Title Page -- Copyright Page -- Contents -- List of contributors -- Preface -- Acknowledgment -- Part I - Ageing of cells and organisms -- Chapter 1 Human ageing, a biological view -- 1.1 Introduction -- 1.2 Human ageing and frailty -- 1.2.1 Mortality curves -- 1.2.2 Susceptibility to disease and mortality -- 1.2.3 Age-related and age-dependent diseases -- 1.3 Fundamental causes -- 1.4 Experimental approach to human ageing -- 1.4.1 Ageing models in dividing cells: Replicative senescence and telomere involvement -- 1.4.2 Stress-induced premature senescence -- 1.4.3 Ageing in organs and tissues -- 1.4.4 Lipofuscin deposition following organelle dysfunction and damage accumulation -- 1.4.5 Damage consequences: Dysfunctional organelles and cell functional decline. Cell loss -- 1.5 Involving genes in organism ageing and longevity -- 1.5.1 Longevous humans -- 1.5.2 Experimental approaches -- 1.5.2.1 The insulin/IGF-1 axis -- 1.5.2.2 IGF-1 signaling into FOXO proteins -- 1.5.2.3 Other pathways -- 1.6 Conclusions and prospects -- Acknowledgment -- References -- Chapter 2 To eat or not to eat - Anti-ageing effects of energy restriction -- Part 1 -- 2.1 Energy restriction as more than a weight-loss strategy -- 2.2 Restriction of energy vs restriction of nutrients -- 2.2.1 Experimental models of energy restriction -- 2.2.2 Observational studies and the first human trial of energy restriction: CALERIE study -- 2.3 Effects of energy restriction on organisms -- 2.3.1 Increased longevity and health of energy-restricted organisms -- 2.3.2 Body composition, temperature and resting metabolic rate -- 2.3.3 Metabolism and insulin sensitivity -- 2.3.4 Immune system and inflammatory modulation -- 2.3.5 Neuroendocrine axes and adipokines -- 2.3.6 Growth factors and cytoprotective effects -- 2.4 Cellular and molecular effects of energy restriction.

2.4.1 Modulation of gene expression -- 2.4.2 Molecular mechanisms of sirtuins -- 2.4.2.1 Sirtuin 1 -- 2.4.2.2 Sirtuin 6 -- 2.4.2.3 Sirtuin 7 -- 2.4.2.4 Sirtuin 3 -- 2.4.2.5 Sirtuins 4 and 5 -- 2.4.2.6 Sirtuin 2 -- 2.4.3 AMPK -- 2.4.4 Oxidative stress and metabolic reprogramming -- 2.4.5 Autophagy and mTOR signaling -- 2.5 Energy restriction mimetics -- 2.5.1 Sirtuin activity stimulators -- 2.5.2 Antidiabetic drugs -- 2.5.3 Rapamycine -- 2.5.4 Polyamines -- 2.5.5 Antilipolytic drugs -- Part 2 -- 2.6 Obesity and ageing -- 2.6.1 Obesity as a premature death inducer -- 2.6.2 Adipose tissue and metabolic dysregulation -- 2.6.2.1 Adipose tissue and disruption of endocrine secretion of adipokines -- 2.6.3 Mitochondrial dysfunction -- 2.6.4 Endoplasmic reticulum stress -- 2.6.4.1 Endoplasmic reticulum stress-induced unfolded protein response -- 2.6.4.2 Ageing-induced modification in unfolded protein response -- 2.6.4.3 Obesity-induced endoplasmic reticulum stress -- 2.6.5 Anti-obesity effects of natural compounds extracted from plants -- 2.6.5.1 Polyphenols -- 2.6.5.1.1 Cathechins -- 2.6.5.1.2 Curcumin -- 2.6.5.1.3 Resveratrol -- 2.6.5.1.4 Quercetin -- 2.6.5.1.5 Isoflavones -- 2.6.6 Anti-obesity effects of minerals (magnesium) -- 2.7 Conclusion -- Acknowledgment -- References -- Chapter 3 Nutrition, epigenetics and ageing -- 3.1 Introduction -- 3.2 Epigenetics -- 3.2.1 DNA methylation -- 3.2.2 Histone modifications -- 3.2.3 Noncoding RNAs -- 3.2.4 The function of epigenetic mechanisms -- 3.3 Epigenetics and ageing -- 3.3.1 DNA methylation profiles and ageing -- 3.3.2 Histone modifications and ageing -- 3.3.3 MicroRNAs and ageing -- 3.4 Influence of nutrition on epigenetic modifications -- 3.4.1 Nutritional modulation of epigenetic enzyme activity -- 3.4.2 Influence of nutrition on substrate availability for epigenetic modifications.

3.4.3 Critical windows and the developmental origins hypothesis -- 3.5 Nutrition, epigenetics and ageing -- 3.5.1 Overview -- 3.5.2 Specific dietary regimens and nutrients that influence epigenetics and ageing -- 3.5.2.1 Dietary restriction -- 3.5.2.2 Dietary polyphenols -- 3.5.2.3 One-Carbon metabolism -- 3.6 Conclusions and future perspective -- References -- Part II - Nutritional modulation of age-related organ functional decline -- Chapter 4 Nutritional interventions in age-related genetic and epigenetic instability and cancer -- 4.1 Cancer as an age-associated disease -- 4.2 Genetic and epigenetic alterations as molecular mechanisms underlying carcinogenesis -- 4.3 Diet, nutrition and cancer -- 4.4 Targeting age-related genomic and epigenomic alterations with nutritional interventions for cancer prevention -- 4.4.1 Folate -- 4.4.2 Energy restriction -- 4.4.3 Bioactive food components -- 4.5 Conclusions and perspectives -- Acknowledgment -- References -- Chapter 5 Nutraceuticals in immunosenescence -- 5.1 Introduction -- 5.2 The immune response in ageing -- 5.2.1 Phagocytes -- 5.2.2 Natural killer cells -- 5.2.3 T cells -- 5.2.4 B cells -- 5.3 Micronutrients that modulate immunosenescence -- 5.3.1 Zinc -- 5.3.2 Copper -- 5.3.3 Iron -- 5.3.4 Selenium -- 5.4 Probiotics and prebiotics -- 5.4.1 Probiotics -- 5.4.2 Prebiotics -- 5.5 Dietary lipids -- 5.6 Polyphenols -- 5.7 Conclusion and future directions -- Acknowledgments -- References -- Chapter 6 Cardiovascular ageing -- 6.1 Age-related cardiac changes -- 6.1.1 Heart changes -- 6.1.1.1 Structural changes -- 6.1.1.1.1 Changes in heart valves -- 6.1.1.2 Functional changes -- 6.1.1.2.1 Cardiac systolic function -- 6.1.1.2.2 Cardiac diastolic function -- 6.1.1.2.3 Changes in cardiac conduction system and in heart rate -- 6.1.1.2.4 Cardiac adrenergic responsiveness.

6.1.1.3 Changes in cardioprotective and repair processes -- 6.2 Age-related vascular changes -- 6.2.1 Central arterial changes -- 6.2.1.1 Arterial structural changes -- 6.2.1.1.1 Luminal dilatation -- 6.2.1.1.2 Arterial stiffening and thickening -- 6.2.1.1.3 Vascular calcification -- 6.2.1.1.4 Dimensional variation -- 6.2.2 Peripheral arterial changes -- 6.2.3 Arterial functional changes -- 6.2.3.1 Blood pressure -- 6.3 Changes in the interaction between heart and arterial system -- 6.4 Endothelial dysfunction -- 6.5 Erectile dysfunction as an early signal of cardiovascular disease -- 6.5.1 The erection mechanism -- 6.5.2 Contribution of ageing to erectile dysfunction onset -- 6.5.2.1 Age-related structural and molecular modifications of erectile tissue -- 6.6 Diet, nutrition and cardiovascular ageing -- 6.6.1 Obesity, energy restriction and cardiovascular ageing -- 6.6.2 Diet patterns and cardiovascular ageing -- 6.6.2.1 Contribution of dietary pattern to erectile dysfunction onset -- 6.7 Nutritional intervention for cardiovascular disease prevention or amelioration -- 6.7.1 Nutritional pattern modulation -- 6.7.2 Intervention of specific nutrients in cardiovascular disease protection -- 6.7.2.1 Polyphenolic compounds -- 6.7.2.2 l-Carnitine and l-arginine -- 6.7.2.3 Fatty acids -- 6.7.2.4 Vitamins -- 6.7.2.5 Minerals -- 6.7.2.6 Caffeine -- 6.8 Conclusions -- References -- Chapter 7 Bone and muscle ageing -- 7.1 Introduction -- 7.1.1 Determinants of bone loss in ageing -- 7.1.2 Regulation of muscle atrophy in ageing -- 7.2 Osteoporosis and fragility fractures in the elderly -- 7.3 Nutritional mechanisms of age-related bone loss -- 7.4 Calcium and vitamin D and the ageing skeleton: Efficacy in the treatment of osteoporosis -- 7.5 Skeletal muscle age-related contributory mechanisms.

7.6 The role of nutrition in preventing ageing skeletal muscle atrophy -- 7.6.1 Protein -- 7.6.2 PUFA and inflammation -- 7.6.3 Anti-oxidants and oxidative stress -- 7.6.4 Vitamin D -- 7.6.5 Food and dietary patterns -- 7.7 Resistance exercise and nutrition: Effective treatment strategy to counteract age-related muscle wasting and bone loss -- 7.7.1 Protein and resistance exercise -- 7.8 Concluding remarks -- References -- Chapter 8 Nutrition and the ageing eye -- 8.1 The ageing eye -- 8.1.1 The lens -- 8.1.2 The retina -- 8.2 Nutrients in the structure and physiology of the healthy human eye -- 8.2.1 Vitamins -- 8.2.2 Polyunsaturated fatty acids -- 8.2.3 Zinc -- 8.3 The human eye and the oxidative stress -- 8.4 The anti-oxidant systems in the eye -- 8.5 How can diet interfere with the ocular anti-oxidant system? -- 8.6 Nutritional intervention in age-associated eye diseases -- 8.6.1 Cataract -- 8.6.1.1 The blue mountains eye study -- 8.6.1.2 The beaver dam eye study -- 8.6.1.3 The India age-related eye disease study -- 8.6.1.4 The Spanish segment of European eye study (EUREYE) -- 8.6.1.5 The physicians' health study -- 8.6.1.6 The women's health study -- 8.6.1.7 The age-related eye disease study (AREDS) -- 8.6.1.8 The age-related eye disease study 2 (AREDS2) -- 8.6.2 Age-related macular degeneration -- 8.6.2.1 AREDS -- 8.6.2.2 AREDS2 -- 8.7 Nutrigenomics -- 8.8 Conclusions -- References -- Chapter 9 Beauty from the inside: Nutrition and skin ageing -- 9.1 Introduction -- 9.2 Vitamins -- 9.2.1 Vitamin C (l-ascorbic acid) -- 9.2.2 Vitamin E (tocopherol) -- 9.2.3 Vitamin B6 -- 9.2.4 Carotenoids -- 9.2.5 Vitamin D -- 9.3 Polyphenols and flavonoids -- 9.4 Polyunsaturated fatty acids -- 9.5 Pre- and probiotics -- 9.6 Conclusions -- References -- Chapter 10 Retarding brain ageing and cognitive decline -- 10.1 Ageing and brain.

10.2 From "healthy ageing" to dementia.