 Some Genes Are Regulated by Mechanisms That Are Linked
to Life Span and May Serve as Biomarkers of Aging 70
7 The Expression of Some Genes Is Not Changed by
Environmental or Genetic Manipulations
That Alter Life Span 73
8 Use of Temporal Patterns of Gene Expression as Biomarkers
of Aging 74
9 The drop dead Mutation May Be Used to Accelerate Screens
for Long Lived Mutations 75
10 Studies on Gene Expression Suggest That Not All Things
Fall Apart During Aging 77
11 Conclusions 77
References 79
Crossroads of Aging in the Nematode Caenorhabditis elegans
Siegfried Hekimi
1 Introduction 81
1.1 Life Span Versus Aging 81
1.2 The Worm 81
1.3 Three Paths of Longevity 83
2 Dormancy 83
2.1 The Dauer Larva 83
2.2 The Genetics of Dauer Formation 85
2.3 The Molecular Identities of the Dauer Genes 87
3 The Rate of Living 88
3.1 The Identification of elk Genes 88
3.2 The clk 1 Phenotype 90
3.3 Four elk Genes 91
3.4 The Molecular Identity of clk 1 92
3.5 clk 1 Mutant Mitochondria 94
3.6 Overexpression of CLK 1 Activity 96
3.7 Acceleration of the Rate of Aging 97
3.8 clk 1, Mitochondria and the Nucleus 98
4 Caloric Restriction 99
4.1 Hungry Rats 99
4.2 Hungry Worms 100
5 How Many Different Mechanisms? 102
5.1 An Answer from Genetic Interactions 102
5.2 Rate of Living and Dormancy 103
5.3 Dormancy and Caloric Restriction 106
5.4 Rate of Living and Caloric Restriction 106
XII Contents
5.5 Additivity of elk Genes 106
5.6 Common Grounds: Metabolic Rates and the Germline 107
6 A Unifying Hypothesis 108
References 109
Contributions of Cell Death to Aging in C. elegans
Laura A. Herndon and Monica Driscoll
1 Introduction 113
2 C. elegans as Model for Analysis of Molecular Mechanisms
of Aging 113
2.1 C. elegans as a Model System 113
2.2 Characterization of Aging Nematodes 115
2.3 Genetics of Life Span in C. elegans 116
3 Cell Death 118
3.1 Programmed Cell Death 119
3.1.1 Programmed Cell Death During Development in C. elegans . . 119
3.1.2 Relation of Programmed Cell Death (Apoptosis) to Aging
in C. elegans 120
3.2 Degenerative Cell Death 121
3.2.1 Necrotic Like Cell Death in C. elegans 121
3.2.2 Neuropathology of mec 4(d) Induced Degeneration 122
3.2.3 A Link Between Necrotic Like Cell Death and Aging? 123
4 Roles of Cell Death in C. elegans Aging, Future Directions . . . 124
References 125
Stress Response and Aging in Caenorhabditis elegans
Gordon J. Lithgow
1 Introduction 131
2 C. elegans Life History Life in a Stressful Environment .... 131
3 Longevity (Age) Mutations 133
4 Aging and Stress Response 135
4.1 Is Aging a Stress? 135
4.2 Oxidative Stress and Worm Aging 136
4.3 Thermotolerance and the Age Mutants 139
4.4 UV Resistance and Aging 142
5 Stress and Life Span Determination 142
References 144
Contents XIII
Oxidative Stress and Aging in Caenorhabditis elegans
Naoaki Ishii and Philip S. Hartman
1 Introduction 149
2 Genetics and Environment Causes of Aging 150
3 Isolation of Mutants 151
4 Fecundity 152
5 Life Span 153
5.1 mev 1 153
5.2 rad 8 153
6 Aging Markers 154
6.1 Fluorescent Materials 154
6.2 Protein Carbonyls 155
7 Superoxide Dismutase (SOD) Activity 156
8 Molecular Cloning of mev 1 156
9 Enzyme Activity of Cytochrome b560 157
10 Mutagenesis 157
11 Apoptosis in mev 1 and rad 8 Mutants 158
12 Mechanism of Cell Damage by the mev 1 Mitochondrial
Abnormality 159
13 Other C. elegans Life Span Mutants Show Abnormal
Responses to Oxidative Stress 160
14 Closing Comments 161
References 162
Mutation Accumulation In Vivo and the Importance
of Genome Stability in Aging and Cancer
Martijn E. T. Dolle, Heidi Giese, Harry van Steeg, and Jan Vijg
1 Introduction 165
2 In Vivo Model Systems for Measuring Mutations 167
3 The lacZ Plasmid Mouse Model for Mutation Detection 168
4 Monitoring Mutation Accumulation in Mice with Defects
in Genome Stability Pathways 170
4.1 The TP53 Gene 171
4.2 The XPA Nucleotide Excision Repair Gene 173
5 Summary and General Discussion 177
References 178
XIV Contents
Delayed Aging in Ames Dwarf Mice.
Relationships to Endocrine Function and Body Size
Andrzej Bartke
1 Introduction 181
2 Ames Dwarf Mice 182
3 Snell Dwarf Mice 185
4 Development and Longevity of Dwarf Mice 187
5 Longevity of Snell Dwarf Mice and the Issues of Husbandry . . 189
6 Possible Mechanisms of Delayed Aging in Dwarf Mice 190
6.1 Reduced Blood Glucose and Increased Sensitivity to Insulin . . 190
6.2 Hypothyroidism 191
6.3 Reduced Body Temperature and Metabolic Rate 191
6.4 Improved Capacity to Remove Reactive Oxygen Species 192
6.5 Hypogonadism 192
6.6 Deficiency of GH and IGF I 193
6.7 GH IGF I Axis, Body Size, and Aging 194
7 General Conclusions and Future Directions 196
References 197
Stem Cells and Genetics in the Study of Development,
Aging, and Longevity
Gary Van Zant
1 Introduction 203
1.1 Definitions 203
1.2 Cancer as a Disease of Both Development and Aging 204
1.3 Stem Cells Are Life Sustaining Vestiges
of Organismal Development 205
1.4 Interrelatedness of Development and Aging Chapter Outline 206
2 Development as a Reversible Restriction
of Developmental Potential 206
2.1 What Is the Mechanism? 206
2.2 Developmental Choices Are Not Necessarily Immutable 208
3 Stem Cell Populations Drive Developmental Systems 209
3.1 Models of Stem Cell Differentiation 209
3.1.1 Clonal Succession 209
3.1.2 Flexibility in Types of Daughter Cells Produced
by Stem Cell Division 209
3.1.3 Stem Cell Populations Reflect Physiological Need While
Developmental Choices at the Individual Stem Cell Level
May Be Stochastic 210
3.2 Why Are Stem Cells Difficult to Study? 210
3.3 Renewal of Stem Cells as Revealed by Transplantation 211
Contents XV
3.4 Stem Cell Kinetics in Steady State Animals May Be Different . 213
3.5 Steady State Stem Cells Enter and Leave Cell Cycle Regularly . 214
3.6 Are Large Animals Fundamentally Different? 214
3.7 What Role for Apoptosis in a Continuously Renewing
Stem Cell System? 215
4 Stem Cell Populations as Critical Targets of Damage
During Aging 216
4.1 Cancer and Congenital Diseases 216
4.2 Hematologic Malignancies 217
4.3 All Reactive Oxygen Species Are Not Bad 217
5 Hematopoietic Stem Cells as a Model Population for Studies
of Aging 218
5.1 Availability and Ease of Study 218
5.2 Contradictory Data 218
5.3 Stem Cell Populations Age 219
5.4 Genetic Influences 220
6 Telomeres 221
6.1 Relationship to Replicative Senescence 221
6.2 Telomeres and Stem Cells 222
6.2.1 Telomere Changes After Stem Cell Transplantation 222
6.3 Telomeres and Aging 223
6.4 Telomeres and Cancer 223
7 A Link Between Stem Cell Replication and Organismal
Life Span in the Mouse 224
7.1 Study of Embryo Aggregated Chimeric Mice 224
7.2 Reversibility of Stem Cell Activation and Quiescence 225
7.3 Genetic Studies 226
7.3.1 In Vitro Assay for Stem Cells 226
7.3.2 Average Life Span Correlates with Cell Cycle Kinetics 227
7.3.3 Mapping Studies in Recombinant Inbred Mouse Strains 228
7.3.4 Quantitative Trait Loci Affecting Life Span
and Cell Cycle Kinetics Map to the Same Genomic Locations . 228
7.3.5 Mapping of a Locus Determining Variation in Mouse Life Span 229
8 Conclusions and Final Thoughts 229
References 230
Subject Index 237
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| spelling | The molecular genetics of aging 8 tables Siegfried Hekimi (ed.) Berlin [u.a.] Springer 2000 XV, 240 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Results and problems in cell differentiation 29 Altern - Molekulargenetik - Aufsatzsammlung Langlebigkeit - Molekulargenetik - Aufsatzsammlung Molekulargenetik (DE-588)4039987-4 gnd rswk-swf Langlebigkeit (DE-588)4166707-4 gnd rswk-swf Altern (DE-588)4068596-2 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Altern (DE-588)4068596-2 s Molekulargenetik (DE-588)4039987-4 s DE-604 Langlebigkeit (DE-588)4166707-4 s Hekimi, Siegfried 1956- Sonstige (DE-588)121449955 oth Results and problems in cell differentiation 29 (DE-604)BV000022913 29 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=008823251&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | The molecular genetics of aging 8 tables Results and problems in cell differentiation Altern - Molekulargenetik - Aufsatzsammlung Langlebigkeit - Molekulargenetik - Aufsatzsammlung Molekulargenetik (DE-588)4039987-4 gnd Langlebigkeit (DE-588)4166707-4 gnd Altern (DE-588)4068596-2 gnd |
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| title | The molecular genetics of aging 8 tables |
| title_auth | The molecular genetics of aging 8 tables |
| title_exact_search | The molecular genetics of aging 8 tables |
| title_full | The molecular genetics of aging 8 tables Siegfried Hekimi (ed.) |
| title_fullStr | The molecular genetics of aging 8 tables Siegfried Hekimi (ed.) |
| title_full_unstemmed | The molecular genetics of aging 8 tables Siegfried Hekimi (ed.) |
| title_short | The molecular genetics of aging |
| title_sort | the molecular genetics of aging 8 tables |
| title_sub | 8 tables |
| topic | Altern - Molekulargenetik - Aufsatzsammlung Langlebigkeit - Molekulargenetik - Aufsatzsammlung Molekulargenetik (DE-588)4039987-4 gnd Langlebigkeit (DE-588)4166707-4 gnd Altern (DE-588)4068596-2 gnd |
| topic_facet | Altern - Molekulargenetik - Aufsatzsammlung Langlebigkeit - Molekulargenetik - Aufsatzsammlung Molekulargenetik Langlebigkeit Altern Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=008823251&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV000022913 |
| work_keys_str_mv | AT hekimisiegfried themoleculargeneticsofaging8tables |