Longevity: The Biology and Demography of Life Span

By James R. Carey

Despite our deep interest in mortality, little is known about why some individuals live to middle age and others to extreme old age. Life span, mortality, and aging present some of the most profound mysteries in biology. In Longevity, James Carey draws on unprecedented data to develop a biological and demographic framework for identifying the key factors that govern aging, life span, and mortality in humans and other animals.


Carey presents the results of a monumental, twelve-year, National Institute on Aging-funded research project on the determinants of longevity using data from the life tables of five million Mediterranean fruit flies, the most comprehensive set of life table studies ever on the mortality dynamics of a single species. He interprets the fruit fly data within the context of human aging and the aging process in general to identify the determinants of mortality. Three key themes emerge: the absence of species-specific life span limits, the context-specific nature of the mortality rate, and biodemographic linkages between longevity and reproduction.


A powerful foundation for the emerging field of biodemography and a rich framework for considering the future of human life span, Longevity will be an indispensable resource for readers from a range of fields including population biology, demography, gerontology, ecology, evolutionary biology, and medical research.

• Language: English
• Publisher: Princeton University Press
• Release date: Jan 12, 2021
• ISBN: 9780691224084

Book preview

LONGEVITY

LONGEVITY

THE BIOLOGY AND DEMOGRAPHY

OF LIFE SPAN

James R. Carey

PRINCETON UNIVERSITY PRESS PRINCETON AND OXFORD

Copyright © 2003 by Princeton University Press

Published by Princeton University Press, 41 William Street,

Princeton, New Jersey 08540

In the United Kingdom: Princeton University Press, 3 Market Place,

Woodstock, Oxfordshire OX20 1SY

All Rights Reserved

Library of Congress Cataloging-in-Publication Data

Carey, James R.

Longevity : the biology and demography of life span / by James R. Carey.

p. cm.

Includes bibliographical references (p. ).

ISBN 0-691-08848-9 (alk. paper)—ISBN 0-691-08849-7 (pbk. : alk. paper)

eISBN: 978-0-69122-408-4 (ebook)

1. Longevity. I. Title.

QP85 .C283 2002

612.6'7—dc21 2002025294

British Library Cataloging-in-Publication Data is available

https://press.princeton.edu/

R0

DEDICATED TO MY CHILDREN

Bryce, Ian, and Meradith_______

FOR THEIR STRENGTH OF CHARACTER

". . . we find less talk of life as an exercise in

endurance, and of death in a hopeless cause;

and we hear more of life as a seeking and a

journeying. "

—R. W. SOUTHERN

Contents

List of Figures  xiii

List of Tables  xvii

Preface and Acknowledgments  xix

Permissions  xxiii

1. Introduction  1

1.1. The Problem  1

1.2. The Epistemological Framework  2

1.2.1. Mortality and Aging as Fundamental Processes  2

1.2.2. Model Systems and Actuarial Patterns  3

1.3. Importance of Scale  3

1.3.1. Historical Background  3

1.3.2. Large-scale Medfly Life Tables  4

1.3.3. Experimental Principles  5

1.3.4. Overview of the Medfly Mortality Database  5

1.4. Overarching Themes  7

1.5. Organization of the Book  8

2. Operational Framework  10

2.1. Background  10

2.1.1. The Mediterranean Fruit Fly  10

2.1.2. Medfly as a Model Species  10

2.1.3. The Moscamed Mass-rearing Facility  11

2.2. Empirical Methods  11

2.2.1. Cages  11

2.2.2. Adult Rearing  12

2.2.3. General Experimental Procedure  13

2.3. Analytical Methods  13

2.3.1. The Life Table  13

2.3.2. Life Table Construction and Interpretation  14

2.3.3. Additional Life Table Parameters and Relationships  14

2.3.4. The Mortality Function and Its Importance  20

2.3.5. The Force of Mortality  21

2.3.6. Smoothing Age-specific Mortality Rates  22

2.3.7. The Gompertz Model  23

2.3.8. Below-threshold Mortality  23

2.3.9. Peak-aligned Averaging  24

2.4. Summary  25

3. Mortality Deceleration  27

3.1. Background  27

3.2. Slowing of Mortality at Older Ages  28

3.3. Implications of Mortality Deceleration  33

3.4. Demographic Selection  34

3.4.1. Background and Concept  35

3.4.2. Explaining Mortality Patterns  35

3.4.3. Epistemological Concepts of Demographic Selection  37

3.5. Sex Differentials  37

3.5.1. Background  38

3.5.2. Mortality Trajectories  39

3.5.3. Medfly Mortality in Solitary Confinement  42

3.5.4. Cohort Variability  42

3.5.5. Sex Mortality Crossover  42

3.5.6. A General Framework  49

3.6. Summary  51

4. Reproduction and Behavior  53

4.1. Reproduction and Longevity: Visualizing Linkages  53

4.1.1. Graphic Concept—Event History Diagrams  53

4.1.2. Application to Medfly Reproduction  54

4.1.3. Insights from Graphs  54

4.1.4. Implications  57

4.2. Relationship of Reproduction and Mortality  59

4.2.1. Empirical Framework  60

4.2.2. Basic Birth and Death Rates  60

4.2.3. Bimodal Distribution of Deaths for Infertile Females  64

4.2.4. Age Patterns of Lifetime Reproduction  65

4.2.5. Implications  68

4.3. Cost of Virginity  70

4.3.1. Operational Framework  70

4.3.2. Sex-specific Survival of Virgins  71

4.3.3. Mortality Crossovers  74

4.3.4. Implications  75

4.4. Supine Behavior—a Predictor of Time-to-death  77

4.4.1. Background  77

4.4.2. Empirical and Statistical Framework  78

4.4.3. Results  79

4.4.4. Implications  83

4.5. Summary  84

5. Mortality Dynamics of Density  86

5.1. Background  86

5.2. Operational Framework  88

5.2.1. Types of Density Effects  88

5.2.2. Experimental Details  88

5.2.3. Age-Density Models  89

5.3. Mortality Dynamics  91

5.3.1. Density Effects on Survival and Life Expectancy  91

5.3.2. Effects of Initial Density on Mortality  93

5.3.3. Effects of Initial Density on Mortality Patterns  94

5.3.4. Correlation of Density and Mortality  97

5.3.5. Density Effects on Sex Survival Ratios  98

5.3.6. Equivalent Current Densities  101

5.3.7. Regression Model  104

5.4. Implications  107

5.4.1. Medfly Mortality Patterns at Older Ages  107

5.4.2. Density in Human Context  109

5.5. Summary  109

6. Dietary Effects  111

6.1. Early Mortality Surge in Protein-deprived Females  111

6.1.1. Reversal of Life-expectancy Sex Differential  112

6.1.2. Hazard Rates and Early Surge in Mortality  112

6.1.3. Vulnerable Periods  114

6.1.4. Implications and Conclusions  116

6.2. Female Sensitivity Underlies Sex Mortality Differential 118

6.2.1. Experimental Framework  118

6.2.2. Sex-specific Life Expectancy  119

6.2.3. Sex Differences in Mortality Trajectories  121

6.2.4. Mean Sex-mortality Trajectories  123

6.2.5. Relative Cost of Reproduction in Females  125

6.2.6. Implications  125

6.2.7. Conclusions  127

6.3. Mortality Oscillations Induced by Periodic Starvation 127

6.3.1. Experimental Framework  128

6.3.2. Statistical Summary  128

6.3.3. Treatment Effects on Longevity  130

6.3.4. Interactions  130

6.3.5. Within-cycle Distributions of Deaths  134

6.3.6. Mortality Patterns and Oscillations  135

6.3.7. Implications and Conclusions  140

6.4. Summary  142

7. Linkages between Reproduction and Longevity  143

7.1. Dual Modes of Aging  143

7.1.1. Hypothesis  143

7.1.2. Life Expectancies  144

7.1.3. Reproduction  146

7.1.4. Mortality Trajectories  146

7.1.5. Implications  150

7.2. Reproductive Clock  150

7.2.1. Constant Rate of Egg-laying Decline  151

7.2.2. Mortality and Exhaustion of Reproductive Potential  153

7.2.3. Confirming the Association between Reproductive Potential and Longevity  153

7.2.4. Graphical Confirmation of the Association  154

7.2.5. Exchanging Lifetimes between Flies in Randomly Selected Pairs  154

7.2.6. Predicted Subsequent Egg Laying  156

7.2.7. Discussion and Implications  156

7.3. Food Pulses  157

7.3.1. Experimental Methods  159

7.3.2. Descriptive Statistics  160

7.3.3. Cohort Survival  160

7.3.4. Age Patterns of Reproduction  162

7.3.5. Within-cycle Reproductive Patterns  165

7.3.6. Modeling Relationships and Graphical Analysis  168

7.3.7. Discussion and Implications  171

7.4. Summary  174

8. General Biodemographic Principles  176

8.1. Why Biological Data Is Important for Deriving General Principles  176

8.2. Principles of Senescence 177

8.2.1. All Sexual Organisms Senesce  177

8.2.2. Natural Selection Shapes Senescence Rate  178

8.3. Principles of Mortality  178

8.3.1. Biological Organisms Die Whereas Mechanical Systems Fail  179

8.3.2. Mortality Decelerates at Advanced Ages  180

8.3.3. Mortality Is Sex-specific  180

8.3.4. Mortality Trajectories Are Facultative  181

8.3.5. Selection Shapes Mortality Trajectories  181

8.3.6. Mortality Rates Are Undetectable below 1/n  182

8.3.7. Mortality Variance Increases with Cohort Age  182

8.4. Principles of Longevity  183

8.4.1. Longevity Is Adaptive  184

8.4.2. Maximal Age Is Influenced by Sample Size  184

8.4.3. Life Span Is Indeterminate  186

8.4.4. Reproduction Is a Fundamental Longevity Determinant 186

8.4.5. The Heritability of Individual Life Span Is Small  187

8.5. Biodemographic Principles and the Human Primate  187

8.5.1. Body and Brain Size Predict Extended Human Longevity 188

8.5.2. Long-lived Monkeys Have Life Spans Proportional to Human Centenarians  189

8.5.3. Post-reproduction Expected from Primate Patterns  189

8.6. Biodemography of Human Development, Reproduction, and Genetics  190

8.6.1. Developmental Stages and Mortality  190

8.6.2. The Cost of Reproduction in Women  192

8.6.3. Extreme Longevity in Families and Close Kin  194

8.7. Proximate Determinants of Human Longevity  196

8.7.1. Socioeconomic Factors  196

8.7.2. Physical Fitness, Exercise, and Nutrition  197

8.7.3. Behavioral Factors: Smoking and Alcohol Use  197

8.8. Longevity Gains Are Self-reinforcing  198

8.9. Summary  198

9. A General Theory of Longevity  200

9.1. Comparative Demography of Longevity  201

9.1.1. A General Classification Scheme  201

9.1.2. Evolution of Extended Longevity in Wasps: The Interactive Role of Sociality  202

9.2. Foundational Principles  206

9.2.1. Principle #1: Evolutionary Theory of Aging  206

9.2.2. Principle #2: Intergenerational Transfers  207

9.2.3. Principle #3: Division of Labor  207

9.3. Model of Longevity Extension  208

9.3.1. Reduced Infant Mortality  208

9.3.2. Demographic Transition  209

9.3.3. Improvement in Parental Health and Survival  210

9.3.4. Increase in Offspring Quality  210

9.3.5. Incremental Increase in Longevity as Cause and Consequence  211

9.4. Model Application  212

9.4.1. Human Longevity in Biodemographic Context  212

9.4.2. Primate Origins of Longevity Extension  213

9.4.3. Prehistoric and Historical Patterns of Longevity Change  215

9.4.4. Health, Wealth, and Longevity  216

9.5. Implications of Longevity-oriented Theory  216

9.6. Human Life Span Extension: A Framework for the Future  218

9.7. Summary  219

10. Epilogue: A Conceptual Overview of Life Span  221

10.1. Background  221

10.2. Abstract Perspectives  222

10.3. Death and Extinction  223

10.4. Boundary and Perpetuity  224

10.5. Evolution  224

10.5.1. Evolutionary Origins of Senescence  224

10.5.2. Life Span as an Evolutionary Adaptation  225

10.5.3. Evolutionary Ecology of Life Span  225

10.6. Roles of the Elderly  231

10.7. Minimal Life Spans  231

10.8. Absence of Life Span Limits  232

10.9. Humans  233

10.9.1. Life-Span Patterns: Humans as Primates  233

10.9.2. Sex Life-Span Differentials  234

10.9.3. Age Classification  235

10.10. Theory of Longevity Extension in Social Species: A Self-reinforcing Process  237

10.11. Future  238

10.12. Scientific and Biomedical Determinants  239

10.13. Demographic Ontogeny  241

10.13.1. Individuals  241

10.13.2. Societies  241

10.14. Postscript  243

Bibliography  245

Index  271

Figures

2.1. Schematic diagram of the threshold-mortality concept redrawn from Promislow et al. 1999.

3.1. Age-specific mortality rates for 3 experiments.

3.2. Smoothed age-specific mortality rates for 3 medfly mortality experiments plotted on a linear scale.

3.3. Distribution of the estimated slopes of the logarithms of age-specific mortality at 10, 30, and 45 days in each of 167 medfly cages with an average initial density of 7,200 adults (experiment 3).

3.4. Age-specific mortality rates computed for cohorts of 6 different initial numbers from n = 25 to n = 100,000.

3.5. Results of frailty model with 12 subpopulations and with a composite cohort.

3.6. Smoothed male and female age-specific mortality rates from cohorts consisting of approximately 600,000 medflies of each sex.

3.7. Sex mortality ratios for medflies (male to female age-specific mortality ratios) using the smoothed rates shown in figure 3.6 and the survival sex ratio (ratio of male to female survival schedules).

3.8. Mortality and survival sex ratios for medflies reared in solitary confinement.

3.9. Male versus female mortality rates at 10 and 30 days for 167 medfly cohorts of approximately 3,600 individuals of each sex.

3.10. Male versus female expectations of remaining life at 0 and 30 days for 167 medfly cohorts of approximately 3,600 individuals of each sex.

3.11. Ages of the last male and the last female to die in each of 167 medfly cohorts of approximately 3,600 individuals of each sex.

4.1. Graphic depicting age-specific cohort survival and lifetime reproduction for 1,000 individual Mediterranean fruit fly females.

4.2. Frequency distribution of the level of daily egg laying (> 0) in 1,000 medfly females over 3 age periods relative to the total number of oviposition-days within the period.

4.3. Relationship between cumulative egg production in female medflies through 30 days and the total number of eggs each subsequently produced.

4.4. Relationship between cumulative egg production in female medflies through 30 days and remaining life span.

4.5. Lifetime reproduction vs. life span in 1,000 medfly females.

4.6. Trajectories of age-specific mortality based on 1,000 individual medfly females.

4.7. Distribution of deaths in females that laid no eggs and fertile females.

4.8. Smoothed 3-D plot showing the relationship between the age-specific reproduction of females rank-ordered from high to low lifetime reproduction.

4.9. Cross section of surface plot shown in figure 4.8 for the Mediterranean fruit fly at 4 levels of lifetime egg production.

4.10. Smoothed hazard rates for 33 female Mediterranean fruit fly cohorts maintained in either all-female or mixed-sex cages.

4.11. Mean hazard rates for the 33 female Mediterranean fruit fly cohorts shown in figure 4.10.

4.12. Event history charts for supine behavior in 203 male medflies relative to cohort survival.

4.13. Smoothed plots for the supine number recorded in the 2-hour observation period of each of 203 males aligned relative to time of death.

4.14. Schedules of remaining life expectancy for male medflies for the cohort as a whole as well for males both prior to and after the onset of supine behavior.

4.15. Schedules of active life and total survival for the male medfly cohort.

5.1. Survival in a hypothetical cohort showing 3 types of densities.

5.2. Smoothed age-specific mortality for male and female medflies at 3 different initial densities.

5.3. Geometric rate of change in age-specific mortality for male and female medflies at 3 different initial densities.

5.4. Relationship between initial density and cumulative density for medfly density experiments.

5.5. Correlation coefficients for cumulative and current density vs. mortality at each age for male and female medflies.

5.6. Ratio of the sex-specific survival schedules for the low- vs. the high-density experiments.

5.7. Ratio of the male medfly survival schedule to the female medfly survival schedule for each of the 3 initial cage densities.

5.8. Daily age-specific death rates at specified densities for (A) the density experiment and (B) the density experiment and original 1.2 million medfly experiment combined.

5.9. Composite of age-specific death rates for (A) the density experiment and (B) the density experiment and original 1.2 million medfly experiment combined.

6.1. Estimated hazard rates for 4 groups of medflies.

6.2. Estimated hazard rates obtained separately for each of 132 cohorts of medflies.

6.3. Peak-aligned estimated hazard rates from 0 to 25 days.

6.4. Smoothed hazard rates for 35 male Mediterranean fruit fly cohorts in each of 4 treatments.

6.5. Smoothed hazard rates for 35 female Mediterranean fruit fly cohorts in each of 4 treatments.

6.6. Mean hazard rates for the 35 male and female Mediterranean fruit fly cohorts shown in figures 6.4. and 6.5.

6.7. Relationship between female and male life expectancy in all treatment cohorts for sugar-only and full-diet treatments.

6.8. Interaction plots for mean lifetime response in medfly diet experiments.

6.9. Hazard rates response of female and of male medfly cohorts with access to either sugar-only or full diets in 1-of-3 different cyclical patterns or control.

6.10. Log mean amplitudes measuring the oscillations in life table data shown for all cohorts.

7.1. Age-specific schedule of reproduction for female medflies maintained on a sugar-only diet, on a full diet (sugar + protein hydrolysate) throughout their lives, or on a sugar diet from eclosion and then switched to a full diet on days, 30, 60, and 90.

7.2. Event history diagrams for survival and reproduction in the 5 cohorts of 100 females.

7.3. Smoothed age-specific probabilities of death for the 5 study cohorts starting at the time when they were first switched from sugar to a full diet.

7.4. Trajectories of fecundity and mortality.

7.5. Lifetime and proportion of eggs left.

7.6. Survival schedules for flies in each of the 7 treatments and 3 controls.

7.7. Average number of eggs/female/day in the medfly study consisting of 7 treatments and 3 control cohorts.

7.8. Event history graphs of individual female reproduction in each of the 10 treatments.

7.9. Patterns of egg production for composite egg-laying cycles averaged over the life course of all flies.

7.10. Relationship of lifetime egg production (response) and the predictors of female longevity, age of initial peak of egg production, and the height of the initial egg-laying peak

8.1. Summary chart of all longevity data contained in Longevity Records: Life Spans of Mammals, Birds, Reptiles, Amphibians and Fish by Carey and Judge (2000a).

8.2. Observed and predicted record life spans for Old World primate genera.

8.3. Relationship between human growth rate and stage-specific mortality.

8.4. Event history reproductive chart for 500 randomly selected French-Canadian women rank-ordered by longevity after age 13.

9.1. Relative life span for 9 mammalian orders.

9.2. Record captive life spans by body size for primate genera.

10.1. Schematic of sexual reproduction in the protozoan Paramecium aurelia (redrawn from Clark 1996, p. 70).

10.2. Three long-lived animal species or groups that likely achieved their extended life span due to direct natural selection.

10.3. The ant queen, a eusocial insect.

10.4. The life cycle of the mayfly.

10.5. Predicted life spans of different hominoid species based on anthropoid subfamily values for body and brain mass regressions.

10.6. Examples of how the timing and duration of different life-course events may change with increasing longevity.

Tables

1.1. Large-scale mortality studies on Mediterranean fruit fly and other tephritid fruit flies or parasitoid.

2.1. Main life table functions.

2.2. Life table parameters for Mediterranean fruit fly.

2.3. Selected mortality parameters and formulae, change indicators, and scaling models.

3.1. Number alive, age (days), and remaining life expectancy of medflies in each of 3 experiments.

3.2. Values of frailty z and proportions of flies at each level of frailty for the Gompertz model.

4.1. Number of female Mediterranean fruit flies alive at age x and fraction of initial number surviving to age x for cohorts maintained in either all-female or mixed-sex cages.

4.2. Number of female Mediterranean fruit flies alive at age x (for x > 30) and survival (lx) normalized using number alive at 30 days for cohorts maintained in either all-female or mixed-sex cages.

4.3. Table of pair-wise comparisons for log-transformed remaining lifetimes for groups of virgin and mated medflies.

5.1. Summary of results for male and female medflies maintained in mixed cages at three initial densities—2,500, 5,000, and 10,000 flies per cage.

5.2. Average mortality ratio (SD) by sex for 3 density experiments from day 0 through 40.

5.3. Summary statistics for analysis of medfly cage density effects on mortality.

5.4. Correlation between the number of deaths before and after age x for 2 medfly experiments alone and combined.

6.1. Life expectancies at eclosion in days for male and female medflies.

6.2. Expectation of life in days (e0), standard deviation (SD), and number of cages (n) for male and female medflies subjected to 4 different treatments.

6.3. MANOVA table for mean lifetimes, subject to different diets and irradiation treatments.

6.4. Results on treatment effects of diet and fertility separated by sex.

6.5. Average of the expectations of life at eclosion (e0) in days and standard deviations (SD) for 13 cohorts of medflies subjected to 1-of-3 different cycles of food availability and l-of-2 different diets.

6.6. ANOVA table for mean lifetimes by sex in the medfly subject to different diets and starvation schemes.

6.7. Number of deaths by sex on days when food was present (food-days) and not present (non-food days) and the percent of all deaths on non-food days.

6.8. Percent of total deaths that occurred in experimental cohorts at different stages of the food deprivation cycle.

6.9. Means and standard deviations (SD) for log amplitudes of hazard rate oscillations by sex for intact or irradiated medflies maintained on l-of-2 diets.

6.10. ANOVA table for mean log amplitudes of the hazard rate oscillations by sex in the medfly subject to different diets and starvation schemes.

7.1. Longevity and reproductive data for medfly cohorts given access to a full diet at different ages.

7.2. Life expectancy and lifetime reproduction (eggs/female) for medfly cohorts subject to different food cycles.

7.3. Mean and standard error for first egg peak and its location (age).

8.1. Heritability of life spans.

9.1. Categories of factors that favor the evolution of extended life span in insects, arachnids, and vertebrates: selected examples species or groups.

9.2. Evolutionary changes in wasp longevity and social complexity.

9.3. Evolved life span of ancestral hominids and modern humans.

Preface and Acknowledgments

THE SEEDS for the research upon which much of this book is based were sown at a National Institute on Aging (NIA)-sponsored workshop titled Upper Limits to Human Life Span held at the University of California, Berkeley, in March 1987. One of the most important issues that emerged from this workshop was the paucity of information in the literature on actuarial aging (i.e., life table data) on nonhuman species: despite the thousands of life tables in the ecology and gerontology literature, the vast majority were based on a few score or a few hundred individuals. These small initial numbers thus provided virtually no information on mortality rates at older ages in any species. Immediately after this workshop James Vaupel (who had also attended it) and I agreed to explore the possibility of collaborating on a project designed to construct a large-scale life table of the Mediterranean fruit fly, a species that is reared in vast numbers at Moscamed, a medfly factory near Tapachula, Mexico. The director at that time was one of my former Ph.D. students, Pablo Liedo. A year after the idea for this large-scale life-table study was conceived we submitted a proposal to NIA as part of a larger program project (headed by James Vaupel). This program was subsequently funded, and the preliminary results were reported in a News and Review article in Science magazine (Barinaga 1992). A formal paper was published in 1992 titled Slowing of mortality at older ages (Carey, Liedo, Orozco, and Vaupel 1992; see also companion paper by Curtsinger et al. 1992). This set the stage for a subsequent funding cycle and a series of new research questions.

The second funding cycle of the program project began in 1994 and focused initially on concerns that were raised in Letters to the Editor in Science (Kowald and Kirkwood 1993; Nusbaum et al. 1993; Robine and Ritchie 1993; Olshansky et al. 1993; Gavrilov and Gavrilova 1991), most notably whether deceleration was due to density effects, whether the phenomenon was general and thus observed in other species, and if medflies subjected to a wide range of different environmental manipulations would also exhibit mortality deceleration at older ages. Later in this 5-year funding cycle (mid-1990s) we began to shift emphasis from life table studies involving tens or hundreds of thousands of flies in group cages to experiments involving the mortality and daily reproduction of individual flies. At that time we also began efforts at constructing a large database on the record life spans of vertebrates. The project was funded for third cycle starting in 1999 and therefore, the medfly life table project is in the 13th year of continued funding.

There are several reasons why I am hopeful that the proposed book will contribute new knowledge to the biology of aging and the biodemography of life span. First, the book reflects the overall continuity of the project from inception to present. Indeed, it is the first nonedited book on the biology of aging and longevity that focuses on a single-model system in which the experiments were designed by the same group of core scientists (i.e., myself, Vaupel, Liedo, and other key colleagues), in which the data were gathered in the same laboratory by essentially the same group of technicians (with very little turnover), and in which the results were analyzed, written up, and published quickly in uniformly high-quality journals.

Second, the overall data set on which the collective studies described in the book are based is truly unprecedented. The complete database currently consists of age- and sex-specific mortality data for over 5.6 million individuals (i.e., data quantity) in which the same types of cages, larval and adult food, physical conditions, and collection procedures were used from the beginning of the studies in 1989 to the present (i.e., data quality).

Third, the science of aging is such a rapidly moving field that knowledge of many aspects in the medfly system described in this book—including experimental designs, interpretation of results, and summaries and syntheses—may be helpful for studies using other model systems (e.g., nematode, Drosophila, yeast, rodents). In particular, the results presented in the book will sharpen the experimental focus and frame the thinking of researchers who use more costly vertebrate systems.

Fourth, the book will serve as an introduction to experimental demography and biodemography for a wide range of biologists not specializing in aging science (e.g., ecologists, population biologists, demographers, actuaries). There appears to be no other source of advanced concepts in life table and mortality analysis for biologists, and I am unaware of any ecology text that goes much beyond elementary life table analysis.

Fifth, the book contains several new syntheses including (i) biodemographic principles that capture the general concepts such as slowing of mortality, male-female mortality differentials, and the indeterminacy of life span; (ii) analytical models that make explicit the relationship between life history traits such as reproduction and longevity or mortality; and (iii) longevity theory that outlines a general model in social organisms describing how longevity extension coevolves with sociality. My focus at the end of the book is primarily on human longevity.

Sixth, the book contains studies that were motivated as much by the conventional hypothesis-driven questions (tests of specific hypotheses such as upper life-span limits) as by discovery-driven science, which was first characterized in the context of genome research (Aebersold et al. 2000; Idelker et al. 2001) but which I believe applies equally well to some of the research described in this book. Indeed, one of the most exciting outcomes of using huge initial numbers in life table studies was the discovery of nuances in mortality trajectories at both young and old ages that then required hypothesis testing. It is discovery science because the research involves unknown biological and demography territory.

Much of the writing for this book was done over the past ten years in the form of refereed, coauthored publications. This series of research papers started with the 1.2 million medfly life table study (Carey et al. 1992) and ended with a paper containing a conceptual overview of life span (chapter 10) that I initially presented at the workshop Life Span: Evolutionary, Ecological and Demographic Perspectives held in Santorini, Greece, in May 2001. The final version of the article that became chapter 10 was not completed until early 2002 (Carey 2003). The book organization and content reflect the progression of ideas and the evolution of concepts that emerged from my thinking about the determinants of mortality, survival, and life span over these years. One of the most influential articles that shaped my thinking about the integration of longevity and mortality concepts was by the late gerontologist George Sacher (1978), Longevity and aging in vertebrate evolution. In this paper Sacher introduced the concept of the biology of the finitude—a triad consisting of the biology of life span, aging, and death. In my mind this finitude idea provides conceptual continuity by framing life span in a functional (life history) context, aging in a mechanistic context, and death in a finality context. Thus the concept introduced in the Sacher article helped me to integrate different sections of the book—the results of studies on mortality dynamics presented in chapters 3-7 are woven into many of the general biodemographic principles presented in chapter 8, which, in turn, are used as a foundation to develop theories and concepts on longevity and life span presented in chapters 9-10. In other words, Sacher’s ideas provide a bridge between the allied but different conceptual domains of mortality, longevity, and life span (I consider the biology of death in this book in the final chapter only briefly; however, this neglected area is ripe for development of a stand-alone research program in aging).

I thank members of Duke University-based, NIA-funded program project (originally titled Oldest-old Mortality and directed by James Vaupel) including Kaare Christensen, James Curtsinger, Lawrence Harshman, Aziz Khazaeli, Valter Longo, Kenneth Manton, Cynthia Owens, Linda Partridge, Deborah Roach, Marc Tatar, and Anatoli Yashin for their input over the past decade and especially for their friendship. I am particularly grateful to Pablo Liedo for the important role he played as the senior scientist and collaborator in Tapachula; to both Jane-Ling Wang and Hans Müller for their statistical help and remarkable insights; to Debra Judge for her superb contributions as coauthor of several key papers on the principles of biodemography (chapter 8) and the general theory of longevity (chapter 9); and to Nikos Papadopoulos for the huge job of collating and reformatting the scores of figures ineluded in the book. I express my deep appreciation to Robert Arking and Marc Mangel for taking the time to read and critique the entire book manuscript and to the many colleagues with whom I coauthored papers used in this book, including William Capra, J.-M. Chiou, Byron Katsoyannos, Nikos Kouloussis, Xieli Liu, Brad Love, Dina Orozco, Nikos Papadopoulos, Scott Pletcher, Daniel Promislow, D. Wu, Zhang Yi, and Ying Zhang. I thank my colleagues at the UC Berkeley Center for the Economics and Demography of Aging for their insights and inspiration throughout the years, including Ronald Lee, John Wilmoth, Shripad Tuljapurkar, and especially Kenneth Wachter for his interest and support from the very beginning of the program project. I also deeply appreciate the strong support of both Rose Li and Richard Suzman and the research funding from the National Institute on Aging. I thank Linda Truilo for her meticulous and thorough editing. Lastly, it is a pleasure to acknowledge with gratitude the encouragement and patience of Samuel Elworthy at Princeton University Press. I thank them all, truly.

Although I was lead author and writer on most of the research papers used in this book, James Vaupel (JV) and Hans Müller (HM) were the lead authors and writers of four papers from which substantial portions were used, including section 3.4 on demographic selection (JV), several subsections on modeling in chapter 5 on density effects (JV), section 6.1 on early mortality surge (HM), and section 7.2 on reproductive clock (HM).

James Vaupel has provided input at all levels and has made a difference in how I approach demography in particular and science in general. This book could not have been written had he not taken interest in the program project, recognized the potential of the medfly as a model system, and provided intellectual stimulation and camaraderie. I owe my greatest thanks to him.

Permissions

Section 2.2 reprinted from: Carey, J. R. and Liedo, P. 1999. Measuring mortality and reproduction in large cohorts of the Mediterranean fruit fly, in: H. Sternberg and P. S. Timiras (ed.), Studies of Aging, pp. 111-124, Berlin: Springer-Verlag, Copyright © 1999 with permission from Springer-Verlag.

Section 2.3 reprinted from: Carey, J. R. 1999. Population study of mortality and longevity with Gompertzian analysis, in: B. P. Yu (ed.), Methods in Aging Research, pp. 3-24, Boca Raton: CRC Press, Copyright © 1999 with permission from CRC Press, and Carey, J. R. 2001. Insect biodemography. Annual Review of Entomology 46:79-110, Copyright © 2001 with permission from Annual Reviews, Inc.

Section 3.2 reprinted from: Carey, J. R., Liedo, P., Orozco, D., and Vaupel, J. W. 1992. Slowing of mortality rates at older ages in large medfly cohorts. Science 258:457-461, Copyright © 1992 with permission from the American Association for the Advancement of Science.

Section 3.4 reprinted from: Vaupel, J. W. and Carey, J. R. 1993. Compositional interpretations of medfly mortality. Science 260:1666-1667, Copyright © 1993 with permission from the American Association for the Advancement of Science.

Section 3.5 from: Carey, J. R. and Liedo, P. 1995. Sex-specific life table aging rates in large medfly cohorts. Experimental Gerontology 30:315-325, Copyright © 1995 with permission from Elsevier Science, and Carey, J. R., Liedo, P., Orozco, D., Tatar, M., and Vaupel, J. W. 1995. A male-female longevity paradox in medfly cohorts. Journal of Animal Ecology 64:107–116, Copyright © 1995 with permission from Blackwell Publishing.

Section 4.1 reprinted from: Carey, J. R., Liedo, P., Müller, H.-G., Wang, J.-L., and Vaupel, J. W. 1998. A simple graphical technique for displaying individual fertility data and cohort survival: case study of 1000 Mediterranean fruit fly females. Functional Ecology 12:359-363, Copyright © 1998 with permission from Blackwell Publishing.

Section 4.2 reprinted from: Carey, J. R., Liedo, P., Müller, H.-G., Wang, J.-L., and Chiou, J.-M. 1998. Relationship of age patterns of fecundity to mortality, longevity, and lifetime reproduction in a large cohort of Mediterranean fruit fly females. Journal of Gerontology: Biological Sciences 53A:B245-B251, Copyright © 1998 The Gerontological Society of America. Reproduced