Handbook of the biology of aging

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 \rvarious 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