| Chapter 1 Basic Concepts In The Biology Of Aging |
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1 | (36) |
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Biogerontology: Study Of Biological Aging |
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2 | (5) |
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Biologists began studying aging when human life spans increased |
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2 | (1) |
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Biogerontology became independent field of research during 1940s |
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3 | (1) |
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Current aging research considers health of the total person |
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4 | (1) |
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Biological aging in nonhuman species shares many traits observed in human aging |
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4 | (1) |
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Study of aging is complex process |
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Cause and mechanisms of aging are two separate but linked processes |
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6 | (1) |
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Definitions Of Biological Aging |
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7 | (5) |
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First definitions of biological aging were based on mortality |
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7 | (1) |
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Functional-based definitions help describe biological aging over specific time periods |
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8 | (1) |
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Definition of aging for Biology of Aging |
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9 | (1) |
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Development, maturity, and senescence are event-related stages used to describe aging |
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9 | (2) |
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Biological aging is distinct from diseases of old age |
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11 | (1) |
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How Biogerontologists Study Aging: Use Of Laboratory Organisms In Human Aging Research |
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12 | (7) |
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Isolated cell systems can be studied to describe basic biochemistry of aging and longevity |
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14 | (1) |
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Fungi are good models for studying environmental factors that affect aging and longevity |
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15 | (1) |
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Primitive invertebrates may provide clues to extended cellular life, cell signaling, and whole-body aging |
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16 | (1) |
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Insects can be used to investigate how whole-body and intracellular signaling affect life history |
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17 | (1) |
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Mice and rats are common research subjects in investigation of nutritional, genetic, and physiological questions |
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17 | (1) |
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Nonhuman primates display many of same time-dependent changes as humans |
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17 | (2) |
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Human progerias can be used to model normal human aging |
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19 | (1) |
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How Biogerontologists Study Aging: Comparative Biogerontology |
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19 | (5) |
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Species' body size related to maximum life span |
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20 | (1) |
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Reduced vulnerability to extrinsic dangers explains extended longevity |
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21 | (1) |
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Highly organized social structure also extends longevity in wild |
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22 | (1) |
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A few aquatic animals have extreme longevity |
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23 | (1) |
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Planaria and hydra have negligible senescence and extreme longevity associated with high capacity for tissue regeneration |
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24 | (1) |
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How Biogerontologists Study Aging: Systems Biology |
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24 | (9) |
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Systems biology will help transform biology into a predictive science |
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25 | (1) |
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Reductive method of science has characterized biological research |
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25 | (1) |
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Systems biology and reductionism work together to increase knowledge and improve predictions |
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26 | (3) |
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Reductionism can predict emergent properties in simple biological systems; complex systems require quantitative methods |
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29 | (1) |
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Modern systems biology and "omics" sciences began with sequencing of human genome |
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29 | (1) |
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Biological networks provide method of evaluating interactions within system |
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30 | (3) |
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33 | (1) |
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34 | (1) |
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35 | (1) |
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36 | (1) |
| Chapter 2 Measuring Biological Aging |
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37 | (30) |
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Measuring Biological Aging In The Individual |
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37 | (14) |
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Differences in age-related phenotype affect measurement of aging in individuals |
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39 | (2) |
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Lifestyle choices significantly affect phenotype |
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41 | (2) |
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Cross-sectional studies compare changes in different age groups at single point in time |
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43 | (1) |
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Longitudinal studies observe changes in a single individual over time |
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44 | (4) |
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A precise and accurate biomarker of aging will be developed through the Precision Medicine Initiative |
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48 | (3) |
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Measuring Biological Aging In Population |
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51 | (12) |
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Mortality rates estimate number of deaths in populations |
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52 | (1) |
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Life tables contain information on mortality, life expectancy, and probability of dying |
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52 | (2) |
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Age-specific mortality rate rises exponentially |
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54 | (1) |
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Age-independent mortality can affect mortality rate |
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55 | (2) |
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Mortality-rate doubling time corrects for differences in initial mortality rates |
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57 | (2) |
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Survival curves approximate mortality rate |
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59 | (2) |
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Deceleration of mortality rate at end of life suggests possibility of longevity genes |
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61 | (1) |
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Era of precision medicine will change way we measure rate of aging in population |
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62 | (1) |
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63 | (1) |
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63 | (1) |
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64 | (1) |
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65 | (2) |
| Chapter 3 Evolutionary Theories Of Longevity And Aging |
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67 | (26) |
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Foundations Of Evolutionary Theories Of Longevity And Aging |
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67 | (10) |
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Weismann established separation between soma and germ cells |
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68 | (1) |
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Weismann proposed that aging is a nonadaptive trait |
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69 | (3) |
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Population biologists developed logistic equations to calculate population growth |
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72 | (1) |
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Population age structure describes Darwinian fitness in complex eukaryotes |
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73 | (1) |
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Reproduction rate describes age-specific fitness in breeding populations |
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74 | (1) |
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Fisher described the relationship between reproductive potential and Darwinian fitness in populations |
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75 | (2) |
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77 | (5) |
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Extrinsic rate of aging leads to decline in force of natural selection |
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77 | (1) |
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Medawar theorized that aging arose as result of genetic drift |
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78 | (2) |
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Medawar proposed that aging and longevity arise separately in postreproductive populations |
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80 | (1) |
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Hamilton's force of natural selection on mortality refined Medawar's theory |
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80 | (2) |
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Testing Evolutionary Models Of Longevity |
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82 | (3) |
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Late-reproducing organisms have a lower rate of intrinsic mortality |
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82 | (1) |
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Genetic drift links life span to reproduction |
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82 | (2) |
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Results from testing the evolutionary theory of longevity changed research in biogerontology |
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84 | (1) |
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85 | (2) |
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Antagonistic pleiotropy is a special case of general pleiotropy |
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85 | (1) |
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Disposable soma theory is based on allocation of finite resources |
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86 | (1) |
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87 | (1) |
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88 | (1) |
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89 | (1) |
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90 | (3) |
| Chapter 4 Cellular Aging |
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93 | (40) |
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Cell Cycle And Cell Division |
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93 | (3) |
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Cell cycle consists of four phases plus one |
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93 | (1) |
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DNA replication occurs during S phase |
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94 | (1) |
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Cell division occurs during the M phase |
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94 | (2) |
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Regulation Of The Cell Cycle |
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96 | (6) |
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S-cyclins and cyclin-dependent kinases initiate DNA replication |
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97 | (1) |
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The p53 pathway can prevent DNA replication at G1-to-S phase transition |
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98 | (1) |
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Many proteins are involved in replication of DNA |
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98 | (1) |
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Cohesins and condensins help control chromosome segregation |
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98 | (1) |
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Metaphase-to-anaphase transition marks final checkpoint in cell cycle |
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99 | (1) |
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Fully functional cells can exit cycle at G0 phase |
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100 | (1) |
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Program cell death-apoptosis-is normal part of development and tissue maintenance |
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101 | (1) |
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102 | (7) |
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A mistake delayed discovery of cell senescence for 50 years |
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102 | (1) |
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Hayflick's and Moorhead's research findings created field of cytogerontology |
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103 | (1) |
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Cells in culture have three phases of growth |
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104 | (2) |
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Senescent cells have several common features |
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106 | (2) |
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Cell senescence may protect cell against cancer |
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108 | (1) |
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Mechanisms inducing cell senescence are not known |
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108 | (1) |
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Cause Of Cellular Aging: Accumulation Of Damaged Biomolecules |
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109 | (4) |
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Biomolecules are subject to laws of thermodynamics |
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109 | (1) |
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Life requires constant maintenance of order and free energy |
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110 | (1) |
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Mechanism underlying aging is loss of molecular fidelity |
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111 | (1) |
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Aging reflects intracellular accumulation of damaged biomolecules |
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112 | (1) |
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Metabolic Basis Of Cellular Aging |
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113 | (12) |
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Multicellular organisms arose when oxygen levels in atmosphere increased |
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113 | (1) |
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Oxidative metabolism creates reactive oxygen species |
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114 | (2) |
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Mitochondrial ATP synthesis produces majority of superoxide ions |
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116 | (3) |
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Enzymes catalyze reduction of superoxide radical to water |
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119 | (1) |
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Cytosolic reduction also generates free radicals |
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119 | (1) |
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Oxygen-centered free radicals lead to accumulation of damaged biomolecules |
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119 | (2) |
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Cell membranes are susceptible to damage by reactive oxygen species |
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121 | (2) |
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Antagonistic pleiotropy explains aging mechanism leading to damage caused by reactive oxygen species |
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123 | (2) |
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Telomeres And Cell Senescence |
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125 | (4) |
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Telomeres prevent lagging strands from removing vital DNA sequences |
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126 | (1) |
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Shortening of telomere may cause somatic cell senescence |
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127 | (2) |
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Short telomeres are associated with time-dependent functional loss and pathology |
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129 | (1) |
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129 | (1) |
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130 | (1) |
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131 | (1) |
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132 | (1) |
| Chapter 5 Genetics Of Longevity |
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133 | (52) |
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Overview Of Gene Expression In Eukaryotes |
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133 | (8) |
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Transcription of DNA produces complementary RNA |
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134 | (2) |
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Eukaryotic cells modify RNA after transcription |
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136 | (1) |
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Translation is RNA-directed synthesis of a protein |
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137 | (2) |
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Proteins can be modified or degraded after translation |
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139 | (2) |
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Regulation Of Gene Expression |
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141 | (6) |
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Gene expression can be controlled by changing nucleosome structure: The epigenome |
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141 | (3) |
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Gene expression is controlled by binding of proteins to DNA |
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144 | (1) |
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Posttranscriptional mechanisms can also control gene expression |
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145 | (2) |
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Analyzing Gene Expression In Biogerontology |
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147 | (12) |
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Genetic analysis in biogerontology begins with the screening of mutants |
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148 | (1) |
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Identification of gene function requires DNA cloning |
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149 | (1) |
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Function of gene can be partially determined from its sequence |
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150 | (5) |
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In situ hybridization can reveal gene's function |
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155 | (1) |
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Genetically altering organisms helps evaluate gene's impact on human longevity |
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155 | (3) |
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DNA microarrays used to evaluate gene expression patterns at different ages |
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158 | (1) |
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Genetic Regulation Of Longevity In Saccharomyces Cerevisiae |
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159 | (5) |
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Saccharomyces cerevisiae reproduces both asexually and sexually |
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159 | (1) |
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Environmental conditions influence reproduction and life span |
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160 | (1) |
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Structural alteration in DNA affects life span |
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161 | (1) |
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SIR2 pathway linked to longevity |
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162 | (1) |
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Loss-of-function mutations in nutrient-responsive pathways may extend life span: Target of rapamycin |
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163 | (1) |
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Genetic Regulation Of Longevity In Caenorhabditis Elegans |
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164 | (6) |
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Regulation of dauer formation extends life span |
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165 | (1) |
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Genetic pathways regulate dauer formation |
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166 | (2) |
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Weak mutations in daf-2 extend life span |
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168 | (1) |
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The daf-2 gene links longevity to neuroendocrine control |
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169 | (1) |
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Mitochondrial proteins may be link between extended life span and metabolism |
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169 | (1) |
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Genetic Regulation Of Longevity In Drosophila Melanogaster |
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170 | (4) |
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Drosophila has a long history in genetic research |
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171 | (1) |
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Genes that extend longevity are associated with increased stress resistance |
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171 | (2) |
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Genes controlling Drosophila's growth also extend life span |
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173 | (1) |
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Genetic Regulation Of Longevity In Mus Musculus |
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174 | (7) |
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Many Mus musculus genes reported to affect longevity |
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175 | (2) |
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Decreased insulin signaling links retarded growth to longevity |
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177 | (1) |
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Diminished growth hormone signaling links insulin-like signaling pathways to increased longevity |
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178 | (2) |
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Genetic regulation of longevity demonstrated in mice has implications for human aging |
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180 | (1) |
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181 | (1) |
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181 | (2) |
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183 | (1) |
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184 | (1) |
| Chapter 6 Plant Senescence |
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185 | (24) |
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186 | (4) |
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Plant cells have cell wall, central vacuole, and plastids |
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186 | (1) |
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Photosynthesis takes place in chloroplast |
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187 | (2) |
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Plant hormones regulate growth and development |
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189 | (1) |
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Biology Of Plant Senescence |
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190 | (11) |
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Mitotic senescence occurs in cells of apical meristem |
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191 | (1) |
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Postmitotic plant senescence involves programmed and stochastic processes |
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192 | (2) |
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Leaves of Arabidopsis thaliana are model for plant senescence |
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194 | (1) |
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Leaf senescence is three-step process |
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195 | (1) |
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Monosaccharides have important role in leaf senescence |
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196 | (2) |
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Breakdown of the chloroplast provides nitrogen and minerals for other plant organs |
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198 | (1) |
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Catabolic by-products may stimulate expression of genes involved in organelle dismantling |
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199 | (1) |
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Plant membranes degrade during leaf senescence |
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200 | (1) |
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Initiating Plant Senescence |
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201 | (4) |
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Light intensity affects initiation of plant senescence |
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201 | (2) |
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Cytokinins delay senescence |
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203 | (1) |
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Other plant hormones induce senescence |
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204 | (1) |
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205 | (1) |
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206 | (1) |
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207 | (1) |
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207 | (2) |
| Chapter 7 Human Longevity And Life Span |
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209 | (24) |
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Origins Of Human Longevity |
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210 | (11) |
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Human mortality rates are facultative |
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210 | (1) |
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Genetic factors cause significant plasticity in human mortality rates |
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211 | (1) |
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Mortality rates differ in long-lived humans |
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212 | (1) |
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Genome-wide association studies identify genes associated with complex trait of human longevity |
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212 | (5) |
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Human intelligence altered mortality rates |
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217 | (1) |
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Human intelligence produced a unique longevity trajectory |
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218 | (1) |
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Heredity has only a minor influence on human life span |
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219 | (2) |
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Rise Of Extended Human Life Span In Twentieth Century |
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221 | (8) |
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For most of human history, average human life span was less than 45 years |
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221 | (2) |
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Control of infectious diseases increased mean life span |
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223 | (1) |
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Decreases in infant mortality increased life expectancy |
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224 | (2) |
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Improved medical treatments account for continuing increase in life expectancy |
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226 | (2) |
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Women have longer mean life expectancy than men |
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228 | (1) |
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229 | (2) |
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231 | (1) |
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231 | (1) |
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232 | (1) |
| Chapter 8 Common Functional Loss Associated With Aging |
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233 | (56) |
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Changes In Body Composition And Energy Metabolism |
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234 | (6) |
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Energy balance is difference between intake and expenditure |
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234 | (2) |
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Accumulation of fat occurs throughout maturity |
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236 | (4) |
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Excessive loss of body weight near end of life span associated with mortality rate |
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240 | (1) |
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Changes In Skeletal Muscle |
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240 | (14) |
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Muscle contraction is result of molecular interactions between actin and myosin proteins within sarcomere |
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241 | (3) |
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Process of skeletal muscle contraction begins as neurologic signal |
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244 | (1) |
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Skeletal muscle contraction speed and force are determined by muscle fiber type |
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245 | (2) |
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Skeletal muscle damage repair and renewal performed by satellite cells |
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247 | (2) |
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Lack of physical activity and intrinsic aging influence time-dependent loss of muscle mass |
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249 | (1) |
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Time-dependent loss in skeletal muscle strength and power correlate with aging muscle atrophy |
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249 | (1) |
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Intrinsic underlying mechanisms causing aging muscle atrophy are multifactorial and remain unresolved |
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250 | (1) |
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Denervation of motor neurons and structural fragmentation in neuromuscular junction are hallmarks of aging muscle |
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251 | (1) |
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Satellite cell function decreases over time |
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251 | (2) |
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Sarcopenia is pathological condition associated with excessive aging muscle atrophy and strength |
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253 | (1) |
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254 | (4) |
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Skin consists of three layers |
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254 | (1) |
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Wrinkles are caused by loss of skin elasticity and subcutaneous fat |
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255 | (1) |
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Ultraviolet light causes significant damage to skin over time |
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255 | (3) |
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Changes In Senses: Hearing, Vision, Taste, And Smell |
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258 | (8) |
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Sense of hearing is based on physics of sound |
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258 | (1) |
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Transmission of sound through human ear occurs in three steps |
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259 | (1) |
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Loss of stereocilia contributes to time-dependent hearing loss |
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260 | (1) |
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Sense of sight is based on physics of light |
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261 | (2) |
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Presbyopia can be explained by time-dependent changes in refractive power of lens |
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263 | (1) |
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Terminal differentiation of lens cells leads to formation of cataracts |
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263 | (2) |
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Senses of taste and smell change only slightly with age |
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265 | (1) |
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Changes In Digestive System |
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266 | (7) |
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Time-dependent changes in mouth and esophagus do not impair digestion |
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267 | (1) |
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Decline in stomach function is most often associated with atrophic gastritis |
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268 | (2) |
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Changes in small intestine can affect digestion and nutrient absorption |
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270 | (3) |
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Changes In Urinary System |
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273 | (2) |
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Kidneys remove metabolic waste products from blood |
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273 | (1) |
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Kidneys help regulate blood pressure |
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274 | (1) |
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Renal blood flow and kidney function decline with aging |
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275 | (1) |
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275 | (6) |
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Innate immunity provides first line of defense against infection |
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276 | (1) |
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Acquired immunity relies on lymphocytes reacting to antigens |
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277 | (2) |
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Phagocytotic function of neutrophils and macrophages declines with age |
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279 | (1) |
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Production of naive T cells, number of B cells, and effectiveness of antibodies all decline with age |
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279 | (2) |
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Changes In Reproductive System |
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281 | (3) |
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Menopause is caused by declining secretion of sex hormones by gonads |
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281 | (2) |
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Male fertility declines slightly with age |
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283 | (1) |
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Old age is not barrier to sexual activity |
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284 | (1) |
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284 | (1) |
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285 | (1) |
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286 | (1) |
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287 | (2) |
| Chapter 9 Common Time-Dependent Disease In Humans |
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289 | (56) |
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Nervous System And Neural Signals |
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290 | (7) |
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Nervous system is composed of neurons and supporting cells |
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291 | (1) |
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Membrane potentials establish conditions for neural signal transmission |
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292 | (2) |
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Neurotransmitters chemically link neurons together at synapse |
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294 | (1) |
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Human brain is collection of separate organs and cell types |
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295 | (2) |
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Time-Dependent Diseases Of Human Brain: Alzheimer's And Parkinson's Diseases |
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297 | (15) |
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Changes in structure and neurotransmission seem to be minor in aging brain |
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297 | (1) |
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Amyloid plaques and neurofibrillary tangles accumulate in the aged brain |
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298 | (2) |
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Alzheimer's disease is a time-dependent, nonreversible brain disorder |
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300 | (2) |
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Alzheimer's disease begins in entorhinal cortex and progresses into cortex |
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302 | (1) |
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The E4 allele of the apolipoprotein E gene is risk factor for late-onset Alzheimer's disease |
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303 | (1) |
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Treatments for Alzheimer's disease target neurotransmission and prevention and degradation of amyloid plaques |
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303 | (2) |
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Effective treatments for Alzheimer's disease will require reliable biomarkers |
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305 | (1) |
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Brain imaging techniques serve as biomarkers for LAD |
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306 | (2) |
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Early diagnosis of LAD focuses on detection of MCI and elimination of other dementias |
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308 | (1) |
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Parkinson's disease is associated with loss of dopaminergic neurons |
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308 | (2) |
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Increasing brain's concentration of dopamine is primary objective in treatment of Parkinson's disease |
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310 | (1) |
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Lewy bodies are pathological hallmark of Parkinson's disease |
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310 | (1) |
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Several genes are associated with early onset Parkinson's disease |
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311 | (1) |
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Several factors may predispose individuals to Parkinson's disease |
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311 | (1) |
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Deep brain stimulation can help control movement disorders associated with Parkinson's disease |
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311 | (1) |
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312 | (5) |
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Cardiovascular system is closed system of fluid transport |
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312 | (2) |
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Heart and arteries are excitable tissues |
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314 | (1) |
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Heart controls blood flow and pressure by adjusting cardiac output |
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315 | (1) |
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Principles of fluid dynamics govern overall blood flow |
|
|
316 | (1) |
|
Time-Dependent Diseases Of The Cardiovascular System: Cardiovascular Disease |
|
|
317 | (7) |
|
Environmental factors influence time-dependent decline in cardiovascular system |
|
|
317 | (1) |
|
Arterial plaques can lead to atherosclerosis and ischemic events |
|
|
318 | (2) |
|
Risk factors for atherosclerosis are mixture of genetic and environmental conditions |
|
|
320 | (1) |
|
Statins reduce synthesis of cholesterol in liver and lower serum cholesterol |
|
|
320 | (1) |
|
Hypertension is most common chronic condition in the aged |
|
|
321 | (1) |
|
Heart failure results in decline in cardiac output |
|
|
322 | (1) |
|
Prevalence may be better descriptor of cardiovascular disease than is mortality |
|
|
323 | (1) |
|
Endocrine System And Glucose Regulation |
|
|
324 | (4) |
|
Blood glucose concentration must be maintained within narrow range |
|
|
326 | (1) |
|
Insulin facilitates glucose uptake into liver, muscle, and adipose cells |
|
|
327 | (1) |
|
Time-Dependent Disease Of Endocrine System: Type 2 Diabetes Mellitus |
|
|
328 | (4) |
|
Insulin resistance is a precursor to type 2 diabetes |
|
|
328 | (2) |
|
Type 2 diabetes impairs microvascular blood flow |
|
|
330 | (1) |
|
Altered glucose metabolism may increase cell damage in people with type 2 diabetes |
|
|
330 | (1) |
|
Risk factors for diabetes include increasing age, obesity, and genetic background |
|
|
331 | (1) |
|
Skeletal System And Bone Calcium Metabolism |
|
|
332 | (4) |
|
Parathyroid and thyroid hormones balance blood calcium |
|
|
334 | (1) |
|
Hormones regulate balance between bone mineral deposition and resorption |
|
|
334 | (2) |
|
Time-Dependent Diseases Of Bone: Osteoporosis |
|
|
336 | (4) |
|
Increased rate of bone mineral loss at menopause can lead to osteoporosis |
|
|
337 | (1) |
|
Environmental factors influence risk of developing osteoporosis |
|
|
337 | (2) |
|
Drug therapies can slow bone loss in postmenopausal women |
|
|
339 | (1) |
|
|
|
340 | (1) |
|
|
|
341 | (1) |
|
|
|
342 | (1) |
|
|
|
343 | (2) |
| Chapter 10 Modulating Human Aging And Longevity |
|
345 | (28) |
|
Modulating Biological Aging |
|
|
346 | (2) |
|
Aging cannot be modulated |
|
|
346 | (1) |
|
Mechanisms that lead to loss of molecular fidelity may be modulated in future |
|
|
347 | (1) |
|
Modulating Longevity And Rate Of Aging: Calorie Restriction |
|
|
348 | (8) |
|
Calorie restriction increases life span and slows rate of aging in rodents |
|
|
351 | (3) |
|
Calorie restriction in simple organisms used to investigate genetic and molecular mechanisms |
|
|
354 | (1) |
|
Calorie restriction in nonhuman primates may delay age-related disease |
|
|
355 | (1) |
|
Effectiveness of calorie restriction to extend life span in humans remains unknown and controversial |
|
|
355 | (1) |
|
Modulating Rate Of Aging: Exercise |
|
|
356 | (7) |
|
Definition of exercise for Biology of Aging |
|
|
358 | (1) |
|
Exercise increases muscles' demand for oxygen |
|
|
359 | (2) |
|
Overloading cellular oxidative pathways increases capacity for ATP synthesis |
|
|
361 | (1) |
|
Regular exercise prevents decline in cellular reserve capacity |
|
|
361 | (2) |
|
Changing Definitions Of Health And Aging |
|
|
363 | (5) |
|
World Health Organization's definition of health includes subjective measure of well-being and prospect of complete health |
|
|
364 | (1) |
|
Individual ability to adapt to health circumstances will define health in era of precision medicine |
|
|
365 | (1) |
|
Growing old was once viewed as time of disease, disability, and disengagement from life |
|
|
365 | (1) |
|
Heterogeneity of function within older population led to concept of successful aging |
|
|
366 | (1) |
|
Successful aging includes physical, behavioral, and social components |
|
|
367 | (1) |
|
|
|
368 | (1) |
|
|
|
369 | (1) |
|
|
|
370 | (1) |
|
|
|
371 | (2) |
| Chapter 11 Implications Of An Extended Healthspan |
|
373 | (16) |
|
Achieving The Promise Of Extended Healthspan |
|
|
374 | (7) |
|
Healthspan combines measures of life span and disability |
|
|
374 | (1) |
|
Preventing or curing chronic disease will not continue to reduce disability |
|
|
375 | (1) |
|
Improving healthspan by increasing levels of exercise and reducing caloric intake will be challenging |
|
|
376 | (3) |
|
Prescribable protocols will help to increase participation in exercise and diet treatments |
|
|
379 | (1) |
|
Medical interventions postponing the proximal mechanisms of aging are being developed |
|
|
379 | (2) |
|
Social And Cultural Change In An Aging Society |
|
|
381 | (4) |
|
Healthier and longer life may modify perception of personal achievement and progressive society |
|
|
382 | (1) |
|
Extended longevity and health may change responsibility for renewal of species |
|
|
382 | (2) |
|
Low birth rates and extended longevity may alter current life cycle of generations |
|
|
384 | (1) |
|
|
|
385 | (1) |
|
|
|
385 | (2) |
|
|
|
387 | (1) |
|
|
|
388 | (1) |
| Appendix: US Life Table Calculations |
|
389 | (8) |
| Glossary |
|
397 | (24) |
| Index |
|
421 | |
