Handbook of the Biology of Aging, Seventh Edition (Handbooks of Aging)

The Handbook of the Biology of Aging, 7e, is 100% revised from the 6th edition. Providing a comprehensive synthesis and review of the latest research findings in the biology of aging, it is intended as a summary for researchers, and is also suitable as a high level textbook for graduate and upper level undergraduate courses. The 7th edition is organized into two main sections, first covering the basic aging processes and then the medical physiology of aging. This puts less emphasis on research germane only to specific species and more emphasis on the mechanisms that affect aging across species, and what this means medically for the aging of humans. This volume allows basic researchers to keep abreast of basic research outside their subdiscipline as well as recent clinical findings, while allowing medical, behavioral, and social gerontologists to understand what basic scientists and clinicians are discovering. Coverage of basic aging processes includes the effects of dietary restriction, somatotropic axis, free radicals, apoptosis, adipose tissue, stem cells, leukocyte telomere dynamics, genetics, sirtuins, inflammation, and protein homeostasis on aging. Coverage of the medical physiology of aging includes several chapters on aging effects on the human brain including changes in brain myelination, cerebral microvasculature, and cerebral vascular dysfunction. Additional chapters include research on aging pulmonary function, insulin secretion, thermoreception and thermoregulation, calorie restriction, frailty & mortality, and sex differences in longevity and aging. This more clinically-oriented section advances our understanding of what to expect, how to prevent, and how to treat common medical effects of aging. The Handbook of the Biology of Aging, 7e is part of the Handbooks of Aging series, including Handbook of the Psychology of Aging and Handbook of Aging and the Social Sciences, also in their 7th editions. Contains basic aging processes as determined by animal research as well as medical physiology of aging as known in humansCovers hot areas of research, like stem cells, integrated with longstanding areas of interest in aging like telomeres, mitochondrial function, etc.Edited by one of the fathers of gerontology (Masoro) and contributors represent top scholars in gerintology Cover......Page 1 Book......Page 2 Front matter......Page 4 Copyright......Page 5 Contributors......Page 6 Foreword......Page 9 Preface......Page 11 About the Editors......Page 13 Introduction......Page 14 DR Regimens in C. elegans......Page 15 Criteria......Page 16 Energy Sensors: Insulin–PI3K, SIR2, AMPK, TOR......Page 20 Transcriptional Regulators: FoxO/daf-16, FoxA/pha-4, NFE2/skn-1, HIF-1,HSF-1, CBP-1......Page 21 Fly DR: SIR2, TOR, and FoxO......Page 23 DR in Mammals: SIR2, TOR, Insulin–FoxO, NFE2......Page 24 Type of Nutrients......Page 25 Tissue Specificity......Page 26 DR Mimetics......Page 27 References......Page 28 Introduction......Page 35 Body size and composition......Page 36 Glucose metabolism and insulin sensitivity......Page 37 Oxidative metabolism and related factors of stress resistance......Page 38 Cognitive function......Page 40 Immune function......Page 42 Age-related pathology and neoplasia......Page 44 References......Page 45 Introduction......Page 56 Complex I ROS Production......Page 57 Complex III Inhibitors......Page 59 Electron Transfer Flavoprotein–Ubiquinone Oxidoreductase (ETF–Q Oxidoreductase)......Page 60 Mitochondrial antioxidant systems......Page 61 Free radical theories of aging......Page 63 Conclusions......Page 65 References......Page 66 Aging and Apoptosis in Muscle......Page 71 Myonuclear Apoptosis......Page 72 Myonuclear Apoptotic Signaling in Skeletal Muscle......Page 73 Cellular Conditions for Activation of the Intrinsic Apoptotic Pathway......Page 74 Mitochondrial Bioenergetics in Aging Muscle......Page 75 Mitochondrial Permeability......Page 76 Oxidative Stress and Mitochondria......Page 77 The BCL-2 Protein Family......Page 78 Caspase-Independent Signaling......Page 79 Mitochondria-Mediated Signaling for Apoptosis in Sarcopenia......Page 80 TNF- and Death Receptor Signaling......Page 85 Cross Talk between Extrinsic and Intrinsic Apoptotic Signaling......Page 89 Cellular Conditions that Activate the SR/ER–Ca2 Stress Apoptotic Pathway......Page 90 Signaling via the SR–Ca2+ Stress Apoptotic Pathway......Page 91 The Role of MyoD in Apoptosis of MPCs......Page 92 Interventions by Muscle Loading......Page 93 Unloading and Disuse in Skeletal Muscle......Page 102 Regulation of Apoptosis by Aerobic Exercise......Page 103 Aging and cardiomyocyte apoptosis......Page 104 Apoptosis and the Aging Heart......Page 105 Modulation of Bcl-2 and Bax in the Aging Heart......Page 106 Longevity Intervention and Cardiomyocyte Apoptosis......Page 107 Conclusions......Page 108 References......Page 109 Introduction......Page 127 Fat Tissue Function......Page 128 Ectopic Fat Accumulation......Page 130 Inflammation......Page 131 Fat cell function and turnover......Page 133 Preadipocytes......Page 136 Acknowledgments......Page 138 References......Page 139 Embryonic Stem Cells and Induced Pluripotent Stem Cells......Page 148 Adult, or “Tissue-Specific,” Stem Cells......Page 150 Aging......Page 151 Cellular Aging......Page 152 Stem Cells and Aging......Page 153 Aging of Muscle Stem Cells......Page 154 Aging of Hematopoietic Stem Cells......Page 156 Aging of Intestinal Epithelial Stem Cells (ISCs)......Page 159 Aging of Neural Stem Cells (NSCs)......Page 161 References......Page 163 Introduction......Page 169 Human aging and longevity, life span, and life expectancy......Page 170 Telomere shortening, replication, and evolution......Page 171 Why do humans have relatively short telomeres?......Page 172 Telomere dynamics in human leukocytes......Page 173 Leukocyte telomere length dynamics: the gender and race effects......Page 174 Leukocyte telomere length and atherosclerosis......Page 175 Ramifications......Page 176 References......Page 177 Introduction......Page 183 Vitamin E......Page 184 Vitamin C......Page 188 Mixed Antioxidant Supplementation......Page 189 Lipoic Acid......Page 190 Tetrahydrocurcumin......Page 191 Cu,Zn-SOD......Page 192 Mn-SOD......Page 193 Catalase......Page 194 The effect of antioxidant enzyme reduction on mouse life span......Page 195 Cu,Zn-SOD......Page 196 Phospholipid Glutathione Peroxidase 4......Page 197 Methionine Sulfoxide Reductase......Page 198 Facts and artifacts of oxidative damage markers and their relation to the free radical theory of aging......Page 199 Synopsis, conclusions, and perspectives......Page 201 References......Page 202 Target of rapamycin (Tor) couples nutrients to growth......Page 209 Tor: A hub protein that relays signals from nutrients, growth factors, and various stresses......Page 210 Links between nutrients, tor, and life-span in D. melanogaster......Page 211 Links between nutrients, tor, and life-span in S. cerevisiae......Page 212 Links between nutrients, tor, and life-span in C. elegans......Page 213 Conclusions and outlook......Page 215 References......Page 216 Introduction......Page 221 Yeast Replicative Aging......Page 222 C. elegans......Page 226 Conserved longevity interventions......Page 227 Genetic Manipulation of Insulin/IGF-1-like Signaling......Page 228 Overexpression of Sirtuins......Page 230 Demonstration of Conservation between Yeast and Worms......Page 232 TOR Signaling Accounts for Many Conserved Longevity Factors......Page 233 IIS: A Partial Interaction with DR with Respect to Secondary Aging Phenotypes......Page 234 Sirtuins: A Complex and Unresolved Connection to DR......Page 235 TOR Signaling: A Conserved Mediator of Life-Span Extension by DR......Page 236 References......Page 237 Introduction......Page 248 Discovery of sirtuins......Page 249 Sirtuin enzymology......Page 250 Sirtuins and calorie restriction......Page 251 Mammals......Page 252 NAD+, NADH, and Nicotinamide......Page 253 Chemical inhibitors and activators of sirtuins......Page 255 SIRT1 and Energy Metabolism......Page 256 SIRT3 and Energy Metabolism......Page 258 SIRT4 and Energy Metabolism......Page 259 SIRT1 as a Tumor Suppressor......Page 260 Sirtuins and the aging cardiovascular system......Page 263 Sirtuins in inflammation and immunity......Page 265 Sirtuins in the aging brain......Page 266 Perspective......Page 267 References......Page 268 Overview of inflammatory responses......Page 280 Systemic manifestation of inflammation and aging......Page 283 Tissue inflammatory changes during aging......Page 285 Inflammation in atherosclerosis and alzheimer disease......Page 286 Cancer......Page 287 Blood glucose elevations in inflammatory processes of human aging......Page 288 Diet, metabolism, and exercise......Page 289 Genetics......Page 290 Environmental influences: an ecological perspective......Page 291 References......Page 292 Protein Homeostasis and Aging......Page 0 Introduction: proteome maintenance......Page 302 Protein homeostasis......Page 303 Molecular chaperones in quality control......Page 304 Cytosolic Chaperones in Folding and Refolding......Page 305 Chaperones in the Organelle Response to Stress......Page 306 The Catalytic Machinery......Page 307 Types of Autophagy......Page 310 Autophagy in the Removal of Soluble Proteins......Page 311 Autophagy in Aging and Longevity......Page 312 Concluding remarks and pending questions......Page 314 References......Page 316 Aging and body weight......Page 323 Frailty......Page 324 Unintentional terminal weight loss......Page 325 Decreased food intake and terminal weight loss......Page 327 Factors other than decreased food intake in terminal weight loss......Page 328 What is known and what needs to be done......Page 329 References......Page 330 Introduction......Page 334 Myelin in the context of human brain development and degeneration......Page 335 The “myelin model”: implications for human brain function and dysfunction......Page 339 References......Page 342 Introduction......Page 348 Neurovascular coupling......Page 350 Brain structural changes may result from chronic cerebral hypoperfusion......Page 352 Clinical implications of cerebral microvascular disease in aging......Page 353 Impaired Gait and Falls are Associated with Structural Changes in the Brain......Page 354 Higher Reserve may Attenuate the Impact of Cerebral Microvascular Disease on Gait and Falls......Page 356 Alzheimer Disease is More Than Plaques and Tangles......Page 357 Brain Blood Flow, Structural Changes, and Cognition......Page 358 Activating HIF-1 with desferrioxamine......Page 359 Flavonoids and Vascular Health......Page 360 Inhibitors of The Renin–Angiotensin System......Page 361 Conclusions......Page 362 References......Page 363 Aging, insulin secretion, and diabetes......Page 373 Regulation of pancreatic cells and insulin secretion......Page 375 Pancreatic cell function and aging—rodent models......Page 376 Pancreatic cell function and aging—human studies......Page 378 Relationship to insulin signaling and longevity......Page 380 Conceptual model......Page 381 References......Page 382 Introduction......Page 385 Gender Differences with Aging in Physiological Processes and Disease......Page 386 Sexual Dimorphism from X-linked/Y-linked Genes......Page 387 Species-specific Differences During Aging......Page 388 Limitation of Aging Studies in Humans and in Rodent Models......Page 389 In Terms of Reproductive Physiology and Endocrinology......Page 390 Cardiovascular Disease and Diabetes......Page 391 Cardiomyopathy of Aging......Page 392 Adrenergic Desensitization......Page 394 Increased Vascular Stiffness with Aging......Page 395 Cardiomyopathy of Aging......Page 396 Vascular Stiffness......Page 397 References......Page 398 Vascular remodeling......Page 405 Blood–brain barrier......Page 406 Cerebral blood flow......Page 407 Endothelium-dependent responses......Page 408 Oxidative stress......Page 410 Vascular inflammation......Page 412 Renin–angiotensin system......Page 413 References......Page 414 Introduction......Page 420 Cross-sectional versus Longitudinal Experimental Designs......Page 422 Sampling Considerations......Page 423 Chemoreceptor Function......Page 424 Morphological Considerations......Page 425 Changes in Collagen and Elastin Composition......Page 426 Elastic Recoil of Lung Tissue and the Chest Wall......Page 428 Static Work of Breathing......Page 430 Airway Resistance, Dynamic Airway Collapse, and the Closing Volume......Page 431 Respiratory Muscle Function......Page 432 Static Lung Volumes and Capacities......Page 433 Dynamic Lung Volumes and Ventilatory Flows......Page 434 Alveolar Ventilation and Perfusion......Page 435 Arterial Oxygen Partial Pressure......Page 437 Concluding remarks......Page 438 References......Page 439 Introduction......Page 446 Nonhuman Primate CR Studies......Page 447 The NIA Study of CR in Rhesus Monkeys......Page 448 The University of Wisconsin Study of CR in Rhesus Monkeys......Page 449 Calorie Restriction in Okinawa......Page 451 Washington University CALERIE Phase 1 Study......Page 454 Tufts University CALERIE Phase 1 Study......Page 455 Conclusions......Page 456 References......Page 457 Introduction......Page 461 Anatomy and Physiology of Skin Thermoreception......Page 462 Anatomy and Physiology of CNS Thermoreception......Page 463 Thermogenesis, heat gain, and heat retention......Page 464 Baseline Physical Activity and Posture......Page 466 Behavioral Measures for Heat Gain and Retention......Page 467 Heat loss and reduction of heat gain......Page 468 Peripheral Blood Flow......Page 469 Thermoregulatory Control......Page 470 Conclusion......Page 471 References......Page 472 Introduction......Page 477 The robustness of the sex difference in survival......Page 478 Do women age more slowly than men?......Page 480 The mortality–morbidity paradox......Page 482 The Extrinsic Hazards (Williams) Hypothesis......Page 483 The Heterogametic Sex Hypothesis......Page 485 Sex Differences in Longevity in Laboratory Rodents......Page 486 Oxidative Stress......Page 487 Size Difference......Page 489 References......Page 490 Author Index......Page 494 Subject Index......Page 556

The Handbook of the Biology of Aging, 7e, is 100% revised from the 6th edition. Providing a comprehensive synthesis and review of the latest research findings in the biology of aging, it is intended as a summary for researchers, and is also suitable as a high level textbook for graduate and upper level undergraduate courses. The 7th edition is organized into two main sections, first covering the basic aging processes and then the medical physiology of aging. This puts less emphasis on research germane only to specific species and more emphasis on the mechanisms that affect aging across species, and what this means medically for the aging of humans. This volume allows basic researchers to keep abreast of basic research outside their subdiscipline as well as recent clinical findings, while allowing medical, behavioral, and social gerontologists to understand what basic scientists and clinicians are discovering.

Coverage of basic aging processes includes the effects of dietary restriction, somatotropic axis, free radicals, apoptosis, adipose tissue, stem cells, leukocyte telomere dynamics, genetics, sirtuins, inflammation, and protein homeostasis on aging. Coverage of the medical physiology of aging includes several chapters on aging effects on the human brain including changes in brain myelination, cerebral microvasculature, and cerebral vascular dysfunction. Additional chapters include research on aging pulmonary function, insulin secretion, thermoreception and thermoregulation, calorie restriction, frailty & mortality, and sex differences in longevity and aging. This more clinically-oriented section advances our understanding of what to expect, how to prevent, and how to treat common medical effects of aging.

The Handbook of the Biology of Aging, 7e is part of the Handbooks of Aging series, including Handbook of the Psychology of Aging and Handbook of Aging and the Social Sciences, also in their 7th editions.

• Contains basic aging processes as determined by animal research as well as medical physiology of aging as known in humans
• Covers hot areas of research, like stem cells, integrated with longstanding areas of interest in aging like telomeres, mitochondrial function, etc.
• Edited by one of the fathers of gerontology (Masoro) and contributors represent top scholars in gerintology

The Handbook of the biology of aging, Seventh Edition, provides a comprehensive overview of the latest research findings in the biology of aging. Intended as a summary for researchers, it may also be used as a high level textbook for graduate courses. Contains basic aging processes as determined by animal research as well as medical physiology of aging as known in humans Covers hot areas of research, like stem cells, integrated with longstanding areas of interest in aging like telomeres, mitochondrial function, etc