Cover -- Half-title -- Title -- Copyright -- Contents -- List of contributors -- Preface -- PART I Epidemiology -- 1 Epidemiology of aging -- Descriptive epidemiology -- Medical implications of aging -- Increased prevalence of chronic conditions -- Increased morbidity and mortality from acute conditions -- Goals of medical treatment -- Social implications of aging -- Conclusions -- REFERENCES -- 2 Introduxtion Epidemiology of anemia in older adults -- Introduction -- Prevalence of anemia in older adults -- Types of anemia -- Anemia with nutrient deficiency -- Anemia of chronic inflammation (chronic disease) -- Anemia of chronic kidney disease -- Unexplained anemia -- Summary -- REFERENCES -- 3 Introduxtion Cancer in the older person: a comprehensive approach -- Introduction -- Elderly patients with cancer: how much does it cost? -- Before starting any treatment -- Comprehensive geriatric assessment -- Components of comprehensive geriatric assessment -- Functional dependency -- Cognitive impairment -- Depression -- Falls and impaired mobility -- Nutritional assessment -- Pain -- Urinary incontinence -- Visual and hearing impairment -- Elder abuse -- Quality of life -- Conclusions -- REFERENCES -- 4 Introduxtion From . tness to frailty: toward a nosologic classi. cation of the older aged person -- Introduction -- Biology and physiology of aging -- Clinical assessment of aging -- Comprehensive geriatric assessment (CGA) -- Function -- Comorbidity -- Geriatric syndromes -- Social resources -- Nutrition -- Polypharmacy -- Clinical application of the CGA -- Limitation of the geriatric assessment -- Shortened forms of assessment -- Practical applications of the geriatric assessment -- Other forms of geriatric assessment -- Tests of physical performance -- Laboratory assessment -- Frailty, real and elusive -- Functional dependence and disability.

Toward a nosologic classification of aging -- REFERENCES -- PART II Hematopoiesis -- 5 Stem cell exhaustion and aging -- Do hematopoietic stem cells show age-related loss of function? -- Identification and study of the pluripotent HSC -- Systemic versus cellular aging -- Model systems of stem cell aging -- Regulation of aged HSC proliferation -- Self-renewal of HSCs is altered during aging -- Telomeres shorten with age -- Differentiation of stem cells -- Mobilization of stem cells -- HSC homing during aging -- DNA repair and genomic instability during aging -- Apoptosis -- Genetic regulation of stem cell aging -- A locus on chromosome 2 linked to aging of stem cells -- Conclusion -- REFERENCES -- 6 Introduxtion Hematopoietic microenvironment and age -- Introduction -- HM and the HSC niche -- Definition of aging -- Hematopoietic stem cells and age -- The hematopoietic microenvironment and age -- Age-related changes in humans -- Conclusions -- REFERENCES -- 7 Replicative senescence, aging, and cancer -- Introduction -- Proliferation is essential for immune function -- Replicative senescence in T cells -- Elderly persons have high proportions of senescent T cells -- What are the in-vivo consequences of senescent CD8 T cells? -- Senescent T cells and cancer -- Solutions to the problem of T-cell replicative senescence -- ACKNOWLEDGEMENTS -- REFERENCES -- 8 Qualitative changes of hematopoiesis -- Introduction -- Incidence of qualitative hematopoietic abnormalities -- Risk factors -- Genetic factors -- Environmental factors -- Immunologic factors -- Other factors -- History -- Dysplasia and hematologic characteristics -- Qualitative changes in the healthy elderly -- The stem cell -- The role of telomeres -- The role of apoptosis -- Growth and transcription factors -- Microenvironment, stroma, and dendritic cells -- B cells and T cells -- Macrophages.

Neutrophils -- Qualitative defects in hematopoiesis: myelodysplasia -- Clonality and cytogenetic abnormalities -- Apoptosis in MDS -- The role of the immune system -- Angiogenic factors -- The role of the microenvironment -- The role of RB, TP53 and RAS -- Oxidative damage and mitochondrial mutations -- Telomeres -- A model -- Conclusions -- REFERENCES -- 9 Aging and hematopoietic stress -- Introduction -- Hematopoietic stress -- Hematopoietic stress in experimental animals -- Hematopoietic stress in humans -- Discussion -- REFERENCES -- 10 Introduxtion Immunoglobulin response and aging -- Introduction -- Structure, classes, and functions of immunoglobulins -- Antibody-secreting B cells: origin, lineage, activation, and survival -- An overview of the age-related changes in serum immunoglobulins -- Immunoglobulin response and aging -- Immunoglobulin response to infections and vaccines -- Age-related decline in Ig production to in. uenza vaccination -- Mechanisms for the age-related decline in immunoglobulin production in response to immunologic challenge -- Immune system overview -- Age-related changes in the immune system -- Three schools of thought on the age-related decline in antibody response to foreign antigens -- Age-related increase in autoantibodies -- ACKNOWLEDGEMENTS -- REFERENCES -- 11 Biological and clinical significance of monoclonal gammopathy -- Introduction -- Epidemiology -- Biology of MGUS and the role of various cytokines -- Role of IL-6, IL-6R, IL-1beta, and TNF-alpha -- IL-6 and bone-marrow angiogenesis -- Role of HHV-8 -- Relationship between aging and the development of monoclonal gammopathy -- Diagnosis and follow-up of patients with MGUS -- Natural history and predictors of progression -- Summary -- REFERENCES -- PART III Anemia of aging -- 12 Erythropoietin and aging -- Introduction -- Erythropoiesis.

Erythropoietin physiology -- Erythropoiesis with aging -- Erythropoietin receptors -- Non-marrow activity of erythropoietin and erythropoietin receptors -- Normal erythropoietin response to anemia -- Relative erythropoietin deficiency -- Erythropoietin levels in the elderly -- Non-anemic elderly -- Endogenous EPO response to anemia in the elderly -- Studies in anemic elderly -- EPO responsiveness in the elderly with anemia: conclusions -- Serum EPO and hemoglobin changes with aging -- Understanding the relative EPO deficiency in the elderly -- Exogenous (pharmacologic) therapy with erythropoiesis-stimulating proteins -- Pharmacologic erythropoietin -- Response of elderly to ESPs -- Disease-specific indications -- Adjunct for autologous red-blood-cell donation -- Renal insufficiency -- Cancer-related anemia -- Conclusions -- REFERENCES -- 13 Iron and aging -- Iron is an essential trace element -- Iron homeostasis in humans -- Molecular mechanisms of iron transport -- Molecular mechanisms of systemic iron homeostasis -- Inflammation and iron -- Hereditary hemochromatosis -- Disorders of iron metabolism in the elderly -- Epidemiology of iron disorders in the elderly -- Conclusion -- REFERENCES -- 14 Prevalence and mechanisms of B12 deficiency -- Introduction -- Causes of vitamin B12 deficiency -- Megaloblastic anemia due to vitamin B12 deficiency -- Diagnosis of vitamin B12 deficiency -- Use of methylmalonic acid in the diagnosis of B12 deficiency -- Vitamin B12 replacement therapy -- Prevention of vitamin B12 deficiency in seniors -- Health effects of hyperhomocysteinemia and vitamin B12 deficiency -- REFERENCES -- 15 Consequences of chronic anemia in the older person -- Introduction -- Epidemiology and causes of anemia in older age -- Definition of anemia -- Prevalence and incidence of anemia in the older aged person -- Causes of anemia in the aged.

Consequences of anemia -- Anemia and mortality -- Anemia and functional dependence -- Anemia and therapeutic complications -- Anemia and heart disease -- Anemia and geriatric syndromes -- Should anemia always be treated? -- REFERENCES -- 16 Introduxtion The pathogenesis of late-life anemia -- Introduction -- Definition and prevalence of anemia in the elderly -- "Explained" anemia in the elderly -- Anemia of chronic inflammation (ACI) -- Renal insufficiency and anemia -- Myelodysplasia -- "Anemia unexplained" (AU) -- Androgens and aging -- Cytokines and aging -- Interleukin 6 (IL-6): a prototype mediator of age-associated anemia -- Age-associated changes in IL-6 -- IL-6 and anemia -- Cytokines and iron transport -- Cytokines and hematopoiesis -- Summary -- REFERENCES -- 17 Treatment of late-life anemia -- Anemia in geriatric populations -- Treatment of anemia in the elderly: general concepts -- Allogeneic red cell transfusion -- Erythropoietin -- Erythropoietin responsiveness -- rHuEPO for the treatment of anemia -- Erythropoietin in the central nervous system -- Erythropoietin safety -- Treatment of "anemia unexplained" -- Summary -- REFERENCES -- Part IV Hematologic malignancies and aging -- 18 Cancer chemotherapy in the older person -- Introduction -- Pharmacologic changes of aging -- Pharmacokinetics -- Pharmacodynamics -- Decreased functional reserve of normal organ systems -- Myelotoxicity -- Mucositis -- Cardiotoxicity -- Neurotoxicity -- Guidelines for the management of older individuals receiving cytotoxic chemotherapy -- Geriatric assessment -- Dose adjustment to the GFR -- Prophylactic use of filgrastim and pegfilgrastim -- Maintenance of hemoglobin around 12 g/dL -- Selection of drugs of low toxicity -- Age and targeted cancer therapy -- Conclusions -- REFERENCES -- 19 Introduxtion Acute myeloid leukemia in the elderly -- Introduction.

Unique challenges to treating AML in the elderly.