ethical issues: bioethics and, 264–65; sustainability and, 262–63
ethyl methanesulfonate, 178
Euripides, 238
euthanasia, 257–58, 259
evolution, 194; absence of predators and, 185–87; of aging, 83–84, 87–116, 117, 146, 178, 182–84, 185–88, 196, 242–44; calorie restriction and, 187–88; of life on Earth, 87–88; of mortal animals, 242–44. See also natural selection evolutionary biology, 175–76, 180, 181–85; Methuselah breeding and, 182–84; skin-out vs. skin-in approach and, 175–76, 180, 181–82, 184, 185, 188, 265
“Experience” (Montaigne), 223
experimental science, 139–40
eyesight. See vision
famine, adaptive responses to, 192
Fantastic Voyage (Kurzweil), 274
fibrodysplasia ossificans progressiva, 83
Finch, Caleb, 103–4, 105, 163
Finkel, Toren, 128
Fitzgerald, F. Scott, 268, 269, 270
Fitzwilliam Museum, Cambridge, England, 224–25
floaters, 173
Forlì, Italy: author’s trip with de Grey to, 209–12; de Grey’s epiphany in, 201–3, 207, 211–12
Fortune, 210
Franklin, Benjamin, 36–37, 38, 43, 235
free radicals, 77–79, 82, 83, 118, 131, 143
Freud, Sigmund, 40, 92
fruit flies, 39, 49, 136; Methuselahs, 181, 182–85, 188
Galileo, 225–27, 240–41
Garbage Catastrophe, 17–18, 117–74, 243, 277–79; bioremediation and, 133–36, 137–39, 141; coining of term, 144; creation-destruction balance and, 118, 128–29, 132, 142–43; de Grey’s junk list and, 149–61 (see also Seven Deadly Things); and doubling of mortality rate every eight years, 162–63; junk as by-product vs. cause of disease and, 173–74; late-onset diseases and, 142; laying down of damage in early life and, 162, 163; lysosomes and, 126–27, 128, 130–32, 133, 142–44, 173; three possible approaches to, 124–26, 146–48, 169; vision problems and, 121–24, 126, 172–74. See also disposable soma theory
gems, buying eternity in, 241
Gems, David, 261–62
genes: calorie restriction and, 188–89; cleansing of all genetic damage, 278–79; disposable soma theory and, 102–3, 118; dying without passing on, 94–96; evolutionary Methuselahs and, 183–84, 185–86; housekeeping, 128–30; late-onset diseases and, 96, 98–100, 101; longevity, Methuselah mutants and, 178–82, 185, 188; longevity, passing on of, 106–7; natural selection and, 94, 97–101, 105; shifts of, when two living things become closely intertwined, 153–54; for telomerase, elimination of (WILT procedure), 202–7. See also DNA; mutations
Genesis, 237–40. See also Adam and Eve
gene therapy, 155
Georgian era, 10–11
germ cells, 244; immortality of, 91; mutations in, 177
gerontology, 13–17, 19–20, 22–23; de Grey’s disdain for, 170–71, 207–9; disagreements over goals of, 276–79; image and public-relations problems of, 128, 145; increased interest in, 13–14; origin of word, 14, 41; other scientists’ views on, 48, 49–50, 54.
See also specific topics
Gilgamesh, 26–27, 44, 239
global graying, 234–35
God, 13, 27, 32, 33, 271; Abraham’s sacrifice and, 237–40
gold, drinking of, 34
Golgotha (Calvary), 238–39
Gould, Stephen Jay, 176
Graham, A. C., 261
Grandmother Hypothesis, 106–11; longevity advancement in Upper Paleolithic and, 108–9; menopause and, 109–11; Paleolithic dental record and, 107–8
grandparents: in Paleolithic, 107–9; passing on of longevity genes and, 106–7
graveyards, soil microbes in, 134–36, 138–39, 141
Greek mythology, 27–28, 249–50; Hydra story in, 120, 160–61, 250
Greenfield, Debra, 271
Gruman, Gerald, 28, 29
Guarente, Leonard P., 188–89, 273–74
guts, 73, 124, 157, 243; bacteria in, 39, 153–54; telomerase elimination and, 203, 204, 206, 207
Haeckel, Ernst, 248
Haldane, J.B.S., 196
Hamilton, William, 263, 265–66
Harman, Denham, 78, 79, 82
Harris, Sir Arthur Travers, 230–31
Hayflick, Leonard, 42–43
Hazzard, Shirley, 211
health, taking care of, 273–76
heart, 243; buildup of junk in, 124
heart attacks, 103, 204, 275
heart disease, 104, 198
Hecht, Michael, 158
Hercules, 120, 249–50
Hinduism, 239
History of Life and Death, The (Bacon), 33–35, 50, 58, 88, 114, 161–62
Hobbes, Thomas, 35–36
Holliday, Robin, 117–20
Homer, 28, 238, 240
hope, good for prolongation of life, 34
Houdetot, Madame d’, 235
Houellebecq, Michel, 279
housekeeping genes, 128–30, 132–33
human cells, 77; Carrel’s petri dish of, 42–43; division of, 42–43; mortal vs. immortal, 91; number and differentiation of, 73
human growth hormone (HGH), 264
human species (Homo sapiens), 244; genome and, 263–65; immortality and regime of, 262–65; sustainability issues and, 262–63
Huntington’s disease, 98, 99, 101, 195, 196, 277; rapamycin and, 192–93
Hydra, legend of, 120, 160–61, 250
hydras, 54–57, 59, 67, 119, 242, 243, 244, 256
hydrophobicity: mitochondrial DNA and, 154–55; nerve cells of brain and, 157–58
identical twins, 162, 274
identity, permanence of, 252, 253–54, 267
Iliad (Homer), 28
immortality, 25, 127, 239, 246–82; believed to be of no use to species, 89–91, 92–93; boredom issue and, 247–51; continual regeneration necessary for, 119, 256; desirability of, 169, 235, 236–37, 246–66; of first multicellular bodies, 242; of germ cells, 91, 244; of hydra, 54–57 (see also hydras); in legend and myth, 26–28, 246–47; persistence of regimes in science, art, and politics and, 259–62; of Phoenix, 71–72, 83; possibility of scientific breakthrough on, 17–19, 161–62, 235–37, 270–71; Raff’s perspective on, 254–59; regime of species and, 262–65; travel through seven ages of man and, 251–54. See also mortality
immune system, 118, 129, 142, 163, 164, 198, 199
Indy (I’m Not Dead Yet), 188
infants, 143; dependent on their mothers, 110–11; mortality of, 10, 12, 18. See also childhood
inflammation, 103–4, 105, 163
“Influence of a Sense of Time on Human Development, The” (Carstensen), 228–29
insects, 244
intelligence, 244–45
inventions, longer life resulting from, 43–44
Iphigeneia, 238, 240
Isaac, 237–40
Italy, graying of, 234
James, William, 156
James the First, King, 12–13, 31, 33
Janáek, Leoš, 249
Japan, life expectancy in, 232, 233
Jefferson, Thomas, 37
Jesus Christ, 71, 239, 263–64
Jewish scripture, legends, and proverbs, 27, 71, 246–47, 253, 281; Abraham’s sacrifice, 237–40
Johnson, Samuel, 11, 22, 230
Johnson, Tom, 179, 181
Journal of the American Medical Association, 42
Joy of Sex, The (Comfort), 64
junk. See Garbage Catastrophe Keats, John, 225
Kenyon, Cynthia, 180, 181, 184
kidney stones, 124
Kirkwood, Tom, 102–3, 274
Klass, Michael R., 178–79, 180, 181
Klatz, Ronald, 120
knowledge-gatherers, 110–11, 112
Ko Hung, 28–29, 33, 149
Kuang, Ssu-ma, 279
Kurzweil, Raymond, 274
Lansbury, Peter T., 19
4
Lashuel, Hilal, 194
late-onset diseases, 96, 98–100, 101, 142; solving all problems at once and, 155–56
Lederberg, Joshua, 266–67, 276
Lee, Sang-Hee, 107–9
Leonardo da Vinci, 52
Lewis, Ed, 49
Lewy bodies, 157, 193
life expectancy, 232–35; challenges resulting from changes in, 233–35; childbearing and, 164–65, 213, 240; defined, 12; further improvements expected in, 232–33; global graying and, 234–35; increases in, 10–12, 18, 43–44, 103, 108–9; limit on, 14–15, 232, 233
Li Ho, 261, 279–80
lipofuscin, 122–23, 124, 126, 132–33, 142, 173, 174; graveyard microbes and, 135–36
lithium, 195
longevity, study of. See gerontology
longevity assurance systems, 186
longevity mutants. See Methuselah mutants
Long Tomorrow, The (Rose), 184
Lucretius, 240
lungs, 75, 76, 77, 104, 204, 207
Luz, 246–47
Lyell, Charles, 161
lymphocytes, 119
lysosomes, 63, 79, 126–27, 128, 194, 277; aging and, 130–32, 133, 142–44; lipofuscin accumulation in, 133, 173; pathways by which cell carts bits of itself to, 130–31
macroautophagy, 130, 143–44
macular degeneration, 121–24, 126, 142, 172–74
Mailer, Norman, 225
Makropulos Affair, The (apek), 248–49, 252, 253–54
malaria, 104
Malthus, Thomas, 112–13
Mandeville, Sir John, 56, 70
Mannin, Ethel, 41
Mao Zedong, 261
Marlowe, Christopher, 29–31
Martínez, Daniel, 56
McCay, Clive, 66
Medawar, Peter, 64, 92–93, 94, 96–97, 101–2, 105–6, 111–12, 114, 120, 136, 184, 254, 258
medical text, first known, 25–26
meiosis, 48–49
memory, 72, 119, 125, 166, 267; origin of mortality and, 243–44
menopause, 88, 109–11
metabolism, 72, 75, 133, 144; calorie restriction and, 66–67; detritus of (see Garbage Catastrophe); three approaches to trash produced by, 124–26, 146–48, 169; TOR’s role in, 190
Metchnikoff, Elie, 39, 41
Methuselah Foundation, 275, 280
Methuselahs, 178–88; bats as, 186–87; Darwinian breeding experiments and, 182–85; disposable soma theory and, 180, 181, 183; human, engineering of, 180, 182; of molecular biologists, 178–82, 184, 188; products resulting from quest for, 188–95
mice, 187; body maintenance and short life span of, 119; calorie-restriction and, 66, 67; rapamycin tested in, 190–92; in wild, survival difficult for, 93–94, 96
Michelangelo, 52
microautophagy, 130
Middle Ages, 10
Miller, Richard, 82–83
Milton, John, 237, 241
mitochondria, 74–80, 100, 124; damaged, swallowed by autophagosomes, 79, 80–82, 143; damage to DNA in, 78, 80–81, 150, 152–57, 199; defective, multiplication of, 81–82; descended from parasites, 75–76; energy food produced by (see adenosine triphosphate); free radical damage to, 77–80; gates in, 74–75, 78; hydrophobic genes in, 154–55; migration of genes to nucleus from, 153–57; piling on of mistakes in, 79, 80
mitochondrial free radical theory (oxidative stress hypothesis), 77–82
Mitochondrial Free Radical Theory of Aging, The (de Grey), 82
molecular biology, 67, 175–85; Methuselah mutants and, 178–82, 184; skin-out vs. skin-in approach and, 175–76, 180, 181–82, 184, 185, 188, 265; technological advancements and, 129–30
molecules, cross-links and, 131–32, 133, 150–52, 157
monkey-testicle grafts, 39
Montaigne, Michel de, 223
Montgolfier brothers, 235
mortality, 223–45, 269; Buddha’s perspective on, 227; of cosmos, Galileo’s discoveries and, 225–27; history of ideas about conquest of, 28–44; human development and awareness of, 228–29, 231, 251–54; law of, 162–63; origins of, at level of single cells, 241–44; philosophers’ contemplation of, 224; poignancy of knowledge of, 230–31; pushing away thought of, 227–28, 229–30, 231; sacrifice of child by father and, 237–40; writers’ explorations of, 224, 225. See also immortality; life expectancy
mortality rates, doubling of, every eight years, 162–63
motes, 173
Mount Olympus, 27–28, 249–50
multicellular bodies, origins of, 89, 242
muscles, 72, 83; age-related changes in, 99, 100; invention of mortality and, 243–44
mutations, 150, 158; cancer problem and, 197–207; causes of, 177; DNA repair and, 118, 119; Error Catastrophe and, 177–78; impediments to keeping genomes free of, 278–79; late-onset diseases and, 98; in mitochondria, 78, 80–81, 150, 152–57; prevention of, 189; in tumors, 198
“My Intended Burial and Why” (Hamilton), 265–66
Nachiketas, 239
National Institute on Aging (NIA), 189–90, 278
National Institutes of Health (NIH), 189–90
natural philosophy, 31–32
natural selection, 94–101, 110; Darwin’s process of, 94, 97, 98, 99–100, 112, 113; late-onset diseases and, 96, 98–100, 101–2; in Weismann’s theory of mortality, 90, 92–93, 101; when individual is younger than age of reproduction, 94–98, 100, 101, 105
Nature, 189
nerve cells (neurons), 72, 124, 126, 267; accumulation of junk in, 150, 157–59, 193–95, 198; invention of mortality and, 242–44
neurodegenerative diseases, 129, 192–94, 277. See also Alzheiner’s disease; Parkinson’s disease
Neutze, Richard, 74–75
Newton, Isaac, 117, 224
New Yorker, 230, 236
New York Times, 42
1984 (Orwell), 261–62
Noah’s Ark, 71
Nobel Prize, 40, 41, 49, 92, 206
Nüsslein-Volhard, Christiane, 49
oaks, 95, 96
“Ode to a Nightingale” (Keats), 225
“Of Death” (Bacon), 248
old age, pathologies of, 124–26
“Old Age and Natural Death” (Medawar), 92–93, 136
Olshansky, S. Jay, 233
Orgel, Leslie, 177–78
original sin, 32, 261
Origin of Species, The (Darwin), 93–95, 97
Orwell, George, 261–62
Osmington Church, Dorset, England, 69
osteoclasts and osteoblasts, 83
osteopetrosis, 83
osteoporosis, 83, 88, 126, 192
“Out of the Cradle Endlessly Rocking” (Whitman), 224
oxidants. See free radicals
oxidation, cells damaged by, 77–78, 82, 256
oxidative stress hypothesis (mitochondrial free radical theory), 77–80
oxygen, 42–43, 77–78; in manufacture of ATP, 75, 76, 77; transported throughout human body, 75, 76
Paleolithic, 107–9; fossil dental records of, 107–8; survival of older adults in, 108–9
Paracelsus, 149
Paradise Lost (Milton), 237, 241
paradox of aging, 228–29
paramecia, 59–60, 89
Parkinson’s disease, 129, 157, 193, 198, 204, 277
Pascal, Blaise, 273, 275
periodontal disease, 104
periodontitis, 83
Perry, Dan, 277
Phoenix, 70, 71–72, 73, 83, 100, 246
Planck, Max, 260
Platt, Robert, 114–15
Poe, Edgar Allan, 156
political regimes, immortality and, 260–62
potions for long life, 33–34
Pratchett, Terry, 168
predators, evolution of long spans in absence of, 185–87
Priestley, Joseph, 36
Prolongation of Life, The (Metchnikoff), 39
prolongevists, 28–29
Prometheus, 27, 28
proteasomes, 143, 195
proteins: cross-linked, 131–32, 133, 150–52, 157, 163, 199; hydrophobicity and manufacture of, 157–58; misfolded, in endoplasmic reticulum, 194–95
Psalms, 12, 15, 221, 228
puberty, 88, 99, 101
Rae, Michael, 164
Raff, Martin, 254–59
Ramses the Second, 12
rapamycin, 190–93, 194, 195; Huntington’s disease and, 192–93; tested in mice, 190–92
rats, 131, 187; calorie restriction and, 66, 67
“Raven, The” (Poe), 156
Ravenna, Italy: author’s trip with de Grey to, 212–19; de Grey’s epiphany after wandering in, 200–201, 207, 211–12
recombination nodule, 48–49, 139
“Reflections on Aging and Death” (Platt), 114–15
Rejuvenation Research, 216, 255
Rejuvenation through the Experimental Revitalization of the Aging Puberty Gland (Steinach), 40
Renaissance, 10, 29–35, 223
Renard, Jules, 113
reproduction: balance between investing in body’s own maintenance and, 118–19; by budding, 244; at later ages, longer life spans and, 183, 185–86, 187–88. See also natural selection
respiratory problems, 104
restoration process, 72–74. See also creation-destruction balance
resveratrol, 189, 273, 275
retinas: derived from brain cells, 174; macular degeneration and, 121–24, 126, 142, 172–74
retirement, 61, 97, 98, 106, 254, 259
rheumatoid arthritis, 83
Rhodococcus, 137–38
Riddle of the Universe (Haeckel), 248
Rittmann, Bruce, 141
Rockefeller Institute for Medical Research, New York, 39, 41, 57, 61–62, 63, 67, 182, 266
Roman Empire, 10
Rose, Michael, 182–85
Roth, Eric, 268, 270, 271
Royal Air Force (RAF), 4, 6, 181, 230–31
Royle, Nicola, 205
rubber, eaten by soil microbes, 134
Rubinsztein, David C., 193, 195
Ruddock, Margot, 41
Rudzinska, Maria, 57–68, 129, 182
Ruvkun, Gary, 185
sarcopenia, 99, 100
Science, 154
Scientific American Monthly, 40
scientific discoveries, acceptance of, 117, 260
“Self-Portrait” (Capote), 249
Seneca, 224, 248
SENS Foundation, 280
seven ages of man: immortality and, 251–54; Shakespeare’s speech on, 52–53, 54, 97–98