The Genetics of Aging, Softcover reprint of the original 1st ed. 1978

The Genetics of Aging is divided into several sections in an attempt to provide a logical progression from the level of the genome to the realm of human genetics. The relationship between the genetic material and aging will be thoroughly explored in the initial chapters. These chapters discuss in depth the various theories that have been proposed for the mechanisms of aging at the molecular level and present data which either support or contradict these hypotheses. Subsequent chapters will deal with the genetics of aging in organisms ranging from paramecium to mammals. The largest section of this volume will be devoted to several important areas in human genetics: human genetic disorders which feature premature aging, the effect of human parental aging on the production of genetically abnor­ mal offspring, the genetics of human longevity, and a review of studies on aging human twins. Over the last few decades genetic technology has provided enormous insight into a number of disciplines. Therefore, in the last few chapters, several genetic approaches to the study of aging are discussed: somatic cell genetics, immunogenetics, and behavioral genetics. As the goal of this volume is to present a comprehensive examination of the genetics of aging, most chapters are oriented toward general review of their respective areas. It is my hope that this volume will encourage clinical, biological, and behavioral investigators to turn their attention to the genetic aspects of aging as well as to employ genetic technology to obtain further insight into aging processes.

I. Genome Level.- 1 Molecular Genetics of Aging.- 1. Introduction.- 2. Mechanisms for the Inheritance of the Patterns of Senescence and Longevity.- 2.1. Explicit Inheritance.- 2.2. Implicit Inheritance.- 3. Molecular-Genetic Mechanisms of Senescence.- 3.1. Altered Molecules.- 3.1.1. Somatic Mutations.- 3.1.2. Error Catastrophe.- 3.1.3. Compensation and Repair.- 3.2. Programmed Aging.- 4. Conclusion.- References.- 2 Cytogenetics of Aging.- 1. Introduction.- 2. Alterations in Lymphocyte Chromosome Complement with Human Aging.- 3. Population Studies.- 4. Aneuploidy, Aging, and Organic Brain Disease.- 5. Effect of Genotype on Aneuploidy.- 6. Specific vs. Nonspecific Chromosome Loss.- 7. Polyploidy.- 8. Cross-Sectional vs. Longitudinal Studies.- 9. Chromosomal Alterations with Aging in Tissues Other than Lymphocytes.- 10. Effect of Experimental Conditions on Chromosome Number.- 11. In Vivo Examination of Aneuploidy.- 12. Studies of the Stability of the Chromosome Complement with in Vitro “Aging”.- 13. Chromosomal Alteration, Malignancy, and Aging.- 14. Mechanisms for the Loss of Specific Chromosomes with Aging.- 14.1. Survival of Cells Missing Specific Chromosomes.- 14.2. Selective Loss of Specific Chromosomes.- 14.3. Effect of Aging on Selection.- 15. Future Research on the Cytogenetics of Aging.- 16. Summary.- References.- 3 Aging and DNA-Repair Capability.- 1. Introduction.- 2. DNA-Repair Processes.- 2.1. Strand-Breakage Rejoining.- 2.2. Excision Repair.- 2.3. Postreplication Repair.- 2.4. Photoreactivation.- 2.5. Assay Systems for DNA Repair.- 3. Age-Related Occurrence of Unrepaired DNA Lesions.- 3.1. DNA Strand Breakage.- 3.2. DNA Cross-Linking.- 3.3. Chromosome Aberrations.- 4. DNA-Repair Capability as a Function of Age.- 4.1. In Vitro Investigations.- 4.2. In Vivo Investigations.- 5. Tissue-Specific DNA-Repair Capability.- 6. Acceleration of the Aging Process by Exposure to DNA-Damaging Agents.- 7. Human Genetic Syndromes.- 7.1. Syndromes of DNA-Repair Deficiency.- 7.2. Syndromes of Accelerated Aging.- 7.3. Conclusions.- 8. Longevity and DNA-Repair Processes.- 9. Summary and Conclusion.- References.- 4 Somatic Mutations and Aging.- 1. Introduction.- 2. Terminology of Mutagenesis.- 2.1. Concepts and Definitions.- 2.2. Mutations in Nondividing Cells.- 3. Metabolic Stability of DNA: Contrast to Turnover of Intracellular Macromolecules.- 4. Accumulation of Somatic Mutations with Aging.- 4.1. Chromosome Aberrations.- 4.2. Distinguishing Somatic Mutations from Errors.- 4.3. Base-Substitution Mutations.- 4.4. Germinal vs. Somatic Mutations.- 5. Mutagens, Carcinogens, Cancer, and Aging.- 5.1. Age-Associated Incidence of Cancer in Man and Other Mammals.- 5.2. Mutagenicity of Chemical Carcinogens.- 6. Special Genetic Mechanisms of Aging.- 7. Summary.- References.- II. Organism Level.- 5 Genetics of Aging in Lower Organisms.- 1. Introduction.- 2. Inheritance of Life Span.- 2.1. Effect of Chromosome Number on Longevity.- 2.2. Effect of Genotype on Longevity.- 2.3. Cytoplasmic Inheritance of Aging in Fungi.- 2.4. Effect of Parental Age on Longevity.- 3. Induction of Aging in Immortal Organisms.- 3.1. “Spanning” of Amoeba.- 3.2. Mutants of Neurospora.- 3.3. Autogamy-Deprived Paramecia.- 4. Summary and Conclusions.- References.- 6 Evolution of Longevity and Survival Characteristics in Mammals.- 1. Introduction.- 2. Evolutionary Gerontology: What Evolved, Aging or Longevity?.- 2.1. Allometry of Vertebrate Life Span.- 2.2. “Senescence Gene” Hypothesis of the Evolution of Aging.- 2.3. Evolution of Longevity by Means of Longevity-Assurance Genes.- 3. Evolution of Longevity in Man and the Other Mammals.- 4. Life Tables for Natural Populations.- 5. Evolutionary Change of the Parameters of the Gompertzian Survival Characteristic.- 6. Conclusion.- References.- III. Human Genetics.- 7 Human Genetic Disorders that Feature Premature Onset and Accelerated Progression of Biological Aging.- 1. Introduction.- 2. Specific Criteria of Aging.- 2.1. Physiological Markers.- 3. Premature Aging.- 3.1. General Criteria.- 3.2. A Specific Scoring System for Premature Aging.- 4. Description of Selected Disorders That Feature Premature Aging.- 4.1. Classic Progeroid Syndromes.- 4.2. Numerical Chromosome Anomalies.- 4.3. Miscellaneous Inherited Syndromes.- 5. Comparison of Premature Aging Syndromes with Normal Biological Aging.- 6. Tissue Culture Approaches to Premature Aging.- 6.1. Studies on Cell Growth.- 6.2. Defective Molecules in Prematurely Aging Cells.- 7. Significance of Biochemical Defects in Prematurely Aging Fibroblasts.- 7.1. Defects in Protein Turnover.- 7.2. Defects in RNA Turnover.- 7.3. Defects in DNA Repair.- 7.4. Defects in DNA Replication.- 8. Conclusions and Future Directions.- References.- 8 Parental-Age Effects: Increased Frequencies of Genetically Abnormal Offspring.- 1. Introduction.- 2. Maternal- vs. Paternal-Age Effects.- 3. Maternal-Age-Related Disorders.- 4. Paternal-Age-Related Disorders.- 5. Proposed Etiological Agents.- 5.1. Radiation.- 5.2. Chemicals.- 5.3. Autoimmunity.- 5.4. Infectious Agents.- 5.5. Genetic Predisposition.- 5.6. Preovulatory Overripeness.- 5.7. Postovulatory Aging.- 6. Mechanisms of Nondisjunction.- 6.1. Nucleolar Organization.- 6.2. Univalent Formation.- 6.3. Premature Centromere Division.- 7. Approaches to Studying Parental-Age Effects.- 8. Prevention by Genetic Counseling and Prenatal Diagnosis.- 9. Summary.- References.- 9 Genetics of Longevity in Man.- 1. Introduction.- 2. Evolutionary Implications.- 3. Genetics and Length of Life.- 3.1. Aging May Be Ineluctable.- 3.2. Aging May Be a Programmed Self-Destruction.- 3.3. Aging May Be an Exogenous Process.- 4. Analysis of Empirical Data.- 5. Models of Aging.- 5.1. External Models.- 5.2. Internal Models.- 5.3. Composite Models.- 5.4. Constructive Models.- 6. Studies of the Inheritance of Longevity.- 6.1. Previous Studies.- 6.2. The Baltimore Longevity Study.- 6.3. Our Extension of the Baltimore Study.- 7. Summary and Conclusion.- References.- 10 A Longitudinal Study of Aging Human Twins.- 1. Introduction: History, Methodology, and Purpose.- 2. Genetic Factors and Survival.- 3. Genetic Factors and Mental Functioning.- 3.1. Test-Battery Description and Initial Assessment.- 3.2. Longitudinal Changes in Psychological Test Performance.- 3.3. Psychological Testing and Prediction of Survival.- 3.4. Test Performance, Ability, and Education as Factors in Aging.- 4. Chromosome Change and Survival.- 5. Chromosome Change and Mental Functioning.- 6. Sex Differences and Survival.- 7. Sex Differences and Mental Functioning.- 8. Summary and Conclusions.- References.- IV. Genetic Approaches to Aging Research.- 11 Somatic Cell Genetics in the Analysis of in Vitro Senescence.- 1. Introduction.- 2. Biology of Cultured Mammalian Cells.- 2.1. Historical Background.- 2.2. The Phenomenon of in Vitro Senescence.- 2.3. Relevance of in Vitro Senescence to in Vivo Senescence.- 3. Phenotype of the Senescent Culture.- 3.1. Alterations of Proliferative Behavior with Senescence.- 3.2. Cytogenetic Alterations.- 3.3. Morphology.- 3.4. Implication for Genetic Studies.- 4. Somatic Cell Genetic Studies of in Vitro Cellular Senescence.- 4.1. Theories of the Mechanism of in Vitro Senescence.- 4.2. Scope of Somatic Cell Genetics.- 4.3. Heterokaryon Studies.- 4.4. Enucleation—Fusion Studies.- 4.5. Synkaryon Studies.- 5. Discussion.- References.- 12 Immunogenetics of Aging.- 1. Introduction.- 2. Histocompatibility Systems and Immune Responses.- 3. Immune Functional Changes with Age.- 3.1. T-Dependent Immune Functions.- 3.2. T-Independent Immune Functions.- 3.3. Autoimmunity.- 4. Genetic Influences of Immune Function in Aging.- 4.1. Influence of Sex.- 4.2. Influence of Strain or Race.- 4.3. Studies in Congenic Mice.- 4.4. The Major Histocompatibility (HLA System) in Humans in Relation to Aging.- 5. Immunogenetic Diseases and Aging.- 6. Summary.- References.- 13 Behavior Genetics and Aging.- 1. Introduction.- 2. Life Span.- 2.1. Inbred Mice.- 2.2. Hybrid Mice.- 2.3. Mutant Mice.- 2.4. Body-Weight Increment and Longevity.- 3. Behavior.- 3.1. Exploration and Open-Field Activity.- 3.2. Wheel Activity.- 3.3. Responsiveness to Light Onset.- 3.4. Sucrose Discrimination and Fluid Intake.- 3.5. Alcohol Preference.- 4. Summary.- References.