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

The Handbook of the Biology of Aging, 7e, is 100% revised from the 6 th 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 7 th 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 7 th 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 Cover Page......Page 1 Title Page......Page 4 ISBN 9780123786388......Page 5 Contents......Page 6 Contributors......Page 8 Foreword......Page 11 Preface......Page 13 About the Editors......Page 15 Part 1: Basic Aging Processes......Page 16 Introduction......Page 18 DR Regimens in C. elegans......Page 19 Criteria......Page 20 Energy Sensors: Insulin–PI3K, SIR2, AMPK, TOR......Page 24 Transcriptional Regulators: FoxO/daf-16, FoxA/pha-4, NFE2/skn-1, HIF-1,HSF-1, CBP-1......Page 25 Fly DR: SIR2, TOR, and FoxO......Page 27 DR in Mammals: SIR2, TOR, Insulin–FoxO, NFE2......Page 28 Type of Nutrients......Page 29 Tissue Specificity......Page 30 DR Mimetics......Page 31 References......Page 32 Introduction......Page 40 Body size and composition......Page 41 Glucose metabolism and insulin sensitivity......Page 42 Oxidative metabolism and related factors of stress resistance......Page 43 Cognitive function......Page 45 Immune function......Page 47 Age-related pathology and neoplasia......Page 49 References......Page 50 Introduction......Page 62 Complex I ROS Production......Page 63 Complex III Inhibitors......Page 65 Electron Transfer Flavoprotein–Ubiquinone Oxidoreductase (ETF–Q Oxidoreductase)......Page 66 Mitochondrial antioxidant systems......Page 67 Free radical theories of aging......Page 69 Conclusions......Page 71 References......Page 72 4 Aging and Apoptosis in Muscle......Page 78 Myonuclear Apoptosis......Page 79 Myonuclear Apoptotic Signaling in Skeletal Muscle......Page 80 Cellular Conditions for Activation of the Intrinsic Apoptotic Pathway......Page 81 Mitochondrial Bioenergetics in Aging Muscle......Page 82 Mitochondrial Permeability......Page 83 Oxidative Stress and Mitochondria......Page 84 The BCL-2 Protein Family......Page 85 Caspase-Independent Signaling......Page 86 Mitochondria-Mediated Signaling for Apoptosis in Sarcopenia......Page 87 TNF- and Death Receptor Signaling......Page 92 Cross Talk between Extrinsic and Intrinsic Apoptotic Signaling......Page 96 Cellular Conditions that Activate the SR/ER–Ca2 Stress Apoptotic Pathway......Page 97 Signaling via the SR–Ca2+ Stress Apoptotic Pathway......Page 98 The Role of MyoD in Apoptosis of MPCs......Page 99 Interventions by Muscle Loading......Page 100 Unloading and Disuse in Skeletal Muscle......Page 109 Regulation of Apoptosis by Aerobic Exercise......Page 110 Aging and cardiomyocyte apoptosis......Page 111 Apoptosis and the Aging Heart......Page 112 Modulation of Bcl-2 and Bax in the Aging Heart......Page 113 Longevity Intervention and Cardiomyocyte Apoptosis......Page 114 Conclusions......Page 115 References......Page 116 Introduction......Page 134 Fat Tissue Function......Page 135 Ectopic Fat Accumulation......Page 137 Inflammation......Page 138 Fat cell function and turnover......Page 140 Preadipocytes......Page 143 Acknowledgments......Page 145 References......Page 146 Embryonic Stem Cells and Induced Pluripotent Stem Cells......Page 156 Adult, or “Tissue-Specific,” Stem Cells......Page 158 Aging......Page 159 Cellular Aging......Page 160 Stem Cells and Aging......Page 161 Aging of Muscle Stem Cells......Page 162 Aging of Hematopoietic Stem Cells......Page 164 Aging of Intestinal Epithelial Stem Cells (ISCs)......Page 167 Aging of Neural Stem Cells (NSCs)......Page 169 References......Page 171 Introduction......Page 178 Human aging and longevity, life span, and life expectancy......Page 179 Telomere shortening, replication, and evolution......Page 180 Why do humans have relatively short telomeres?......Page 181 Telomere dynamics in human leukocytes......Page 182 Leukocyte telomere length dynamics: the gender and race effects......Page 183 Leukocyte telomere length and atherosclerosis......Page 184 Ramifications......Page 185 References......Page 186 Introduction......Page 192 Vitamin E......Page 193 Vitamin C......Page 197 Mixed Antioxidant Supplementation......Page 198 Lipoic Acid......Page 199 Tetrahydrocurcumin......Page 200 Cu,Zn-SOD......Page 201 Mn-SOD......Page 202 Catalase......Page 203 The effect of antioxidant enzyme reduction on mouse life span......Page 204 Cu,Zn-SOD......Page 205 Phospholipid Glutathione Peroxidase 4......Page 206 Methionine Sulfoxide Reductase......Page 207 Facts and artifacts of oxidative damage markers and their relation to the free radical theory of aging......Page 208 Synopsis, conclusions, and perspectives......Page 210 References......Page 211 Target of rapamycin (Tor) couples nutrients to growth......Page 218 Tor: A hub protein that relays signals from nutrients, growth factors, and various stresses......Page 219 Links between nutrients, tor, and life-span in D. melanogaster......Page 220 Links between nutrients, tor, and life-span in S. cerevisiae......Page 221 Links between nutrients, tor, and life-span in C. elegans......Page 222 Conclusions and outlook......Page 224 References......Page 225 Introduction......Page 230 Yeast Replicative Aging......Page 231 C. elegans......Page 235 Conserved longevity interventions......Page 236 Genetic Manipulation of Insulin/IGF-1-like Signaling......Page 237 Overexpression of Sirtuins......Page 239 Demonstration of Conservation between Yeast and Worms......Page 241 TOR Signaling Accounts for Many Conserved Longevity Factors......Page 242 IIS: A Partial Interaction with DR with Respect to Secondary Aging Phenotypes......Page 243 Sirtuins: A Complex and Unresolved Connection to DR......Page 244 TOR Signaling: A Conserved Mediator of Life-Span Extension by DR......Page 245 References......Page 246 Introduction......Page 258 Discovery of sirtuins......Page 259 Sirtuin enzymology......Page 260 Sirtuins and calorie restriction......Page 261 Mammals......Page 262 NAD+, NADH, and Nicotinamide......Page 263 Chemical inhibitors and activators of sirtuins......Page 265 SIRT1 and Energy Metabolism......Page 266 SIRT3 and Energy Metabolism......Page 268 SIRT4 and Energy Metabolism......Page 269 SIRT1 as a Tumor Suppressor......Page 270 Sirtuins and the aging cardiovascular system......Page 273 Sirtuins in inflammation and immunity......Page 275 Sirtuins in the aging brain......Page 276 Perspective......Page 277 References......Page 278 Overview of inflammatory responses......Page 290 Systemic manifestation of inflammation and aging......Page 293 Tissue inflammatory changes during aging......Page 295 Inflammation in atherosclerosis and alzheimer disease......Page 296 Cancer......Page 297 Blood glucose elevations in inflammatory processes of human aging......Page 298 Diet, metabolism, and exercise......Page 299 Genetics......Page 300 Environmental influences: an ecological perspective......Page 301 References......Page 302 Introduction: proteome maintenance......Page 312 Protein homeostasis......Page 313 Molecular chaperones in quality control......Page 314 Cytosolic Chaperones in Folding and Refolding......Page 315 Chaperones in the Organelle Response to Stress......Page 316 The Catalytic Machinery......Page 317 Types of Autophagy......Page 320 Autophagy in the Removal of Soluble Proteins......Page 321 Autophagy in Aging and Longevity......Page 322 Concluding remarks and pending questions......Page 324 References......Page 326 Part 2: Medical Physiology of Aging......Page 334 Aging and body weight......Page 336 Frailty......Page 337 Unintentional terminal weight loss......Page 338 Decreased food intake and terminal weight loss......Page 340 Factors other than decreased food intake in terminal weight loss......Page 341 What is known and what needs to be done......Page 342 References......Page 343 Introduction......Page 348 Myelin in the context of human brain development and degeneration......Page 349 The “myelin model”: implications for human brain function and dysfunction......Page 353 References......Page 356 Introduction......Page 362 Neurovascular coupling......Page 364 Brain structural changes may result from chronic cerebral hypoperfusion......Page 366 Clinical implications of cerebral microvascular disease in aging......Page 367 Impaired Gait and Falls are Associated with Structural Changes in the Brain......Page 368 Higher Reserve may Attenuate the Impact of Cerebral Microvascular Disease on Gait and Falls......Page 370 Alzheimer Disease is More Than Plaques and Tangles......Page 371 Brain Blood Flow, Structural Changes, and Cognition......Page 372 Activating HIF-1 with desferrioxamine......Page 373 Flavonoids and Vascular Health......Page 374 Inhibitors of The Renin–Angiotensin System......Page 375 Conclusions......Page 376 References......Page 377 Aging, insulin secretion, and diabetes......Page 388 Regulation of pancreatic cells and insulin secretion......Page 390 Pancreatic cell function and aging—rodent models......Page 391 Pancreatic cell function and aging—human studies......Page 393 Relationship to insulin signaling and longevity......Page 395 Conceptual model......Page 396 References......Page 397 Introduction......Page 400 Gender Differences with Aging in Physiological Processes and Disease......Page 401 Sexual Dimorphism from X-linked/Y-linked Genes......Page 402 Species-specific Differences During Aging......Page 403 Limitation of Aging Studies in Humans and in Rodent Models......Page 404 In Terms of Reproductive Physiology and Endocrinology......Page 405 Cardiovascular Disease and Diabetes......Page 406 Cardiomyopathy of Aging......Page 407 Adrenergic Desensitization......Page 409 Increased Vascular Stiffness with Aging......Page 410 Cardiomyopathy of Aging......Page 411 Vascular Stiffness......Page 412 References......Page 413 Vascular remodeling......Page 420 Blood–brain barrier......Page 421 Cerebral blood flow......Page 422 Endothelium-dependent responses......Page 423 Oxidative stress......Page 425 Vascular inflammation......Page 427 Renin–angiotensin system......Page 428 References......Page 429 Introduction......Page 436 Cross-sectional versus Longitudinal Experimental Designs......Page 438 Sampling Considerations......Page 439 Chemoreceptor Function......Page 440 Morphological Considerations......Page 441 Changes in Collagen and Elastin Composition......Page 442 Elastic Recoil of Lung Tissue and the Chest Wall......Page 444 Static Work of Breathing......Page 446 Airway Resistance, Dynamic Airway Collapse, and the Closing Volume......Page 447 Respiratory Muscle Function......Page 448 Static Lung Volumes and Capacities......Page 449 Dynamic Lung Volumes and Ventilatory Flows......Page 450 Alveolar Ventilation and Perfusion......Page 451 Arterial Oxygen Partial Pressure......Page 453 Concluding remarks......Page 454 References......Page 455 Introduction......Page 462 Nonhuman Primate CR Studies......Page 463 The NIA Study of CR in Rhesus Monkeys......Page 464 The University of Wisconsin Study of CR in Rhesus Monkeys......Page 465 Calorie Restriction in Okinawa......Page 467 Washington University CALERIE Phase 1 Study......Page 470 Tufts University CALERIE Phase 1 Study......Page 471 Conclusions......Page 472 References......Page 473 Introduction......Page 478 Anatomy and Physiology of Skin Thermoreception......Page 479 Anatomy and Physiology of CNS Thermoreception......Page 480 Thermogenesis, heat gain, and heat retention......Page 481 Baseline Physical Activity and Posture......Page 483 Behavioral Measures for Heat Gain and Retention......Page 484 Heat loss and reduction of heat gain......Page 485 Peripheral Blood Flow......Page 486 Thermoregulatory Control......Page 487 Conclusion......Page 488 References......Page 489 Introduction......Page 494 The robustness of the sex difference in survival......Page 495 Do women age more slowly than men?......Page 497 The mortality–morbidity paradox......Page 499 The Extrinsic Hazards (Williams) Hypothesis......Page 500 The Heterogametic Sex Hypothesis......Page 502 Sex Differences in Longevity in Laboratory Rodents......Page 503 Oxidative Stress......Page 504 Size Difference......Page 506 References......Page 507 A......Page 512 B......Page 514 C......Page 519 D......Page 523 E......Page 525 F......Page 527 G......Page 529 H......Page 532 J......Page 536 K......Page 538 L......Page 541 M......Page 545 N......Page 550 O......Page 551 P......Page 552 Q......Page 555 R......Page 556 S......Page 558 T......Page 564 U......Page 566 V......Page 567 W......Page 568 X......Page 570 Y......Page 571 Z......Page 572 B......Page 574 D......Page 575 H......Page 576 M......Page 577 P......Page 578 S......Page 579 U......Page 580 Y......Page 581 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