Sarkar, S., B. Ravikumar, et al. (2009). “Autophagic clearance of aggregate-prone proteins associated with neurodegeneration.” Methods Enzymol 453: 83–110.
CHAPTER 9: THE WEAKEST LINK
Aubrey de Grey introduced his cancer cure in these papers:
de Grey, A. D. (2005). “Whole-body interdiction of lengthening of telomeres: a proposal for cancer prevention.” Front Biosci 10: 2420–29.
de Grey, A. D., F. C. Campbell, et al. (2004). “Total deletion of in vivo telomere elongation capacity: an ambitious but possibly ultimate cure for all age-related human cancers.” Ann N Y Acad Sci 1019: 147–70.
De Grey writes about his hopes for the Singularity in Edge.com, January 2, 2009. http://ieet.org/index.php/IEEET/more/2781.
See also de Grey, A. D. (2009). “The singularity and the Methuselarity: Similarities and differences.” Stud Health Technol Inform 149: 195–202. Here he writes, “Aging, being a composite of innumerable types of molecular and cellular decay, will be defeated incrementally. I have for some time predicted that this succession of advances will feature a threshold, which I here christen the ‘Methuselarity….’” As he says, that threshold is very close to the Singularity.
For a massive defense of the Singularity idea, see Kurzweil, R. (2005). The Singularity Is Near: When Humans Transcend Biology. Viking.
CHAPTER 10: LONG FOR THIS WORLD
For an excellent collection of papers on aspects of the great questions “can we” and “should we,” see:
Post, S. G., and R. H. Binstock, eds. (2004). The Fountain of Youth: Cultural, Scientific, and Ethical Perspectives on a Biomedical Goal. Oxford University Press.
For John Cheever’s envy of Saul Bellow’s immortality, see Atlas, J. (2000). Bellow: A Biography. Random House.
Updike’s last book of poems is one of his finest: Endpoint and Other Poems (2009). Alfred A. Knopf.
Because life expectancy has lengthened within the lifetimes of baby boomers, they may find the approach of old age even more disturbing, in some ways, than generations past. What if their ship is sinking within sight of land? Shakespeare speaks of the “double death”: “’Tis double death to drown in ken of shore.”
For an insightful essay on baby boomers’ competition for more years, see Kinsley, M. (2008). “Mine is longer than yours.” New Yorker (April 7).
On the psychology of time—our own private expectations of how much or little time lies ahead—see Carstensen, L. L. (2006). “The influence of a sense of time on human development.” Science 312(5782): 1913–15.
There is a large and growing literature on twenty-first-century demography. In this chapter, I cite Christensen, K., G. Doblhammer, et al. (2009). “Ageing populations: the challenges ahead.” Lancet 374(9696): 1196–208. Christensen, K., A. M. Herskind, et al. (2006). “Why Danes are smug: comparative study of life satisfaction in the European Union.” Bmj 333(7582): 1289–91.
For Aubrey de Grey’s rejection of demographers’ forecasts:
de Grey, A. D. (2006). “Extrapolaholics anonymous: Why demographers’ rejections of a huge rise in cohort life expectancy in this century are overconfident.” Ann N Y Acad Sci 1067: 83–93.
Terman, A., and U. T. Brunk (2005). “Is aging the price for memory?” Biogerontology 6:205–10.
CHAPTER 11: THE TROUBLE WITH IMMORTALITY
For the story of Luz, I consulted The Book of Legends, Bialik and Braude (op cit.).
This book is still worth reading, although it is dated by its conviction that Freud and his disciples had us figured out: Becker, E. (1973). The Denial of Death. Free Press.
For a wonderful new book exploring some of the same emotional territory, read Barnes, J. (2008). Nothing to Be Frightened Of. Alfred A. Knopf.
Veatch, R. M. (2009). “The evolution of death and dying controversies.” Hastings Center Report 39(3): 16–19.
Haeckel, E. (1900). The Riddle of the Universe. Harper & Brothers.
apek, K. (1925). The Makropulos Secret. International Pocket Library.
Bernard Williams’s paper about apek’s play is reprinted here:
Williams, B. (1973). Problems of the Self. Cambridge University Press.
Someday soon, neurophilosophers may be able to explore Joshua Lederberg’s point about remembering and forgetting. See, for instance:
Shuai, Y., B. Lu, et al. (2010). “Forgetting is regulated through Rac activity in Drosophila.” Cell 140(4): 579–89.
And see Bhanoo, S. N. (2010). “Forgetting, with a purpose.” New York Times.
If we ever do stop aging, what will become of the wisdom of the ages? Everything ever written about childhood, youth, middle and old age will seem incredibly dated. For the time being, at least, this is still a valuable anthology:
Sampson, A., and S. Sampson (1985). The Oxford Book of Ages. Oxford University Press.
CHAPTER 12: THE EVERLASTING YES AND NO
Robert Butler writes about the “longevity dividend” in his book The Longevity Revolution (op cit.). See also Butler, R. N., R. A. Miller, et al. (2008). “New model of health promotion and disease prevention for the 21st century.” BMJ 337: a399.
Two attacks from the center against the fringes of antiaging medicine:
Olshansky, S. J., L. Hayflick, et al. (2002). “Position statement on human aging.” J Gerontol A Biol Sci Med Sci 57(8): B292–97.
Olshansky, S. J., L. Hayflick, et al. (2002). “No truth to the fountain of youth.” Sci Am 286(6): 92–95.
Vijg, J. (2007). Aging of the Genome: The Dual Role of DNA in Life and Death. Oxford University Press.
Houellebecq, M. (2001). The Elementary Particles. New York, Vintage.
Graham, A. C., trans. (2008). Poems of the Late T’ang. NYRB Classics.
William Butler Yeats composed beautiful translations of the Upanishads. Yeats, W. B., and Swami Shree, trans. (1975). The Ten Principal Upanishads. Macmillan.
Searchable Terms
The pagination of this electronic edition does not match the edition from which it was created. To locate a specific passage, please use the search feature of your e-book reader.
Abraham, 237–40
accidents, 276; fatal, 37, 93–94, 114, 165; re-creating patient in case of, 166–67
Adam and Eve, 13, 27, 32, 33, 71, 78, 237, 239
adenosine triphosphate (ATP), 97, 195; apertures in mitochondrial membrane for ingredients of, 74–75, 78; free radicals and, 77; manufacture of, 74–77; mutant mitochondria and, 80–81; tearing apart and rebuilding of, 79–80
advanced glycation endproducts (AGEs), 132, 133, 150–52
Advancement of Learning, The (Bacon), 33, 85
Advances in Anti-Aging Medicine (Klatz), 120
Agamemnon, 238, 240
Age, 82
age-1 gene, 179
aging, 14, 15; as adaptation, 89–91, 92–93, 102, 109, 111–12, 113; causes of, rooted in early life, 162, 163; considered impossible to treat or cure, 48, 49–50, 54; as disease, 115; disorderliness of, 50–54, 115–16, 146; evolutionary theory of, 83–84, 87–116, 117, 146, 178, 182–84, 185–88, 196, 242–44; getting older without, 113–14; at level of single cells, 241–43; of living vs. man-made things, 65; as maintenance failure, 118–74 (see also Garbage Catastrophe); mitochondrial free radical theory of (oxidative stress hypothesis), 77–82; not visible until we are thirty or forty, 163; plethora of theories of, 64; regularities in, 52–53
Aging and the Genome (Vijg), 278–79
“Aging Is No Longer an Unsolved Problem in Biology” (Holliday), 117–18
Allen, Woody, 249
Alteon, 151–52
Alzheimer’s disease, 77, 103, 129, 142, 157–59, 173–74, 198, 204
American Academy of Anti-Aging Medicine, 264
American Aging Association (AGE), 82
amoebae, 59–60, 89, 91
amyotrophic lateral sclerosis (ALS), 193
anabolism, 72, 190
Annals of the New York Academy of Sciences, 18–19
“Anthem”
(Cohen), 256
antioxidants, 82, 273–74
antiwrinkle cream, 25–26, 131, 151
Antony and Cleopatra (Shakespeare), 260
ants, dead, disposal of, 81
ape-testicle transplants, 40
aphids, shifts of genes between bacteria and, 153–54
apologists, 28, 29, 31
apoptosis, 255, 257
Archer, John, 133–34, 135–39, 141
Aristotle, 112, 121
arthritis, 77, 83
asthma, 105
astronomy, mortality of cosmos and, 225–27
As You Like It (Shakespeare), 52–53, 54, 94, 97–98
atherosclerosis, 163
ATP. See adenosine triphosphate
A2E, 122–23
Aubrey, John, 35
Auden, W. H., 255
Auerback, Erich, 253
autophagosomes, 79, 80–82, 100, 195. See also lysosomes
autophagy, 63, 79, 130, 143, 190, 192, 194, 195; macroautophagy, 130, 143–44
Bacon, Francis, 25, 31–38, 43, 50, 58, 65, 76, 85, 88, 114, 152, 161–62, 163, 248, 269
Bacon, Roger, 25, 32, 149
bacteria, 138; in gut, 39, 153–54; parasitic, mitochondria as descendants of, 75–76. See also soil microbes
bats, as Methuselahs, 186–87
Becker, Ernest, 251
Bellow, Saul, 225
Benzer, Seymour, 156–57, 181, 190
beta-amyloid protein (BAP), 142, 158, 159, 160, 173–74
Beyond the Pleasure Principle (Freud), 92
Bible, 15, 263–64; Abraham’s sacrifice of Isaac in, 237–40; King James version of, 12–13, 31. See also Adam and Eve
bifocals, 43
bioethical issues, 264–65
bioremediation (environmental biotechnology), 133–36, 137–39; graveyard microbes and, 134–36, 138–39, 141
birthrates, longevity increases and, 164–65, 213, 240
Black Elk, 224
blindness, 126
blood, 73, 206
bone marrow, 204, 243
Borden, Gavin, 257, 258
boredom, immortality and, 247–51
brain, 72, 119, 143, 166, 243; beta amyloid in, 142, 158; consciousness and, 14, 158–59; human, large size of, 106, 110–11; junk accumulated in cells of, 150, 157–59, 193–95, 198; vision and, 121, 122. See also nerve cells
Brief Lives (Aubrey), 35
Brown-Séquard, Charles-Édouard, 39–40, 41, 42
Brunk, Ulf T., 135, 144, 243
Buddha, 227
budding, reproduction by, 244
Burghley, David George, 46
Burns, Robert, 262
Butler, Robert, 276–77
Caenorhabditis elegans, 49; Methuselah mutants, 178–80
Calment, Jeanne, 13
calorie restriction, 66–67, 83, 179, 187–89; adaptive responses during famine and, 192; genes and their products involved in, 188–89, 192
Calvary (Golgotha), 238–39
Cambrian Explosion, 244
Cambridge University, 46, 82
Campisi, Judith, 19–20
cancer, 77, 103, 104, 129, 177, 192, 197–207, 255, 257; caused by mutations in DNA, 197–98; evolution and growth of tumors in, 198, 202; telomerase elimination and (WILT procedure), 202–7
apek, Karel, 248–49, 252, 253–54
Capote, Truman, 249
carbamazepine, 195
Carlyle, Thomas, 271
Carpenter, Adelaide, 17, 47–49, 136, 139–40, 172, 224, 271–72, 275–76, 282
Carrel, Alexis, 41–43, 57, 61
Carstensen, Laura L., 228–29
Caspari, Rachel, 107–9
catabolism, 72, 190
cataracts, 123
cell division, 129; in cancer, 202; in Carrel’s petri dish of human cells, 42–43; human cells that do not undergo, 124; inequality in, 241; in single-celled organisms, 91; slight errors in, 162 (see also mutations); telomeres and, 201
cell membranes, beta-amyloid and, 142
cells, 100; amount of DNA in, 177–78; ATP manufacture in, 74–77; dead, surrounding cells poisoned by, 150, 199; garbage-disposal system in, 63, 79, 126–32, 198 (see also lysosomes); junk in spaces between, 150, 198; migration of genes from mitochondria to nucleus of, 153–57; old and useless, hanging around in body, 150, 199; origins of aging at level of, 241–44; oxidative damage to, 77–78, 82, 256; suicide of (apoptosis), 255, 257. See also human cells; single-celled animals
centenarians, 232–33
Chaderton, Laurence, 13
chaos, in aging process, 51–54, 115–16, 146
chaperones, 130, 132
Charlesworth, Brian, 183
Cheever, John, 225
Chekhov, Anton, 234
chemotherapy, in WILT procedure, 204, 205
childbearing, 111, 116; brain size and, 110; longevity increases and, 164–65, 213, 240
childhood, 103–5, 114; awareness of mortality in, 227; damage leading to aging present in, 162, 163; grandparents’ help in, 106–11; infections in, 103–5; mortality in, 10, 12, 18, 103
China, ancient, 28–29; Emperor Wu in, 260–61; immortal lines of poetry from, 279–80
Christensen, Kaare, 232
chromosomes: telomeres at tips of, 201, 203, 205. See also DNA; genes
Clytemnestra, 238
cnidarians, 242. See also hydras
Cohen, Leonard, 256
collagen, 131, 150–52
Comfort, Alex, 64
computer science, 46–47, 140
Condorcet, Marquis de, 37, 113
consciousness, 14, 158–59, 244–45
C-reactive protein (CRP), 104
creation-destruction balance, 72–74, 79–80, 83–84, 118, 132, 142–43; famine and, 192; housekeeping genes and, 128–29; in women between puberty and menopause, 88–89
creative explosion, in Upper Paleolithic, 109
Crick, Francis, 4, 48, 76–77, 117, 140, 176, 177, 180, 231
cross-links, 131–32, 133, 150–52, 157, 163, 199
Cuervo, Ana Maria, 126–32, 277
culture, human, 106–7, 109
Cure-All, 47, 140
cytosol, 195
dandelions, 96, 97
Dante, 201, 212, 215, 216, 217, 253
Darwin, Charles, 89, 102, 117, 161, 176, 186, 224; natural selection and, 94, 97, 98, 99–100, 112, 113; struggle for existence and, 93–97
David, King, 12, 246–47
Dawkins, Richard, 113
death: as adaptation, 89–91, 92–93, 96, 111–12, 113; of cells, apoptosis, 255; contemplation of, 224; difficulty of defining moment of, 136; euthanasia and, 257–58, 259; fear of dying vs., 258; struggle for existence in wild and, 93–95.
See also mortality
de Duve, Christian, 63
de Grey, Aubrey, 5–9, 15–22, 24, 45–49, 80–83, 145–74, 182, 196, 197–219, 224–25, 254, 255, 260, 271–72, 275–76, 278, 279, 280–82; author’s trip to Forlì and Ravenna with, 209–19; on boredom issue, 247–48; cancer problem and, 197–207; cleanup projects envisioned by, 17–18, 124–26, 127–28, 132–41, 145–74, 194, 197–99 (see also Seven Deadly Things); as computer scientist, 46–47, 140, 170; gerontologists disdained by, 170–71, 207–9; graveyard microbes and, 134–36, 138–39, 141; personality and demeanor of, 15–16, 20–22, 24, 45–46, 148–49, 171–72; on re-creating patient in case of accidents, 166–67; as theoretical biologist, 139, 169–70; theory of aging hypothesized by, 80–82; WILT procedure and, 203–7
de la Mare, Walter, 125
dementias, 158–59. See also Alzheimer’s disease
Demeny, Paul, 213
demographers, 208, 213, 234, 240
Denial of Death, The (Becker), 251
Denmark, longevity improvements in, 232–33
Descartes, René, 36, 273, 275
destruction and restoration process, 72–74
detoxification, 127
developmental biology, 48–49, 50–51
diabetes, 142, 192, 204
diarrhea, 104
dicarbonyl linkages, 151
digestion, 125
Dillard, Annie, 224
disposable soma theory, 102–24, 147, 277–78; aging and death as accidental outcomes in, 111–16; aging viewed as slow failure of maintenance in, 118–21 (see also Garbage Catastrophe); childhood infections and, 103–5; grandparents’ survival and, 106–11; Medawar’s insight leading to, 96–97, 101–2; Methuselahs and, 180, 181, 183; vision problems and, 121–24
Divine Comedy (Dante), 201, 212, 215, 217
DNA, 76, 97; amount in, in each cell, 177–78; free radical damage to, 77, 78, 118; mitochondrial, damage to, 78, 80–81, 150, 152–57, 199; piling up of errors in (see Error Catastrophe); proofreading of, 197–98; repair of, 118, 119, 189, 197; Watson and Crick’s breakthrough on, 4, 48, 117, 140, 231. See also genes; mutations
Doctor Faustus (Marlowe), 29–31
Donne, John, 76
Double Helix, The (Watson), 4, 231
drugs that slow aging in mammals, 189–93
drusen, 123–24
Eagle, Cambridge, England, 3–9, 20–22, 24, 117, 140–41, 281–82; DNA Room at, 4, 231; history of, 3–4, 10–11; RAF Room at, 4, 230–31
Earth: evolution of life on, 87–88; human immortality and health of, 263
egg. See germ cells
Egypt, ancient, 12, 25–26, 71, 131
elastosis, 151
Elementary Particles, The (Houellebecq), 279
elephants, 95, 96, 97
embryonic development, 48–49, 50–51, 102, 116, 143, 162
Ending Aging (de Grey), 164, 200, 275
endoplasmic reticulum, 194–95
endoplasmic reticulum–associated degradation (ERAD), 195
Endpoint (Updike), 225
energy, 100; aging of mitochondria and, 152, 199; calorie restriction and, 188; expended on maintenance vs. reproduction, 118–19; struggle for existence and, 96–97. See also adenosine triphosphate
Enlightenment, 35–38, 44, 240
enteritis, infant, 104
entropy, law of, 87
environmental biotechnology. See bioremediation
Eos, 27
Error Catastrophe, 177–78, 189
escape velocity, de Grey’s notion of, 164, 208, 218, 280