دانلود کتاب Aging: From Fundamental Biology to Societal Impact

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Front Cover Aging Copyright Page Contents List of contributors Foreword Preface 1 The societal burden of aging 1 Global aging and health determinants in a changing world 1.1 Introduction 1.2 The geographies of a global trend 1.2.1 Global patterns and projections 1.2.2 Multiscale intraregional variations of the aging process 1.3 Environmental health in later life 1.3.1 From successful aging to the role of place and inequities 1.3.2 How environment affects physical health in old age 1.3.3 The subjective experience of place: place attachment and residential normalcy 1.4 Global stressors in a changing world 1.4.1 Welfare state and neoliberalism 1.4.2 Climate change and health in old age 1.4.3 Migrations and health in old age 1.4.4 Discrimination as a health issue for older persons 1.5 Conclusion Acknowledgments References 2 Flagship initiatives for healthy living and active aging in Europe: the European Innovation Partnership on Active and Hea... 2.1 Demographic changes and aging 2.2 The European Innovation Partnership on Active and Healthy Ageing 2.2.1 European Innovation Partnership on Active and Healthy Ageing cross-cutting initiatives 2.3 Reference sites—case studies 2.3.1 Ageing@Coimbra Reference Site 2.3.2 The Healthy Ageing Network Northern Netherlands 2.3.3 Valencia region Reference Site 2.3.4 Andalusia Reference Site 2.3.5 The Lodz4Generations Reference Site 2.3.6 Campania Reference Site (ProMIS network) 2.3.7 MACVIA-France Reference Site 2.4 Reference Site Collaborative Network 2.5 Transition from Horizon 2020 to Horizon Europe—the role of IN-4-Active and Healthy Ageing 2.6 Future perspectives Acknowledgment References 3 Aging in Africa, challenges and opportunities—the particular case of Cabo Verde 3.1 Aging in Africa and West African Region 3.2 Geography and climate of Cabo Verde 3.3 Cabo Verde, the historical healthy islands 3.4 Epidemiology of slave society 3.5 Cabo Verde Famines 3.6 Cabo Verdean population genetics 3.7 Age pyramid of Cabo Verdean population 3.8 Urbanization of Cabo Verdean population 3.9 Aging and the emergence of a new demographic model 3.10 Elderly in Cabo Verde 3.11 Health and national health service—philosophy, structures, and budget 3.12 Healthy and active aging policies 3.13 Aging and poverty 3.14 Aging and gender 3.15 To a healthy living and active aging in Cabo Verde—the future References 4 Flagship initiatives to prevent and treat diabetes as a burden of western societies 4.1 Introduction 4.1.1 Demographics of diabetes and prediabetes 4.1.2 Healthcare literacy and numeracy 4.1.3 Food insecurity and dietary quality 4.1.4 Community engagement 4.2 Impact of research: prediabetes 4.2.1 The diabetes prevention program study 4.2.2 The finnish diabetes prevention study 4.3 Lifestyle interventions 4.3.1 The national diabetes prevention program 4.3.2 Exercise 4.3.3 Pharmacologic therapy in prediabetes 4.4 Impact of research: diabetes 4.4.1 Diabetes self-management education 4.5 Summary and conclusions References 5 Determining factors on active aging in Asia and Oceania: a systematic review 5.1 Introduction 5.2 Methodology 5.2.1 Population aging in Asia and Oceania 5.2.2 Data sources and search strategies 5.2.3 Study selection 5.2.4 Bias assessment 5.2.5 Data extraction 5.3 Results 5.3.1 Exergaming/active video games 5.3.2 Health wearables and activity trackers 5.3.3 Smartphones 5.3.4 Web-based programs 5.4 Discussion and concluding remarks References 6 Healthy living and active aging in Latin America and the Caribbean countries: biological, demographic, and epidemiologica... 6.1 Introduction 6.2 Demographic and epidemiological changes in the Latin America and the Caribbean countries 6.3 Age-related biological changes and diseases in the context of Latin America and the Caribbean countries 6.3.1 Immunosenescence and infectious diseases 6.3.2 Age-related intestinal microbiota changes: the role in neurodegenerative and metabolic diseases 6.3.3 Common age-related diseases: cancer, vascular diseases, diabetes and neurodegenerative disorders 6.3.3.1 Cancer 6.3.3.2 Cardiovascular diseases 6.3.3.3 Diabetes mellitus 6.3.3.4 Neurodegenerative disorders 6.4 Health and social initiatives for the promotion of healthy living and active aging 6.4.1 Age-friendly initiatives 6.4.2 Labor force participation and active aging 6.5 Selected health issues among older people: evidence from long-term cohorts in Latin America 6.6 Conclusion References 2 The biology of aging 7 Identification of metrics of molecular and cellular resilience in humans and animal models 7.1 Biomedicine is focused on disease, not health 7.2 Comorbidities are the prevailing characteristic of older age 7.3 Chronological versus physiological age 7.4 Linking aging to disease: geroscience principles 7.5 A common thread: improvement of resilience 7.6 Defining resilience at the molecular level 7.7 Measuring molecular resilience 7.8 We need to develop resilience metrics in animal models 7.9 Translation of resilience measurements to humans 7.10 Conclusions References 8 A metabolic and mitochondrial angle on aging Abbreviations 8.1 Aging and longevity: revisiting the evolutionary perspectives and controversies 8.2 Aging and longevity: challenging the traditional views for mitochondrial-derived oxidative stress 8.3 Changes of mitochondrial function and structure associated with aging 8.3.1 Oxidative phosphorylation and aging 8.3.2 Mitochondrial morphology and dynamics in aging 8.4 A metabolic angle on aging 8.4.1 Carbohydrate metabolism and aging 8.4.2 Lipid metabolism and aging 8.4.3 Protein metabolism and aging 8.4.4 Nutrient metabolism and caloric restriction 8.5 Oxidative stress and aging 8.5.1 Reactive oxygen species and their reactions 8.5.2 Reactive oxygen species as the cause of aging 8.5.3 Antioxidant defense in aging 8.5.4 Mitochondrial free radical theory of aging 8.5.5 Accumulation of reactive oxygen species-induced damage with aging 8.5.6 Age-related oxidative modifications of mitochondria 8.6 Potential strategies against aging to increase longevity 8.6.1 Metabolic control-related approaches 8.6.1.1 Caloric/dietary restriction 8.6.1.2 Melatonin 8.6.1.3 Sirtuins activators 8.6.1.3.1 Resveratrol showed cytotoxicity against several cancers (namely leukemia, skin and prostate cancer) 8.6.1.3.2 Food nutrients 8.6.1.3.3 Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a diarylheptanoid derived from the rhizom... 8.6.1.4 Sirtuin inhibitors 8.6.1.5 Mitochondrial uncoupling 8.6.1.5.1 UCP1 was first identified in the 1970s and is the most well-known member of UCPs 8.6.1.5.2 UCP2, UCP3 and UCP4 8.6.1.5.3 2,4-dinitrophenol (DNP) and carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) are well-studied pharmac... 8.6.1.6 Physical activity 8.6.2 Mitochondria-related antioxidant approaches 8.6.2.1 What can we learn from the “eternal youth” of the naked mole rat? 8.6.2.2 Mitochondria-targeted antioxidants in delayed aging 8.6.2.2.1 MitoQ 8.6.2.2.2 SkQ1 8.6.2.2.3 AntiOxBEN2 and AntiOxCIN4 8.6.2.2.4 Other mitochondrially-targeted antioxidants 8.6.2.2.4.1 TEMPO and Mito-TEMPO 8.6.2.2.4.2 Szeto-Schiller (SS) peptides 8.7 Conclusions Acknowledgments References 9 Intercellular communication and aging 9.1 Importance of intercellular communication 9.2 The defining features of senescence 9.3 The mechanisms responsible for the induction of cellular senescence 9.4 Senescence associated secretory phenotype 9.5 Intercellular communication mediated by gap junctions and connexin channels 9.6 Intercellular communication mediated by tunneling nanotubes 9.7 Intercellular communication mediated by extracellular vesicles 9.8 Concluding remarks Acknowledgments References 10 Genomic instability and aging 10.1 Introduction 10.2 DNA strand breakage-induced genomic instability 10.3 Replication-induced genomic instability 10.3.1 Replication stress 10.3.2 Translesion DNA synthesis 10.3.3 Mismatch repair 10.4 Transcription-induced genomic instability 10.4.1 Transcription-coupled repair 10.4.2 Transcription-replication conflicts 10.5 Nucleotide pools 10.6 Mitochondrial functions in genomic integrity 10.6.1 Mitochondrial oxidative stress 10.6.2 FOXO in oxidative DNA damage response 10.6.3 Mitochondrial genome maintenance 10.6.4 Mitochondrial dysfunction 10.6.5 Mitophagy 10.7 Genomic instability in health and disease 10.7.1 Longevity 10.7.2 Progeroid syndromes 10.7.3 Cancer 10.7.4 Neurodegeneration 10.8 Aging interventions activating DNA repair 10.8.1 Exercise 10.8.2 Dietary restriction 10.8.3 Nicotinamide adenine dinucleotide 10.9 Conclusion and future perspectives Acknowledgments References 11 Telomeres and cell homeostasis in aging 11.1 What is cellular senescence 11.2 Link between cell senescence and telomeres 11.3 Critically short telomeres activate a DNA damage response and senescence 11.4 Telomere dysfunction can occur in a length-independent manner 11.5 Mechanisms by which stress accelerates telomere dysfunction 11.6 Telomere-associated DNA damage response foci accumulate during aging and disease References 12 Cellular senescence during aging 12.1 Cell senescence is a complex stress response 12.2 The building blocks of the senescent phenotype 12.2.1 Telomeres and the DNA damage response 12.2.2 Senescence-associated secretory phenotype 12.2.3 Senescence-associated mitochondrial dysfunction 12.2.4 Nutrient signaling 12.2.5 Autophagy/mitophagy 12.2.6 Epigenetic reprogramming 12.3 Senescence during aging in vivo 12.3.1 Senescence in postmitotic cells 12.3.2 Senescent cell bystander effects 12.4 Senolytics and senostatics as anti-aging interventions 12.4.1 Senolytics 12.4.2 Senostatics 12.5 Conclusion References 13 The epigenetics of aging 13.1 Introduction 13.2 Epigenetic alterations and aging 13.2.1 Histone depletion 13.2.2 Non-canonical histone variants 13.2.3 Histone acetylation 13.2.4 Histone methylation 13.2.5 ATP-dependent chromatin remodeling 13.2.6 DNA methylation 13.2.7 Non-coding RNA molecules 13.3 Epigenetic alterations and age-related diseases 13.3.1 Cancer and epigenetics 13.3.2 Neuronal diseases and epigenetics 13.3.3 Cardiovascular disease and epigenetics 13.4 Conclusions Acknowledgment Conflict of interest References 14 Disrupted cellular quality control mechanisms in aging 14.1 Aging: is it a programmed fate and/or an error accumulation? 14.2 Autophagy: an evolutionarily conserved process 14.3 Role of autophagy in aging: what can go wrong? 14.4 The chase for “eternal youth”: can autophagy-directed interventions be the much-desired youth elixir? 14.5 Going down the rabbit hole: how lysosomes modulate longevity pathways 14.6 Partners in crime: mitochondria and lysosomes need each other References 15 Stem cells, fitness, and aging 15.1 Introduction 15.2 Cell fitness and cell competition 15.3 Senescent mesenchymal stem cell phenotype 15.4 The functionality changes in senescent mesenchymal stem cells 15.5 The role of factors associated with aging 15.5.1 Oxidative stress 15.6 Genetic and epigenetic aspects 15.7 Senescence-associated secretory phenotype and the microenvironment 15.8 Therapeutic strategies to rejuvenate and increase fitness 15.9 Conclusion Acknowledgments References 16 Programming of early aging 16.1 Epidemiology of early life environment and adult aging—developmental origins of health, disease, and aging? 16.2 Early life nutrition and programming of adult aging and lifespan 16.2.1 Prenatal malnutrition, longevity, and aging 16.2.2 Can lactation and early life nutrition contribute to early aging? 16.3 Mechanisms underlying early programming of aging 16.3.1 Metabolic programming 16.3.2 Early cellular miscommunication and cellular senescence 16.3.3 Programming of genomic aging and epigenetic alterations 16.4 Early programming of aging-related diseases 16.4.1 Inflammaging 16.4.2 Cognitive decline and dementia 16.4.3 Aging-related neoplasia 16.4.4 Cardiovascular aging 16.4.5 Physical frailty 16.5 Transgenerational passage of the aging clock—reproductive cell plasticity and selection 16.6 Life interventions to “Re-set the Clock” 16.6.1 Nutrigenomics as a strategy to revert early life programming 16.6.2 Running against aging—exercise as anti-aging “medicine” 16.7 Conclusion References 3 Aging-related physiology, disease and prevention of aging-related diseases 17 Polypharmacy and medication adherence 17.1 Adherence to therapy and medication management 17.1.1 Definition and classification 17.1.2 Assessment methodologies 17.1.3 Interventions in medication nonadherence 17.1.3.1 Patient education 17.1.3.2 Supporting materials 17.1.3.3 Medication regimen optimization 17.1.3.4 Medication organizing systems 17.1.3.5 New technologies 17.2 Concept of polypharmacy 17.2.1 Potentially inappropriate medication in the elderly 17.2.2 Pharmacokinetic and pharmacodynamic changes in older people 17.3 Inappropriate polypharmacy management 17.3.1 Implicit tools 17.3.2 Explicit tools 17.3.2.1 Indicators for preventable drug-related morbidity 17.3.2.2 Beers criteria 17.3.2.3 STOPP/START criteria 17.3.2.4 EU(7)-PIM list 17.3.2.5 EURO-FORTA list 17.3.2.6 Selecting an explicit tool 17.4 Epilogue References 18 How molecular imaging studies can disentangle disease mechanisms in age-related neurodegenerative disorders 18.1 Introduction 18.2 Molecular imaging of neuroinflammation 18.3 Molecular imaging of mitochondria dysfunction and oxidative stress 18.4 Molecular imaging of misfolded proteins 18.4.1 Molecular tracers of amyloid and tau in vivo PET imaging 18.5 In vivo imaging of brain metabolic processes and activity 18.5.1 Molecular imaging of cerebral hypometabolism 18.5.2 Molecular imaging of brain functional connectivity 18.6 Imaging of iron accumulation 18.7 Emerging mechanisms of neurodegeneration 18.7.1 Glymphatic system 18.7.2 O-GLcNAc 18.8 Translational use of molecular imaging in neurodegenerative diseases 18.9 Conclusions References 19 Physical frailty Abbreviations 19.1 The concept of frailty 19.1.1 Frailty as a biological syndrome 19.1.2 Frailty as cumulative deficits 19.2 Frailty assessment 19.2.1 Frailty measurement tools 19.2.1.1 The performed frailty tools 19.2.1.2 The self-reported tools 19.2.2 A two-step frailty measurement 19.3 The biology of frailty 19.3.1 Chronic inflammation 19.3.2 Hypothalamic-pituitary axis stress response dysfunction 19.3.3 Endocrine dysregulation (dysfunctional hormone regulation) 19.3.4 Metabolic imbalance 19.3.5 Oxidative stress and mitochondrial dysfunction 19.3.6 Genomic factors 19.3.7 Metabolomic markers 19.4 Animal models of frailty 19.5 Interventions to attenuate frailty 19.5.1 Pharmacological interventions 19.5.2 Nonpharmacological interventions 19.6 Conclusion References 20 The extracellular matrix in cardiovascular aging Abbreviations 20.1 Introduction 20.2 Physiological alterations of the aged heart 20.2.1 Aging induces functional and morphologic cardiac alterations 20.3 Young cardiac extracellular matrix 20.3.1 Collagens 20.3.2 Elastin 20.3.3 Matricellular proteins: secreted protein, acidic and rich in cysteine and thrombospondin 20.3.4 Glycosaminoglycans and proteoglycans 20.3.5 Adhesive proteins: fibronectin and laminin 20.3.6 Basement membrane 20.4 Aged cardiac extracellular matrix 20.4.1 Collagen matrix—synthesis, deposition and modification with age 20.4.1.1 Age-related alterations in myocardial collagen content 20.4.1.2 Age-related alterations in myocardial collagen types 20.4.1.3 Age-related alterations in myocardial collagen cross-linking 20.4.2 Alterations on glycosaminoglycans and proteoglycans in the aged heart 20.4.3 Alterations on matrix adhesive proteins with aging 20.5 How does the aged heart respond to disease? 20.5.1 Age-associated extracellular matrix remodeling in MI 20.5.2 Age-associated cardiac extracellular matrix remodeling in heart failure 20.6 Conclusions and perspectives Acknowledgments References 21 Aging-related neoplasia 21.1 Introduction 21.2 Aging and the risk of cancer 21.3 Cellular senescence and carcinogenesis 21.4 Oxidative stress and carcinogenesis in aging 21.5 The hallmarks of aging and neoplasia 21.5.1 Cell signaling 21.5.2 Telomeres and telomerase 21.5.3 Genomic instability 21.5.4 Epigenetic aging and neoplasia 21.5.5 Proteostasis 21.5.6 Metabolism deregulation 21.5.7 Immune system dysfunction 21.5.8 Persistent viral infection 21.5.9 Stem cells 21.6 Neoplasias and aging 21.6.1 Aging-related neoplasias 21.6.2 Cancer therapeutics and aging 21.7 Conclusion References 22 Multidimensional frailty as an outcome of biological aging: immunosenescence and inflammaging in the life course perspective 22.1 Introduction 22.2 Relevance of mechanisms of aging for medicine in the 21st century 22.3 Two facets of immunosenescence and inflammaging 22.4 Pathophysiological relevance of immunosenescence and inflammaging in the context of frailty: relevance for COVID-19 22.5 Concluding remarks and research outlook References Further reading 23 Geroscience: a unifying view on aging as a risk factor 23.1 Centenarians: a growing population 23.2 Morbidity compression in centenarians 23.3 Limits of human longevity 23.4 Exceptional aging “must-haves” 23.4.1 Low-grade inflammation 23.4.2 Genetic signature 23.4.3 Fine-tuned apoptosis 23.4.4 Stem cell pluripotency 23.4.5 Healthy lifestyle 23.5 Exceptional homeostasis in exceptional aging 23.6 Centenarians beyond 120? References 4 The future and innovation in aging 24 Aging support with socially assistive robots 24.1 Introduction 24.1.1 Social robotics tools for demanding societies 24.1.2 Where are we in social robotics? 24.2 Where is social robotics heading? 24.2.1 Social robots for aging societies 24.2.2 User behaviors under uncertainty—the bayesian user model 24.2.3 Online knowledge integration using learning 24.3 Results with a team of robots 24.4 User’s attributes from distributed, asynchronous data 24.5 Collectively cluster users into distinguishable profiles 24.6 Discussion Acknowledgments References 25 Machine learning in the context of better healthcare in aging 25.1 Introduction 25.2 Machine learning overview 25.3 A review of machine learning applications for aging research 25.4 Telemonitoring data mining for hearth failure management 25.4.1 Heart failure condition 25.4.1.1 myHeart study 25.4.2 Algorithms for heart failure management 25.4.2.1 Diagnosis of heart failure arrhythmias 25.4.2.1.1 Preprocessing 25.4.2.1.2 Feature extraction 25.4.2.1.3 Classification 25.4.2.2 Prognosis of heart failure decompensation 25.4.2.2.1 Time series clustering 25.4.2.2.2 Prediction approach 25.4.3 Experimental results 25.4.3.1 Diagnosis of heart failure arrhythmias 25.4.3.1.1 Segmentation 25.4.3.1.2 Premature ventricular contractions and atrial fibrillation episodes 25.4.3.2 Prognosis of heart failure decompensation 25.4.4 Discussion 25.5 Machine learning for the English Longitudinal Study of Ageing 25.5.1 A brief overview of random forest classifiers 25.5.2 Preparing the English Longitudinal Study of Ageing-nurse data for the classification task 25.5.2.1 Data-driven missing value replacement 25.5.2.2 Adapting the random forest algorithm to longitudinal data 25.5.3 Computational results 25.5.3.1 Predictive performance results 25.6 Feature importance analysis 25.7 Conclusion References 26 The future of integrated care in aged individuals 26.1 Introduction 26.2 The current model is more and more inadequate 26.3 The avoidable suffering 26.4 An integrated care approach 26.4.1 Healthy aging and disease prevention 26.4.2 Patient-centeredness and multimorbidity 26.4.3 Dementia 26.4.4 Palliative, end life, and bereavement care 26.5 Key messages References 27 Moving from reactive to preventive medicine 27.1 Introduction 27.2 Aging and major chronic diseases 27.3 The mechanistic interplay between aging and age-related diseases. In the search of evidence for preventive medicine 27.3.1 Immunosenescence and age-related chronic diseases 27.3.2 Epigenetic drift and age-related chronic diseases 27.4 Age-related diseases—prevention initiatives are in order 27.5 Do we have preventive strategies for ameliorating age-related diseases? 27.5.1 Non-pharmacological approaches 27.5.2 Pharmacological interventions 27.6 Cardiovascular disease: the success of prevention 27.6.1 Hypertension: the most prevalent cardiovascular risk factor 27.7 Low-density lipoproteins-cholesterol lowering: the lower, the better 27.7.1 The need to control the obesity pandemic 27.7.2 Primordial prevention: the sooner, the better 27.8 Concluding remarks References 28 Personalized medicine: will it work for decreasing age-related morbidities? 28.1 Introduction 28.2 Historical perspective 28.3 Slowing aging with GeroScience 28.3.1 The biological hallmarks of aging 28.3.2 A case for personalized aging 28.4 Personalized medicine for optimal longevity 28.5 Emerging predictors of “biological aging” 28.5.1 Epigenetic clocks 28.5.2 Transcriptomics 28.5.3 Metabolomics and proteomics 28.5.4 The gut microbiome 28.6 Applying personalized medicine to GeroScience 28.6.1 Personalized nutrition 28.7 Challenges and barriers to implementing personalized aging 28.7.1 Minimizing the risk-benefit ratio 28.7.2 Increasing diversity in clinical research 28.7.3 Improving adherence and accessibility 28.7.4 Innovation in clinical trial design 28.7.5 Ethical and policy concerns 28.7.6 Cross-disciplinary innovation 28.8 Conclusion References 29 Interventions that target fundamental aging mechanisms: myths and realities 29.1 Introduction 29.2 Pillars of aging 29.3 Genomic instability 29.3.1 Telomere attrition 29.3.2 Epigenetic alterations 29.3.3 Loss of proteostasis 29.3.4 Deregulated nutrient sensing 29.3.5 Mitochondrial dysfunction 29.3.6 Cellular senescence 29.3.7 Stem cell exhaustion 29.3.8 Altered intercellular communication 29.4 Unitary theory of fundamental aging processes 29.5 Health span versus lifespan 29.6 Myths and realities 29.6.1 Senolytics 29.6.2 Other pharmacological interventions 29.6.2.1 Metformin 29.6.2.2 Rapamycin 29.6.2.3 Resveratrol 29.6.2.4 NAD+/NMN and inhibitors of CD38 29.6.2.5 17-α-Estradiol 29.6.2.6 Ketogenic agents 29.6.3 Behavioral/dietary interventions 29.6.3.1 Caloric restriction/fasting/food clocking 29.6.3.2 Exercise 29.7 Clinical trials and treating disease 29.7.1 Safety; risk/benefit ratio 29.7.2 Combining or sequencing therapies 29.7.3 Translational geroscience network 29.8 Conclusion Conflict of interest disclosure References 30 Being a frail older person at a time of the COVID-19 pandemic 30.1 Introduction 30.1.1 A minority of community-dwelling older adults are frail 30.1.2 Frailty in the time of a pandemic: the “measured” versus the “lived” 30.2 The community perspective 30.2.1 COVID-19-related challenges in community-dwelling frail older people 30.2.2 A glimpse of hope 30.3 The hospital perspective 30.3.1 Atypical presentations 30.3.2 Biological heterogeneity of the population of hospitalized older people 30.3.3 Ethical considerations 30.3.4 Optimization of the hospital environment and opportunities for in-hospital rehabilitation 30.3.5 Hospital-associated deconditioning and post-COVID-19 fatigue 30.4 The nursing home perspective 30.5 Research on COVID-19 treatments and service development perspectives 30.6 Conclusions Competing interest Funding References 31 Aging: an illustrated adventure Index Back Cover