دانلود کتاب Biology of Aging

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Copyright Page\nPreface\nAcknowledgments\nDetailed Contents\nChapter 1: Basic Concepts in the Biology of Aging\n Biogerontology: The Study of Biological Aging\n Biologists began studying aging when human life spans increased\n Biogerontology became an independent field of research during the 1940s\n Current aging research considers the health of the total person\n Biological aging in nonhuman species shares many of the traits observed in human aging\n The study of aging is a complex process\n Definitions of Biological Aging\n The first definitions of biological aging were based on mortality\n Functional-based definitions help describe biological aging over specific time periods\n A definition of aging for Biology of Aging\n Development, maturity, and senescence are event-related stages used to describe aging\n Biological aging is distinct from the diseases of old age\n How Biogerontologists Study Aging: The Use of Laboratory Organisms in Human Aging Research\n Isolated cell systems can be studied to describe the basic biochemistry of aging and longevity\n Fungi are good models for studying environmental factors that affect aging and longevity\n Primitive invertebrates may provide clues to extended cellular life, cell signaling, and whole-body aging\n Insects can be used to investigate how whole-body and intracellular signaling affect life history\n Mice and rats are common research subjects in the investigation of nutritional, genetic, and physiological questions\n Nonhuman primates display many of the same time‑dependent changes as humans\n Human progerias can be used to model normal human aging\n How Biogerontologists Study Aging: Comparative Biogerontology\n Species’ body size is related to maximum life span\n Reduced vulnerability to extrinsic dangers explains extended longevity\n A highly organized social structure also extends longevity in the wild\n A few aquatic animals have extreme longevity\n Essential Concepts\n Discussion Questions\n Further Reading\nChapter 2: Measuring Biological Aging\n Measuring Biological Aging in the Individual\n Differences in the age-related phenotype affect the measurement of aging in individuals\n Lifestyle choices significantly affect phenotype\n The epigenome can also affect the rate of aging and longevity\n Cross-sectional studies compare changes in different age groups at a single point in time\n Longitudinal studies observe changes in a single individual over time\n Personal genomics will probably be the key to determining and applying biomarkers for aging\n Measuring Biological Aging in a Population\n Mortality rates estimate the number of deaths in populations\n Life tables contain information on mortality, life expectancy, and the probability of dying\n Age-specific mortality rate rises exponentially\n Age-independent mortality can affect the mortality rate\n Mortality-rate doubling time corrects for differences in initial mortality rates\n Survival curves approximate mortality rate\n Deceleration of mortality rate at the end of life suggests the possibility of longevity genes\n Essential Concepts\n Discussion Questions\n Further Reading\nChapter 3: Evolutionary Theories of Longevity and Aging\n Foundations of Evolutionary Theories of Longevity and Aging\n Weismann established the separation between soma and germ cells\n Weismann proposed that aging is a nonadaptive trait\n Population biologists developed logistic equations to calculate population growth\n A population’s age structure describes Darwinian fitness in complex eukaryotes\n Reproduction rate describes age-specific fitness in breeding populations\n Fisher described the relationship between reproductive potential and Darwinian fitness in populations\n Evolution and Longevity\n The extrinsic rate of aging leads to a decline in the force of natural selection\n Medawar theorized that aging arose as a result of genetic drift\n Medawar proposed that aging and longevity arise separately in post-reproductive populations\n Hamilton’s force of natural selection on mortality refined Medawar’s theory\n Testing Evolutionary Models of Longevity\n Late-reproducing organisms have a lower rate of intrinsic mortality\n Genetic drift links life span to reproduction\n Results from testing the evolutionary theory of longevity have changed research in biogerontology\n Evolution and Aging\n Antagonistic pleiotropy is a special case of general pleiotropy\n The disposable soma theory is based on the allocation of finite resources\n Essential Concepts\n Discussion Questions\n Further Reading\nChapter 4: Cellular Aging\n The Cell Cycle and Cell Division\n The cell cycle consists of four phases plus one\n DNA replication occurs during the S phase\n Cell division occurs during the M phase\n Regulation of the Cell Cycle\n S-cyclins and cyclin-dependent kinases initiate DNA replication\n The p53 pathway can prevent DNA replication at the G1‑to-S phase transition\n Many proteins are involved in the replication of DNA\n Cohesins and condensins help control chromosome segregation\n The metaphase-to-anaphase transition marks the final checkpoint in the cell cycle\n Fully functional cells can exit the cycle at the G0 phase\n Replicative Senescence\n A mistake delayed the discovery of cell senescence for 50 years\n Hayflick’s and Moorhead’s research findings created the field of cytogerontology\n Cells in culture have three phases of growth\n Senescent cells have several common features\n Replicative senescence can be used to describe biological aging\n The Cause of Cellular Aging: Accumulation of Damaged Biomolecules\n Biomolecules are subject to the laws of thermodynamics\n Life requires the constant maintenance of order and free energy\n The mechanism underlying aging is the loss of molecular fidelity\n Aging reflects the intracellular accumulation of damaged biomolecules\n Oxidative Stress and Cellular Aging\n Oxidative metabolism creates reactive oxygen species\n Mitochondrial ATP synthesis produces the majority of superoxide ions\n Enzymes catalyze reduction of the superoxide radical to water\n Cytosolic reduction also generates free radicals\n Oxygen-centered free radicals lead to the accumulation of damaged biomolecules\n Cell membranes are susceptible to damage by reactive oxygen species\n Reactive oxygen species can have beneficial effects\n Telomere Shortening and Replicative Senescence\n Telomeres prevent the lagging strand from removing vital DNA sequences\n Shortening of the telomere may cause somatic cell senescence\n Essential Concepts\n Discussion Questions\n Further Reading\nChapter 5: Genetics of Longevity\n Overview of Gene Expression in Eukaryotes\n Transcription of DNA produces complementary RNA\n Eukaryotic cells modify RNA after transcription\n Translation is the RNA-directed synthesis of a protein\n Proteins can be modified or degraded after translation\n Regulation of Gene Expression\n Gene expression can be controlled by changing nucleosome structure\n Gene expression is controlled by binding of proteins to DNA\n Post-transcriptional mechanisms can also control gene expression\n Analyzing Gene Expression in Biogerontology\n Genetic analysis in biogerontology begins with the screening of mutants\n Identification of gene function requires DNA cloning\n The function of the gene can be partially determined from its sequence\n In situ hybridization can reveal a gene’s function\n Genetically altering organisms helps evaluate a gene’s impact on human longevity\n DNA microarrays are used to evaluate gene expression patterns at different ages\n Genetic Regulation of Longevity in S. cerevisiae\n S. cerevisiae reproduces both asexually and sexually\n Environmental conditions influence reproduction and life span\n Structural alteration in DNA affects life span\n The SIR2 pathway is linked to longevity\n Loss-of-function mutations in nutrient-responsive pathways may extend the life span\n Genetic Regulation of Longevity in C. elegans\n Regulation of dauer formation extends life span\n Genetic pathways regulate dauer formation\n Weak mutations in the DAF-2 receptor extend life span\n Life extension is linked to neuroendocrine control\n Mitochondrial proteins may be the link between extended life span and metabolism\n Genetic Regulation of Longevity in D. melanogaster\n Drosophila has a long history in genetic research\n Genes that extend longevity are associated with increased stress resistance\n Genes controlling Drosophila’s growth also extend life span\n Genetic Regulation of Longevity in M. musculus\n Many M. musculus genes have been reported to affect longevity\n Decreased insulin signaling links retarded growth to longevity\n Diminished growth hormone signaling links insulin-like signaling pathways to increased longevity\n Genetic regulation of longevity demonstrated in mice has implications for human aging\n Essential Concepts\n Discussion Questions\n Further Reading\nChapter 6: Plant Senescence\n Basic Plant Biology\n Plant cells have a cell wall, a central vacuole, and plastids\n Photosynthesis takes place in the chloroplast\n Plant hormones regulate growth and development\n The Biology of Plant Senescence\n Mitotic senescence occurs in cells of the apical meristem\n Post-mitotic plant senescence involves programmed and stochastic processes\n Leaves of Arabidopsis thaliana are the model for plant senescence\n Leaf senescence is a three-step process\n Monosaccharides have an important role in leaf senescence\n Breakdown of the chloroplast provides nitrogen and minerals for other plant organs\n Catabolic by-products may stimulate expression of genes involved in organelle dismantling\n Plant membranes degrade during leaf senescence\n Initiating Plant Senescence\n Light intensity affects the initiation of plant senescence\n Cytokinins delay senescence\n Other plant hormones induce senescence\n Essential Concepts\n Discussion Questions\n Further Reading\nChapter 7: Human Longevity\n Origins of Human Longevity\n Human mortality rates are facultative\n Genetic factors cause significant plasticity in human mortality rates\n Mortality rates differ in long-lived humans\n Human intelligence has altered mortality rates\n Human intelligence has produced a unique longevity trajectory\n Heredity has only a minor influence on human life span\n The Rise of Extended Human Life Span in the Twentieth Century\n For most of human history, the average human life span was less than 45 years\n Control of infectious diseases increased mean life span\n Decreases in infant mortality increased life expectancy\n Improved medical treatments account for the continuing increase in life expectancy\n Essential Concepts\n Discussion Questions\n Further Reading\nChapter 8: The Physiology of Human Aging\n Changes in Body Composition and Energy Metabolism\n Energy balance is the difference between intake and expenditure\n Accumulation of fat occurs throughout maturity\n Excessive loss of body weight near the end of the life span increases mortality rate\n Sarcopenia is the age-related decline in skeletal muscle mass\n Changes in the Skin\n The skin consists of three layers\n Wrinkles are caused by a loss of skin elasticity and subcutaneous fat\n Ultraviolet light causes significant damage to the skin over time\n Changes in the Senses: Hearing, Vision, Taste, and Smell\n The sense of hearing is based on the physics of sound\n Transmission of sound through the human ear occurs in three steps\n Loss of stereocilia contributes to age-related hearing loss\n The sense of sight is based on the physics of light\n Presbyopia can be explained by age-related changes in the refractive power of the lens\n Terminal differentiation of lens cells leads to the formation of cataracts\n The senses of taste and smell change only slightly with age\n Changes in the Digestive System\n Age-related changes in the mouth and esophagus do not impair digestion\n Decline in stomach function is most often associated with atrophic gastritis\n Changes in the small intestine can affect digestion and nutrient absorption\n Changes in the Urinary System\n The kidneys remove metabolic waste products from the blood\n The kidneys help regulate blood pressure\n Renal blood flow and kidney function decline with aging\n Changes in the Immune System\n Innate immunity provides the first line of defense against infection\n Acquired immunity relies on lymphocytes reacting to antigens\n The phagocytotic function of neutrophils and macrophages declines with age\n The production of naive T cells, number of B cells, and effectiveness of antibodies all decline with age\n Changes in the Reproductive System\n Menopause is caused by declining secretion of sex hormones by the gonads\n Male fertility declines slightly with age\n Old age is not a barrier to sexual activity\n Essential Concepts\n Discussion Questions\n Further Reading\nChapter 9: Age-Related Disease In Humans\n The Nervous System and Neural Signals\n The nervous system is composed of neurons and supporting cells\n Membrane potentials establish the conditions for neural signal transmission\n Neurotransmitters chemically link neurons together at the synapse\n The human brain is a collection of separate organs and cell types\n Age-Related Diseases of the Human Brain: Alzheimer’s Disease and Parkinson’s Disease\n Changes in structure and neurotransmission seem to be minor in the aging brain\n Amyloid plaques and neurofibrillary tangles accumulate in the aged brain\n Alzheimer’s disease is an age-related, nonreversible brain disorder\n Alzheimer’s disease begins in the entorhinal cortex and progresses into the cortex\n The ε4 allele of the apolipoprotein E gene is a risk factor for late-onset Alzheimer’s disease\n Treatments for Alzheimer’s disease target neurotransmission and the prevention and degradation of amyloid plaques\n Parkinson’s disease is associated with loss of dopaminergic neurons\n Increasing the brain’s concentration of dopamine is the primary objective in treatment of Parkinson’s disease\n Lewy bodies are the pathological hallmark of Parkinson’s disease\n Several genes are associated with early-onset Parkinson’s disease\n Several factors may predispose individuals to Parkinson’s disease\n The Cardiovascular System\n The cardiovascular system is a closed system of fluid transport\n The heart and arteries are excitable tissues\n The heart controls blood flow and pressure by adjusting cardiac output\n Principles of fluid dynamics govern overall blood flow\n Age-Related Diseases of the Cardiovascular System: Cardiovascular Disease\n Environmental factors influence age-related decline in the cardiovascular system\n Arterial plaques can lead to atherosclerosis and ischemic events\n Risk factors for atherosclerosis are a mixture of genetic and environmental conditions\n Statins reduce the synthesis of cholesterol in the liver and lower serum cholesterol\n Hypertension is the most common chronic condition in the aged\n Heart failure results in a decline in cardiac output\n Prevalence is a better descriptor of cardiovascular disease than is mortality\n The Endocrine System and Glucose Regulation\n Blood glucose concentration must be maintained within a narrow range\n Insulin facilitates glucose uptake into liver, muscle, and adipose cells\n Age-Related Disease of the Endocrine System: Type 2 Diabetes Mellitus\n Insulin resistance is a precursor to type 2 diabetes\n Type 2 diabetes impairs microvascular blood flow\n Altered glucose metabolism may increase cell damage in people with type 2 diabetes\n Risk factors for diabetes include increasing age, obesity, and genetic background\n The Skeletal System and Bone Calcium Metabolism\n Parathyroid and thyroid hormones balance blood calcium\n Hormones regulate the balance between bone mineral deposition and resorption\n Age-Related Diseases of Bone: Osteoporosis\n An increased rate of bone mineral loss at menopause can lead to osteoporosis\n Environmental factors influence the risk of developing osteoporosis\n Drug therapies can slow bone loss in postmenopausal women\n Essential Concepts\n Discussion Questions\n Further Reading\nChapter 10: Modulating Human Aging and Longevity\n Modulating Biological Aging\n Aging cannot be modulated\n Mechanisms that lead to loss of molecular fidelity may be modulated in the future\n Modulating Longevity: Calorie Restriction\n Calorie restriction increases life span and slows the rate of aging in rodents\n Calorie restriction in simple organisms can be used to investigate genetic and molecular mechanisms\n Calorie restriction in nonhuman primates may delay age‑related disease\n The effectiveness of calorie restriction in humans remains unknown and controversial\n Modulating the Rate of Aging: Physical Activity\n Exercise increases the muscles’ demand for oxygen\n Overloading cellular oxidative pathways increases the capacity for ATP synthesis\n Regular physical activity prevents a decline in cellular reserve capacity\n Looking toward the Future: The Implications of Modulating Aging and Longevity\n Extended youth and the compression of morbidity will characterize aging in the future\n Long life may modify our perception of personal achievement and a progressive society\n Extended longevity may change our responsibility for renewal of the species\n Low birth rates and extended longevity may alter the current life cycle of generations\n The Future of Biogerontology\n Essential Concepts\n Discussion Questions\n Further Reading\nAppendix\nGlossary\nIndex