Aging Modern Theories and Therapies New Biology

232  AGING Homes%20Are%20Often%20Missed,%20Report%20Says&st= cse. Accessed September 4, 2009. Congressional investigators have discovered that nursing home inspectors are overlooking or minimizing serious problems, such as malnutrition and severe bed sores, that pose a threat to elderly patients. Schaffer, Amanda. “In Diabetes, a Complex of Causes.” New York Times. Available online. URL: http://www.nytimes. com/2007/10/16/health/16diab.html. Accessed July 18, 2009. This article profiles the work of Dr. Gerard Karsenty of Co- lumbia University, who has made some important discoveries regarding the onset of type II diabetes. Stein, Lisa. “Is Human Growth Hormone the Key to Eternal Youth?” Scientific American. Available online. URL: http://www. sciam.com/article.cfm?id=is-human-growth-hormone-t. Ac- cessed September 4, 2009. According to recent research, there is no proof to support the belief that growth hormone can reverse the aging process. U.S. Census Bureau News. “Older Americans Month: May 2009.” Available online. URL: http://www.census.gov/Press-Release/ www/releases/archives/cb09ff-07.pdf. Accessed July 29, 2009. Facts and figures regarding centenarians and people over 65. Wade, Nicholas. “Atlas Squeaked: A Complete Map of the Brain of a Mouse.” New York Times. Available online. URL: http://www. nytimes.com/2006/09/26/science/26brain.html?scp=1&sq=Atlas %20Squeaked:%20A%20Complete%20Map%20of%20the%20 Brain%20of%20a%20Mouse&st=cse. Accessed September 4, 2009. This articles profiles a $41 million project to map gene expression in specific neurons throughout the brain of a mouse. ———. “How Human Cells Get Their Marching Orders.” New York Times. Available online. URL: http://www.nytimes. com/2006/08/15/science/15skin.html?scp=1&sq=How%20 Human%20Cells%20Get%20Their%20Marching%20Orders&st =cse. Accessed September 4, 2009. When old cells in the human

Further Resources   233 body die, new ones form to take their place. This article de- scribes research that is attempting to explain how the new cells know where to go. Web Sites Department of Energy Human Genome Project (United States). Available online. URL: http://genomics.energy.gov. Accessed September 4, 2009. Covers every aspect of the human genome project with extensive color illustrations. Dr. Bob’s All Creature Site. “The Life Span of Animals.” Avail- able online. URL: http://www.sonic.net/~petdoc/life span.htm. Accessed September 4, 2009. This site is maintained by a veteri- nary hospital in California. Genetic Science Learning Center at the Eccles Institute of Hu- man Genetics, University of Utah. Available online. URL: http://learn.genetics.utah.edu/. Accessed September 4, 2009. An excellent resource for beginning students. This site contains information and illustrations covering basic cell biology, animal cloning, gene therapy, and stem cells. Google Video. Available online. URL: http://video.google.com/ videosearch?q=histology+tissue&emb=0&aq=3&oq=histology#. Accessed September 4, 2009. This site contains many videos covering human histology and cell biology. Institute of Medicine, Washington, D.C. Available online. URL: http://www.iom.edu/CMS/3710.aspx. Accessed September 4, 2009. This page of the institute’s Web site provides many reports dealing with the aging American population. Institute of Molecular Biotechnology, Jena / Germany. Available online. URL: http://www.imb-jena.de/IMAGE.html. Accessed September 4, 2009. Image library of biological macromolecules. National Center for Biotechnology Information (NCBI). Available online. URL: http://www.ncbi.nlm.nih.gov. Accessed September 4, 2009. This site, established by the National Institutes of Health,

234  AGING is an excellent resource for anyone interested in biology. The NCBI provides access to GenBank (DNA sequences), literature databases (Medline and others), molecular databases, and topics dealing with genomic biology. With the literature database, for example, anyone can access Medline’s 11,000,000 biomedical journal citations to research biomedical questions. Many of these links provide free access to full-length research papers. National Health Museum Resource Center. Washington, D.C. Available online. URL: http://www.accessexcellence.org/RC/. Accessed September 4, 2009. Covers many areas of biological research, supplemented with extensive graphics and animations. National Human Genome Research Institute. Available online. URL: http://www.genome.gov/. Accessed September 4, 2009. The institute supports genetic and genomic research, including the ethical, legal and social implications of genetics research. National Institute on Aging. Available online. URL: http://www. nia.nih.gov. Accessed September 4, 2009. A good source for research papers and news articles dealing with geriatrics, geron- tology, and Alzheimer’s disease. National Institutes of Health (NIH). Available online. URL: http://www.nih.gov. Accessed September 4, 2009. The NIH posts information on their Web site that covers a broad range of topics, including general health information, cell biology, aging, cancer research, and much more. Nature Publishing Group. Available online. URL: http://www. nature.com/nature/supplements/collections/humangenome/ commentaries/. Accessed September 4, 2009. The journal Nature has provided a comprehensive guide to the human genome. This site provides links to the definitive historical record for the sequences and analyses of human chromosomes. All papers, which are free for downloading, are based on the final draft produced by the Human Genome Project. Sanger Institute (United Kingdom). Available online. URL: http:// www.sanger.ac.uk. Accessed September 4, 2009. DNA sequenc-

Further Resources   235 ing center, named after Fred Sanger, inventor of the most commonly used method for sequencing DNA. The institute is also involved in projects that apply human DNA sequence data to find cures for cancer and other medical disorders. U.S. Census Bureau. Available online. URL: http://www.census. gov/. Accessed July 29, 2009. The site to visit for population statistics, such as the number of centenarians in the U.S. today and expected number by 2050. U.S. Food and Drug Administration. Available online. URL: http://www.fda.gov. Accessed September 4, 2009. Provides extensive coverage of general health issues and regulations. World Health Organization. Available online. URL: http://www. who.int/en. Accessed September 4, 2009. Extensive coverage of age-related issues throughout the world.

Index Note: Italic page numbers refer to illustrations. α-cells, pancreatic 99 Alzheimer, Alois 69 A Alzheimer’s disease (AD) 29, 68–82 Aakt-2 gene 61, 62 brain changes in 70, 71, 72, 73 Abbe, Ernst 15 clinical trials in 134, 135–139 acromegaly 144 diagnosis of 81, 81–82 actin filaments 154, 156 genes associated with 73–79 activity restriction 42 management of 112–113 Actonel 106–107, 148 preclinical 70, 71 adenine 159, 161–163, 164 progression of 71 adenosine triphosphate 156, 158, 167–168 amino acids 156–161, 157 adrenocorticotrophs 46 amplification, DNA 20 adrenocorticotropin (ACTH) 51 amyloid immunotherapy 136–138 Age-1 gene 61, 62 amyloid precursor protein 73, 77–79, 78, 80, age-related diseases 68–107. See also specific 81 diseases anaphase 170–171 aging. See also specific entries androgen supplements 53 andropause 142 characteristics of 29–35 anemia, sickle-cell 183 classical 30 aneuploidy 88 disease v. 29–34 angiogenesis 90 as evolutionary neglect xv, 38 animal cloning 12, 121–122, 125–127, 126, future directions in study of 13 healthy or successful 30 127 modern 30–34 animal life spans xv, 6–12 normal 30 antidiuretic hormone (ADH) 46, 51 physical appearance in xv–xvi, 12 antihistamines, in elderly 115 programmed, genes and 38–39 antioxidants 43, 135–136 theories of 19, 34, 36–54 ApoE gene 73, 79 aging mosaics 34–35, 133 apolipoprotein E 73, 79 aging process xiv apoptosis 90–91, 170, 174 aging society 109–110 APP gene 73, 77–79 Akt-1 gene 61, 62 arthritis 82–84, 83, 143 alendronate 106–107, 114, 148 atherosclerosis 92–100, 96, 97 atoms 151–153, 152 236

ATP synthase 167 Index   237 axons 70, 74, 75, 76 Azilect 149 C B Caenorhabditis elegans. See nematode calcium supplements 106, 114, 141 Bacillus acidophilus 16 Calment, Jeanne 11, 11, 30–31 bacteria caloric restriction 20, 42, 53–54, 63–64, evolution of 153 146–147 gene organization in 189 cancer 85–92 human genes obtained from 189 plasmids of 20, 174–176, 179 aging process and 88–90 structure of 153 cellular transformation in 85, 90–92 bacterial artificial chromosomes 187–188 hormone therapy and 84, 106 bacteriophage G4 genome 187 karyotypes of 86–88 bacteriophage lambda 176–177, 187 metastatic 85, 90–91 baker’s yeast 19–20. See also yeast carbenoxolone 145 bapineuzumab 137–138 cardiovascular disease (CVD) 92–98 base–flippers 165 clinical trials in 134, 139–142 bases, nucleotide 157, 159, 162–163 origin of life and 92–94, 93 beneficence 118 treatment of 98, 113 Berg, Paul 20 cell(s) beta-amyloid 77–79, 80, 81, 82, 135–138 basic functions of 163–173 β-cells, pancreatic 35, 99–100 biology of 151–173 biochemical theories of aging 36 communication of 57–58, 156, 163, 173 biomarkers of aging 31, 32, 33 division of 163, 168–173 Biomarkers of Aging Project 31 macromolecules of 159–163, 160 biotechnology 14, 20–26, 151, 174–182, molecules of 156–159, 157 as nature’s building blocks 151, 152 183 cell cycle 168–173, 169 bisphosphonates 106–107, 114, 148 cell fusion technology 128, 129 blotting, RNA 180–181 cell membrane 154, 163 bone(s) cellular differentiation 125 cellular senescence xiv, 13 health of 100–107 centenarians 11, 11, 31–34, 109 remodeling of 100, 103–104, 105 central nervous system structure of 103, 103 in Alzheimer’s disease 68–73 bone mineral density 104, 113–114, 148 components of 44, 69–70 Boniva 148 endocrine control by 43–46 Book of the Dead, The 4 centromere 171 brain 44, 69–70 centrosome 154, 168 as aging clock xvi cerebellum 44, 70 in Alzheimer’s disease 70, 71, 72, 73 cerebral cortex 70 weight of, and longevity 38 cerebral hemispheres 69 brain stem 44, 70 cerebrum 44, 69–70, 71 brain tumor 91 Chico gene 63–64 “brown bag” technique 111 Chinese medicine 17 burial practices 1–5, 2, 4 cholesterol 92, 94–97, 95 Butler, Robert 121 cholinesterase inhibitors 112–113 chromatids 171

238  AGING chromatin 171 cytosine 159, 161–163, 164 age-related changes in housefly 34 cytoskeleton 156 compaction or condensation of 24–26, D 25 function of 24 Daf-2 gene 60–61, 62, 66–67 chromosomes Daf-12 gene 61, 62, 67 bacterial artificial 187–188 Daf-16 gene 61, 62 chromatin and 24 Daf-18 gene 61, 62 damage, in cancer 87–88 Daf-23 gene 61, 62 eukaryotic 155–156 Darwin, Charles 10 in meiosis 172–173 daughter cells, production of in mitosis 171–172 telomeres of, and aging 39–41 damage checkpoints in 169, 170 chronological age 31 in meiosis 170, 172–173 citric acid (Krebs) cycle 15–16, 58, 99, 167 in mitosis 168, 170, 171–172 classical aging 30, 32 in yeast 56, 57 clinical trials 134–150, 190–192 deamination 165 cloned DNA labeling 177–178 De Grey, Aubrey 121 cloning dehydroepiandrosterone (DHEA) 23–24, 144 animal 12, 121–122, 125–127, 126, 127 dementia 112–113. See also Alzheimer’s controversy over 121–122 DNA 20, 174–176, 175 disease in rejuvenation therapy xvi, 12, 121–122, dendrites 70, 74, 75, 76 deoxyribonucleic acid. See DNA 125–127 depurination 165 cloning vector 176 deSilva, Ashi 185 coated pits 94, 95 diabetes 98–100 codons 166–167 Colman, Ricki 42 type I 100 complementary base pairing 162–163 type II 35, 100 complementary DNA (cDNA) 177 diapause state 60–61 compound B 82 diestrus 52 compound microscope 14, 15–16 dietary modification 141–142, 145–147 connective tissue 101, 101–103, 102 disaccharides 163 consent, informed 118–119, 190 disease(s). See also specific diseases constitutive expression 21 age-related 68–107 contact inhibition, in cancer 90 v. aging 29–34 contigs 188 DNA 156, 162–165 corpus callosum 69 cloning of 20, 174–176, 175 cortisol inhibition 145 complimentary 177 creams, anti-aging 5 damage checkpoints for 169, 170 Crick, Francis 17, 18 enzymes modifying 174–177 Cro-Magnons, burial practices of 1–3, 2 fluorescent in situ hybridization of 180, Ctl-1 gene 61, 62 Curie, Marie 5 181 cytochrome b 167 functions of 163 cytochrome oxidase 167 identification of 16 cytokinesis 171 maintenance/repair of xv, 163, 164–165 cytoplasm 154, 155 nucleotides in 159, 160 polymerase chain reaction in 177, 180, 181–182

Index   239 recombinant 14, 20–26, 151, 174–182, 183 embryonic stem cells 130 replication of 17, 163, 164 endocrine system 43–46, 45 and DNA sequencing 178–179 in regulation of aging 34, 36, 43–54 errors in, and aging 19, 36–37 self-regulation of 48 Hayflick limit of 40–41 endocytosis 94 and labeling cloned DNA 177–178 endoplasmic reticulum 154, 155–156 telomeres and 39–41, 40 Energy, Department of 26–27, 183 sequencing of 20–26, 175, 177, 178–179, enhancers, gene 177 enzymes, restriction 174–177, 175 187–188 error catastrophe theory 19, 36–37, 39 structure of 14, 17, 159, 160, 163 Escherichia coli 174–176, 187 transcription of 18–19, 21, 36–37, 166, estren 106 estrogen 189–190 age-related decline in 23–24, 52, 142 DNA amplification 20 and Alzheimer’s disease 69 DNA helicase 164 and bone health 100, 105, 106, 143, 149 DNA libraries 174, 175, 176–177 and cancer 106 DNA ligase 174, 176 and cardiovascular disease 141 DNA microarray analysis 123–125, 124 and dementia 113 DNA polymerase 39, 164, 177–179, 182 and ovarian cycle 48, 50 DNA primase 164 ratio with testosterone 90, 143 Dolly (cloned sheep) 125–127, 126 and rejuvenation 122 donepezil 113 supplements/replacement of 53, 142–145 Doonan, Ryan 43 estrous cycle 52 dopamine 149 Estruch, Ramon 142 double helix of DNA 14, 160, 163 ethical issues 117–119 eukaryotes Drosophila evolution of 153 error catastrophe theory in 37 gene organization in 189–190 expression studies in 21, 23–24 genome of 153 free radical theory in 61–62 structure of 153–156, 154 genome sequencing in 26–27 evolution hormone levels in 23–24 Darwin’s theory of 10 life span of xv, 6, 7, 38 of eukaryote cells 153 longevity genes in 27–28, 61–64, 66–67 of multicellular organisms 153 number of genes in 188 origin of life 92–94, 93, 153 as research subject 19–20 of prokaryote cells 153 evolutionary neglect, aging as xv, 38 drug history, patient 111 exercise 98, 107, 114, 147 drug therapy, geriatric 108–109, 115–116 exons 189–190 expression studies 20–26 E F EcoRI 174–176 Egyptians 3–5, 4, 17 fatty acids 157, 158 Ehrlich, Paul 16 female reproductive cycle 48, 50, 52 electron(s) 151 fibroblasts 101, 101, 102 electron microscope 19 Flamel, Nicholas 17 electron transport chain 156, 167–168 electrophoresis 21, 22, 178 elephants, life span of 6–7, 8 embryogenesis 29, 125

240  AGING flies. See Drosophila; Musca domestica genome sequencing 14, 26–28, 54, 55–56, 123, florbetapir 81, 82 187–190 fluorescent in situ hybridization 180, 181 follicle-stimulating hormone 48, 50, 51 genomic errors 37 Food and Drug Administration (FDA) 190–192 genomic libraries 176–177 Forteo 107, 148–149 geriatric patients Fosamax 106–107, 114, 148 fractures, osteoporotic 105–106 drug history of 111 Framingham Heart Study 139–140 drug therapy in 108–109, 115–116 free radical theory 19, 36, 42–43, 61–62, 135 evaluation of 110–112 fruit fly. See Drosophila managing age-related disorders in 112–115 medical history of 109, 111 G nutrition history of 112 geriatrics 108–119 galantamine 113 aging society and 109–110 Galápagos tortoise xv, 9, 9–10 clinical 109 gametes 172 definition of 108 Gap phases 168, 169, 170 ethical issues in 117–119 gel electrophoresis 21, 22, 175, 178 Geron Corporation 41 Gelsinger, Jesse 185 gerontologists, definition of xvi Gems, David 43 gerontology gene(s) first epoch of 14, 15–17 second epoch of 14, 17–20 codons and 166–167 third epoch of 14, 20–26 errors in, and aging 37 fourth (current) epoch of 14, 26–28, 55–56 eukaryotic 155 definition of xvi, 14 horizontal transfer of 189 gains expected in 13 human 188, 189–190 goals of 38, 55–56 longevity xvi, 27–28, 54, 55–67 history of 14–28 naming conventions for 192–193 questions in 15 organization of 189–190 trend in xvi and programmed aging 38–39 G4 genome 187 gene disregulation 57, 66, 67 Gilbert, Walter 20 gene expression 163, 166–167, 175, 180–182 ginkgo biloba 113, 138–139 chromatin and 24–26, 25 glucose 98–100, 157, 158 constitutive 21 glycerol 156, 157, 158 DNA microarray analysis of 123–125, 124 glycocalyx hormones and 23–24 in Alzheimer’s disease 77–79, 78 inappropriate, and aging 39 in cellular communication 57–58, 156, 173 regulative 21 in yeast 57–58 studies of 20–26 glycosylated APP (gAPP) 80 gene therapy 182–185, 184, 186 Golgi, Camillo 16 for Alzheimer’s disease 138 Golgi apparatus 16, 154, 156 for rejuvenation 131–132 Golgi vesicles 72, 76 genetic code 17–20, 166–167 gonadotrophs 46 genetic stability 57, 66, 67 gonadotropin-releasing factor 48 in human 66, 67 growth and development 29 in yeast 57, 60, 67 growth hormone (GH) 51 genetic theories of aging 36 age-related decline in 23–24, 142 cells producing 46, 47

Index   241 in mouse, genes and 64 human longevity genes 65–66 supplements of 53, 143–145 hybridization 180–181 tumors producing 86 hypertension, management of 113 growth hormone-releasing hormone 145 hypothalamus 44, 45 guanine 159, 161–163, 164 in regulation of aging 34, 52–53 in regulation of endocrine system 45, 46 H I Harman, Denham 19 ibandronate 148 Haversian canals 103, 103 immortality, quest for 1–13 Hayflick, Leonard 40–41 Hayflick limit 40–41 rejuvenation and 120 Hda-1 gene 59–60, 67 scientific 5–6 healthy aging 30 spiritual 1–5 hearing 31 incontinence 114–115 heart 35 Indy gene 62–63, 66–67 HeLa cell 128, 129 informed consent 118–119, 190 hierarchical shotgun sequencing 187–188 Inr gene 63–64 high-density lipoproteins (HDL) 94–98 Institute of Medicine (IOM) 116, 117 hip fractures 105–106, 148 insulin 35, 63–64, 99 hippocampus 44, 70, 71 insulin-like growth factor 23–24, 107 Hippocratic oath 118 insulin-like receptor 60–61 histochemistry 16 International Committee on Standardized histology 16 histone(s) 24, 170 Genetic Nomenclature 192 histone deacetylase 59–60 interphase 24, 168–170, 169 homologous chromosomes 172–173 intervening sequences 177, 189 horizontal transfer of genes 189 interview, of geriatric patient 110 hormone(s) introns 177 age-related decline in 23–24, 31, 52–53, J 90, 101, 104–105, 142 Jazwinski, S. Michel 57 in cancer development 90 jumping genes 189 pituitary 45, 48, 49, 50, 51 in regulation of aging 36 K hormone extracts 17 hormone replacement therapy 142–145 karyotypes 86–88, 87 hormone therapy 53 Keys, Ancel 146 for arthritis 84 kinetochores 171 for cardiovascular disease 141–142 Klunk, William 81–82 health risks with 84, 106, 143 Krebs, Hans 15–16 for osteoporosis 106, 114, 148–149 Krebs cycle 15–16, 58, 99, 167 for rejuvenation 122 housefly. See Musca domestica L human genome 26–28, 54, 123, 187–190 Human Genome Organization 26–27, 187 labeling, of cloned DNA 177–178 Human Genome Project 123, 187–190 lactic-acid bacteria, and aging 16–17 human growth hormone. See growth hormone lactotrophs 46 human life span xv, 6, 11, 38

242  AGING Lag-1 gene Mathis, Chester 81–82 human homolog of 65, 67 maturation promoting factor 168–170 in yeast 57–58, 59, 66–67 McGrath, James 122 measures 193 lambda bacteriophage 176–177, 191 Medicaid 110, 116 leptons 151, 152 medical history, patient 109, 111 leukemia 85–86, 88, 89, 89–90 Medicare 110, 116 levodopa 149 Mediterranean diet 142, 145–147 life, origin of 92–94, 93, 153 meiosis 168, 170, 172–173 life span meiosis I 172 meiosis II 172–173 comparison of animal xv, 6–12 melanocyte-stimulating hormone (MSH) 46 experimental manipulation of 19–20, 42 men, aging characteristics in xv–xvi genes and 38 menopause 52, 69, 90, 105, 142 human xv, 6, 11 messenger RNA (mRNA) 17–19, 37, 155–156, natural selection and xv, 15 normal, production of 56 189–190 lifestyle 113, 145–147 in DNA library construction 177 light microscopy 16 in DNA microarray analysis 123–125, 124 lipoprotein(s) in expression studies 21, 166 circulatory transport of 94–97 metabolic burnout 35 excess, in cardiovascular disease 92 metabolic control 57, 65–66 origin of life and 92–94, 93 in fruit fly 61–64, 66–67 liposomes, as vector 132–133, 183 in mouse 64, 66–67 longevity genes xvi, 27–28, 54, 55–67 in nematode 60–61, 66–67 in fruit fly 27–28, 61–64, 66–67 in yeast 57, 66–67 in human 65–66 metaphase 170–171 in mouse 64–65, 66–67 metaphase checkpoint 169 negative regulators of life span 56 metaphase plate 171 in nematode 27–28, 60–61, 62, 66–67 metastasis 85, 90–91 positive regulators of life span 56 Metchnikoff, Elie 16–17 in yeast 27–28, 56–60, 57, 66–67 microarray analysis 123–125, 124 lovastatin 98 microscope(s) low-density lipoprotein (LDL) 92, 94–97, 95, compound 14, 15–16 electron 19 98 light 16 lung cancer 89–90 microtubules 23, 154, 169–170, 171 luteinizing hormone (LH) 48, 51 mitochondria 154, 156, 167, 191 lysosomes 154, 156 mitosis (cell division) 168, 169, 170–171, 172 lysozyme 161 mitotic spindle 169–171 modern aging 30–34 M molecules 151, 152 of cell 156–159, 157 Macbeth (fictional character) 6 in origin of life 153 macromolecules 152, 153, 159–163, 160 monkeys, caloric restriction in 42, 53–54, 146 macrophages 97–98 monoamine oxidase (MAO) 149, 189 “magic potions” 17 monosaccharides 158, 160, 163 Malpighian tubule 34 mother cell 56, 57 maltose permease 64 motor proteins 171 MAO gene 189 Martin, George 121

Index   243 mouse nuclear envelope 169–170, 171 cessation of estrous cycle in 52 nuclear pore 154 error catastrophe theory in 37 nuclear rejuvenation therapy (NRT) 123 free radical theory in 43 nuclear transfer technology 125–127 genome sequencing in 26–27 nucleic acids 158 longevity genes in 64–65, 66–67 nucleolus 154 as research subject 19–20, 65 nucleosome 24 nucleotides 157, 159, 160, 162–163 M phase 168, 169, 170 nucleus 153, 154, 155 mRNA. See messenger RNA nursing homes 116–117 Mth gene 62, 63, 67 nutrition 141–142, 145–147 multicellular organisms nutrition history, patient 112 evolution of 153 O senescence in 15 Musca domestica 19, 34 oldest person, world’s 11, 11 muscles, aging of 34 oligosaccharides 163 Myc gene 192–193 Olshansky, S. Jay 120–121 myelocytomatosis 86 oncogenes 23, 85 oncologists 85 N one-gene-one-protein hypothesis 18–19 organelles 153 NADH dehydrogenase 167 organ systems xvi National Institute of Aging (NIA) 27–28, 31, Orgel, Leslie 19 origin of life 92–94, 93, 153 55, 135–136, 147 osteoarthritis 84, 143 National Institutes of Health (NIH) 106, 134, osteoblasts 100, 101, 103, 104, 106–107 osteoclasts 100, 104, 105, 106–107 140, 190–192 osteons 103, 103 National Research Council 26–27, 187 osteoporosis 31, 100–107 natural selection, and life span xv, 15 nature’s building blocks 151–153, 152 clinical trials in 134, 148–149 negative regulators, of life span 56 diagnosis of 113–114 nematode treatment of 106–107, 113–114 osteoprotegerin 104, 106 free radical theory in 43 osteosarcoma 107 genome sequencing in 26–27 ovarian cycle 48, 50, 52 longevity genes in 27–28, 60–61, 62, 66–67 oxidative phosphorylation 43 number of genes in 188 oxygen free radical 43 neural growth factor (NGF) 138 oxytocin 46, 51 neuroendocrine system 43–46, 45 neuroendocrine theory 34, 43–54 P neurofibrillary tangles 77 neurons P66shc gene 65, 66, 67 aging of 34 pancreas 99 communication among 70–73, 74, 75 pancreatic α-cells 99 neurotransmitters 72–73, 76 pancreatic β-cells 35, 99–100 neutrons 151 parathyroid hormone 106–107, 148–149 New England Centenarian Study 32–34 Parkinson’s disease 134–135, 149–150 nicotinamide adenine dinucleotide (NAD) 167–168 nitrogenous bases 159 normal aging 30

244  AGING Pasteur, Louis 5 of meiosis I 172–173 peptide bonds 159 of mitosis 170–171 peroxisomes 154, 156 protein(s) 156 phase I clinical trial 190–191 complexity in humans 188 phase II clinical trial 191 errors in, and aging 19, 36–37 phase III clinical trial 191 expression studies of 20–26 phase IV clinical trial 191–192 glycosylation of, in diabetes 100 phenotype motor 171 naming conventions for 192–193 of aging xv–xvi structure of 159–161, 160 conversion from aged to youthful 12–13 synthesis of 17–20, 155–156, 163, 166 Philadelphia chromosome 88, 89 protein electrophoresis 21, 22, 175, 178 philosopher’s stone 17 protons 151 phosphate 156, 157, 158, 159 protozoans, lack of aging in xiv, 15 phospholipid(s) 156, 163 purine 157, 159 and origin of life 92–94, 93 pyrimidine 157, 159 structure of 160, 163 physical appearance, aging and xv–xvi, 12 Q physiological age 31 physiological theories, of aging 36 quarks 151, 152 Pit-1 gene 64, 66 pituitary gland 44, 45 R cells of 46–48, 47 as master gland 46 radioactive cocktails 5 tumors of 86 Ramón y Cajal, Santiago 16 pituitary hormones 45, 48, 49, 50, 51 random primer labeling 178 plasmids 20, 174–176, 179 Ras-1 gene 58, 59 polymerase chain reaction (PCR) 177, 180, Ras-2 gene 58, 59, 67 rat(s) 181–182 polyploidization 163 cessation of estrous cycle in 52 polysaccharides 156, 160, 163 free radical theory in 43 positive regulators, of life span 56 as research subject 19–20 post-genomic era 14, 26–28 rate-of-living theory 41–42 postmitotic cells 168 receptors 173 Potter, Harry (fictional character) 17 Recombinant DNA Advisory Committee 190 preclinical research 190 recombinant DNA technology 14, 20–26, 151, presenilin 73, 77–79 primary transcript 190 174–182, 183 progestin 141 regulative expression 21 programmed aging, genes and 38–39 rejuvenation xvi, 5, 12–13, 120–133 prokaryotes cell fusion technology in 128, 129 aging process lacking in xiv controversy over 120–122 evolution of 153 DNA microarray analysis in 123–125, gene organization in 189 genome of 153 124 structure of 153 gene therapy in 131–132 prolactin 51 liposome delivery of therapy 132–133 promoters, gene 177 nuclear transfer technology in 125–127 Prop-1 gene 64, 66 nucleus as focus in 123 prophase stem cell analysis in 128–131 telomerase and 41

Index   245 replication of DNA. See DNA, replication of senilin 73, 77–79 replicative senescence 39–40 senility, disease v. aging in 29 reproductive cycle, female 48, 50, 52 SENS protocol 121 respect for persons 118 Sgs-1 gene restriction enzymes 174–177, 175 retinoic acid 5 human homolog of 66, 67 retrograde response 58, 62–63 in yeast 59, 60, 67 reverse transcriptase 177 Shakespeare, William xiv, 6 rhesus monkeys, caloric restriction in 42, sheep, cloned 125–127, 126, 127 Shh gene 192 53–54, 146 shotgun sequencing, hierarchical 187–188 rheumatoid arthritis 83, 84 sickle-cell anemia 183 ribonucleic acid. See RNA Sir-2 gene 59–60, 67 ribonucleotides 161 sister chromatids 171 ribose 157, 158, 159 skin, aging of 31 ribosomal RNA (rRNA) 59, 60, 166 skin cancer 86 ribosomes 154, 155–156, 162, 166 Skovronsky, Daniel 82 risedronate 106–107, 148 Sod-1 gene 61–62, 63, 66–67 risk factors 140 Solter, Davor 122 rivastigmine 113 somatic cells, chromosomes in 172 RNA 156, 161 somatotrophs 46, 47 Spemann, Hans 125 functions of 163 spinal cord 44, 69 messenger. See messenger RNA 30S ribosomal unit 162 nucleotides in 159, 160 stem cell analysis xvi, 12, 128–131 ribosomal 59, 60, 166 stem cells 130, 131 structure of 159, 160, 161 “strategies for engineered negligible senescence” transcription to 18–19, 21, 36–37, 166, (SENS) 121 189–190 stress resistance 57, 66, 67 transfer 17–18, 166 translation of 18–19, 21, 36–37, 122, 166, in fruit fly 62 in mouse 64–65 189–190 in nematode 61 RNA blotting 180–181 in yeast 57, 58 RNA polymerase 166 sturgeon, life span of xv, 7–9 Rowling, J. K. 17 subatomic particles 151 Rpd-3 gene 59–60, 67 successful aging 30 Rudman, Daniel 23, 143–145 sugar(s) 151–153, 157, 158 Sugar baby gene 63–64 S superoxide dismutase (SOD) 43, 61–62 SV40 virus 187 Saccharomyces cerevisiae. See yeast synapse 70, 75, 76 Sanger, Fred 20, 178–179, 187 synaptic junction 70, 76 Sanger sequencing method 178–179, 187 synaptic transmission 70–73, 75, 76 Schneider, Anton 16 second messenger 173 T senescence 29 Tau gene 73–77, 79 cellular xiv, 13 telomerase 41 in multicellular organisms 15 telomeres 39–41, 40, 53 replicative 39–40 telophase 170–171 study of, problem with 29 Sen gene 73, 77–79

246  AGING testosterone V and bone health 100, 105 ratio with estrogen 90, 143 vasopressin. See antidiuretic hormone and rejuvenation 122 vectors supplements/replacement of 53, 142–143 cloning 176 theories of aging 36–54 gene therapy 183–185, 184, 186 biochemical 36 rejuvenation therapy 132–133 error catastrophe 19, 36–37, 39 vertebral fractures 105–106, 148 free radical 19, 36, 42–43, 61–62, 135 viral vectors 183–185 genetic 36 vision 31 neuroendocrine 34, 43–54 vitamin A 5 physiological 36 vitamin B 136 rate-of-living 41–42 vitamin C 43, 135–136 telomere 39–41, 40 vitamin D 106, 114, 141, 149 vitamin E 43, 113, 135–136 30S ribosomal subunit 162 Tho-Radia 5 W thymine 159, 162–163, 164 thyroid gland, regulation of 48, 49 Watson, James 17, 18 thyroid hormone 23–24, 46, 64 weights and measures 193 thyroid-stimulating hormone 48, 49 Weindruch, Richard 42 thyrotrophs 46 Weismann, August 15 thyrotropin 48, 49, 51 Werner’s syndrome 28, 37, 66, 67 thyrotropin-releasing hormone 48, 49 white blood cells, in atherosclerosis 97–98 T lymphocytes, in atherosclerosis 98 Wilmut, Ian 125–127 tolterodine 114–115 witchcraft 17 tortoise, life span of xv, 9, 9–10 women, aging characteristics in xv–xvi transcription 18–19, 21, 36–37, 166, 189–190 Women’s Health Initiative 140–142, 143 transfection 174 Wright, Orville 121–122 transfer RNA (tRNA) 17–18, 166 Wright, Wilbur 121–122 transformation, in cancer 85, 90–92 Wrn gene 66, 67 translation 18–19, 21, 36–37, 122, 166, Y 189–190 transposable elements 189 yeast tRNA. See transfer RNA budding of 57 truncated APP (tAPP) 77–79, 80 genome sequencing in 26 tumor(s) life span of 56 longevity genes in 27–28, 56–60, 57, 66–67 brain, imaging of 91 as research subject 19–20 formation of 85, 90 tumor suppressor genes (TSGs) 85 younger, growing 12–13. See also rejuvenation Tuszynski, Mark 138 Tutankhamum (Egyptian king) 3, 4 U Z uracil 159, 161 Zandi, Peter 135