Long For This World_ The Strange Science Of Immortality Part 10

Aubrey de Grey has published a book about his "Strategies for Negligible Senescence": de Grey, A. D. N. J., with Michael Rae (2007). Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. St. Martin's.

Aubrey de Grey has also published almost one hundred manifestos and scientific articles on the subject. For one of the early, provocative papers in which he rode out to battle against most gerontologists, see de Grey, A. D., B. N. Ames, et al. (2002). "Time to talk SENS: Critiquing the immutability of human aging." Ann N Y Acad Sci Ann N Y Acad Sci 959: 45262; discussion 46365. As de Grey and his coauthors write, "Aging is a three-stage process: metabolism, damage, and pathology. The biochemical processes that sustain life generate toxins as an intrinsic side effect. These toxins cause damage, of which a small proportion cannot be removed by any endogenous repair process and thus acc.u.mulates." Finding ways to remove the acc.u.mulating damage, they argue, "would sever the link between metabolism and pathology, and so has the potential to postpone aging indefinitely.... Such ways exist in all cases, implying that indefinite postponement of aging-which we term 'engineered negligible senescence'-may be within sight." 959: 45262; discussion 46365. As de Grey and his coauthors write, "Aging is a three-stage process: metabolism, damage, and pathology. The biochemical processes that sustain life generate toxins as an intrinsic side effect. These toxins cause damage, of which a small proportion cannot be removed by any endogenous repair process and thus acc.u.mulates." Finding ways to remove the acc.u.mulating damage, they argue, "would sever the link between metabolism and pathology, and so has the potential to postpone aging indefinitely.... Such ways exist in all cases, implying that indefinite postponement of aging-which we term 'engineered negligible senescence'-may be within sight."

See also: de Grey, A. D., J. W. Baynes, et al. (2002). "Is human aging still mysterious enough to be left only to scientists?" Bioessays Bioessays 24(7): 66776. 24(7): 66776.

de Grey, A. D. (2003). "An engineer's approach to the development of real anti-aging medicine." Sci Aging Knowledge Environ Sci Aging Knowledge Environ 2003(1): VP1. 2003(1): VP1.

de Grey, A. D. (2004). "Biogerontologists' duty to discuss timescales publicly." Ann N Y Acad Sci Ann N Y Acad Sci 1019: 54245. 1019: 54245.

de Grey, A. D. "Resistance to debate on how to postpone ageing is delaying progress and costing lives." EMBO Rep EMBO Rep 2005; 6:S49S53. 2005; 6:S49S53.

For an angry counterattack by gerontologists, see: Warner, H., J. Anderson, et al. (2005). "Science fact and the SENS agenda: What can we reasonably expect from ageing research?" EMBO Rep EMBO Rep: 26:10068.

For de Grey's defense, see these papers, and their references: de Grey, A. D. (2006). "Is SENS a farrago?" Rejuvenation Res Rejuvenation Res 9(4): 43639; de Grey, A. D. (2006). "SENS survives the challenge: Now let's get to work." 9(4): 43639; de Grey, A. D. (2006). "SENS survives the challenge: Now let's get to work." Rejuvenation Res Rejuvenation Res 9(4): 42930. 9(4): 42930.

Among dozens of recent technical reviews of current gerontology, I found this one particularly useful as a balanced guide to the literature: Vijg, J., and J. Campisi (2008). "Puzzles, promises and a cure for ageing." Nature Nature 454(7208): 106571. Vijg and Campisi survey recent discoveries in the science of aging, which seem to show that the life span of yeast, worms, flies, and mice "is plastic and can be manipulated." The authors caution that we need to understand those studies much more deeply "before we can evaluate if abrogation of human senescence is a realistic prospect." 454(7208): 106571. Vijg and Campisi survey recent discoveries in the science of aging, which seem to show that the life span of yeast, worms, flies, and mice "is plastic and can be manipulated." The authors caution that we need to understand those studies much more deeply "before we can evaluate if abrogation of human senescence is a realistic prospect."

On the history of human longevity, I found these books helpful, among others: Riley, J. C. (2001). Rising Life Expectancy: A Global History. Rising Life Expectancy: A Global History. Cambridge University Press. Cambridge University Press.

Anderson, M. (1996). British Population History British Population History. Cambridge University Press.

The owners of the Eagle are justly proud of its history, and there are many plaques in the pub. John Chainey's notes on the RAF graffiti are detailed and extensive.

I also consulted a few books about the town's history, including: Darby, H. C. (1977). Medieval Cambridgeshire Medieval Cambridgeshire. Oleander.

Cobban, A. B. (1988). The Medieval English Universities: Oxford and Cambridge to circa 1500 The Medieval English Universities: Oxford and Cambridge to circa 1500. Scholar.

Blair, J. (1984). The Anglo-Saxon Age: A Very Short Introduction The Anglo-Saxon Age: A Very Short Introduction. Oxford University Press.

CHAPTER 2: THE PROBLEM OF MORTALITY.

These are two good panoramic surveys of the subject's history: Gruman, G. J. (1966). A History of Ideas About the Prolongation of Life A History of Ideas About the Prolongation of Life. Springer.

Hanc.o.c.k, D. B. (2009). Mortal Coil: A Short History of Living Longer Mortal Coil: A Short History of Living Longer. Yale University Press.

For a wise short review, read: Shapin, S., and C. Martyn (2000). "How to live forever: Lessons of history." BMJ BMJ 321: 158082. 321: 158082.

An excellent book about Gilgamesh: Damrosch, D. (2007). The Buried Book: The Loss and Rediscovery of the Great Epic of Gilgamesh The Buried Book: The Loss and Rediscovery of the Great Epic of Gilgamesh. Holt.

On Steinach: Wyndham, D. (2003). "Versemaking and lovemaking-W. B. Yeats' 'Strange Second p.u.b.erty': Norman Haire and the Steinach rejuvenation operation." Journal of History of the Behavioral Sciences Journal of History of the Behavioral Sciences 39(1): 2550. 39(1): 2550.

I've mentioned only a few twentieth-century immortalists in this chapter. If you dig down into any decade, you can find a dozen now forgotten doctors and biologists who hoped to live forever. A few months ago I found an old, slightly pulpy, but entertaining paperback: McGrady, P. M., Jr. (1968). The Youth Doctors The Youth Doctors. Ace. It is full of names of lost immortalists, including one rebel whose polemics have at least a family resemblance to Aubrey de Grey's.

See also Comfort, A. The Process of Ageing The Process of Ageing (1964). Signet Science Library. Dated, but still good reading. (1964). Signet Science Library. Dated, but still good reading.

Another readable paperback from that time, also with yellowing pages: Harrington, A. (1969). The Immortalist: An Approach to the Engineering of Man's Divinity The Immortalist: An Approach to the Engineering of Man's Divinity. Avon. It begins, "Death is an imposition on the human race, and no longer acceptable."

CHAPTER 3: LIFE AND DEATH OF A CELL.

Here are a few books about the beauty of the beginning of the life cycle: Bonner, J. T. (1993). Life Cycles: Reflections of an Evolutionary Biologist Life Cycles: Reflections of an Evolutionary Biologist. Princeton University Press. John Tyler Bonner, born in 1920 and still going strong, is one of the best biologist-writers alive. This is a delightful book about the evolution of the life cycle, and the evolution of Bonner.

Gilbert, S. F. (2006). Developmental Biology Developmental Biology. Sinauer. The standard textbook.

Wolpert, L. (1991). The Triumph of the Embryo The Triumph of the Embryo. Oxford University Press.

On the evolution of multicellular life: Bonner, J. T. (2000). First Signals: The Evolution of Multicellular Development First Signals: The Evolution of Multicellular Development. Princeton University Press.

Buss, L. W. (1987). The Evolution of Individuality The Evolution of Individuality. Princeton University Press. A bit old, and difficult, but fascinating.

This monumental work of scholarship helped bring new life to the science of gerontology: Finch, C. E. (1990). Longevity, Senescence, and the Genome Longevity, Senescence, and the Genome. University of Chicago Press.

On the hydra: Martinez, D. E. (1998). "Mortality patterns suggest lack of senescence in hydra." Exp Gerontol Exp Gerontol 33: 21725. 33: 21725.

Maria Rudzinska was working in a long tradition at Rockefeller University. Not only was Alex Carrel there before her, so was another early eminence there, Jacques Loeb. See, for instance: Loeb, J., and J. H. Northrup (1917). "On the influence of food and temperature upon the duration of life." Biological Chem Biological Chem. 32: 10321.

Two of Rudzinska's papers on her beloved Tokophrya Tokophrya: Rudzinska, M. A. (1951). "The influence of amount of food on the reproduction rate and longevity of a suctorian (Tokophrya infusionum)." Science Science 113: 1011. 113: 1011.

Rudzinska, M. A. (1984). "Cellular and clonal aging in the suctorian protozoan Tokophrya infusionum." S. J. Karakashian, H. N. Lanners, and M. A. Rudzinska. Mech. Ageing Develop. Mech. Ageing Develop. 26: 21729. 26: 21729.

CHAPTER 4: INTO THE NEST OF THE PHOENIX.

A wonderful and authoritative collection of old Jewish legends: The Book of Legends, Sefer Ha-Aggadah: Legends from the Talmud and Midrash The Book of Legends, Sefer Ha-Aggadah: Legends from the Talmud and Midrash (1999). H. N. Bialik, editor; W. Braude, translator. Schocken. (1999). H. N. Bialik, editor; W. Braude, translator. Schocken.

For reviews of Denham Harman's thinking about aging, see: Harman, D. (2006). "Free radical theory of aging: an update," Ann NY Acad Sci Ann NY Acad Sci 1067: 1021. 1067: 1021.

Kitani, K., and G. O. Ivy (2003). "'I thought, thought, thought for four months in vain and suddenly the idea came.' Interview with Denham and Helen Harman." Biogerontology Biogerontology 4: 40112. 4: 40112.

de Grey, A. D. (1997). "A proposed refinement of the mitochondrial free radical theory of aging." Bioessays Bioessays 19(2): 16166. 19(2): 16166.

de Grey, A. D. (2002). "Three detailed hypotheses implicating oxidative damage to mitochondria as a major driving force in homeotherm aging." Eur J Biochem Eur J Biochem 269(8): 1995. 269(8): 1995.

CHAPTER 5: THE EVOLUTION OF AGING.

Peter Medawar's key essays about the evolution of aging are reprinted in: Medawar, P. (1981). The Uniqueness of the Individual The Uniqueness of the Individual. Dover.

He returns to the subject in his quirky autobiography: Medawar, P. (1988). Memoir of a Thinking Radish Memoir of a Thinking Radish. Oxford University Press.

And again in: Medawar, P. (1990). The Threat and the Glory The Threat and the Glory. HarperCollins.

See also: Finch, C. E., and E. M. Crimmins (2004). "Inflammatory exposure and historical changes in human life-spans." Science Science 305(5691): 173639. 305(5691): 173639.

Caspari, R., and Lee, S.-H. (2004). "Older age becomes common late in human evolution." PNAS PNAS 101(30): 1089510900. 101(30): 1089510900.

Crespi, B. J. (2004). "Vicious circles: Positive feedback in major evolutionary and ecological transitions." TREE TREE 19(12): 62733. 19(12): 62733.

Rose, M. R. (1991). Evolutionary Biology of Aging Evolutionary Biology of Aging. Oxford University Press.

Stearns, S. C., and J. C. Koella (2008). Evolution in Health and Disease Evolution in Health and Disease. Oxford University Press.

Platt, R. (1963). "Reflections on ageing and death." Lancet Lancet. 281: 16.

CHAPTER 6: THE GARBAGE CATASTROPHE.

Holliday, R. (2006). "Aging is no longer an unsolved problem in biology." Ann NY Acad Sci Ann NY Acad Sci 1067: 19. 1067: 19.

de Grey, A. D. (2007). "Alzheimer's, atherosclerosis, and aggregates: A role for bacterial degradation." Nutr Rev Nutr Rev 65(12 Pt 2): S22127. 65(12 Pt 2): S22127.

Terman, A., and U. T. Brunk (2006). "Oxidative stress, acc.u.mulation of biological 'garbage,' and aging." Antioxid Redox Signal Antioxid Redox Signal 8(12): 197204. 8(12): 197204.

Stroikin, Y., H. Dalen, et al. (2005). "Testing the 'garbage' acc.u.mulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy." Biogerontology Biogerontology 6(1): 3947. 6(1): 3947.

CHAPTER 7: THE SEVEN DEADLY THINGS.

For a full-length treatment of de Grey's Strategies for the Engineering of Negligible Senescence, see his book Ending Aging Ending Aging (op cit.). (op cit.).

He's also published dozens of shorter accounts, including: de Grey, A. D. (2005). "A strategy for postponing aging indefinitely." Stud Health Technol Inform Stud Health Technol Inform 118: 20919. 118: 20919.

For Michael Hecht's experiments with beta-amyloid: Kim, W., Y. Kim, et al. (2006). "A high-throughput screen for compounds that inhibit aggregation of the Alzheimer's peptide." ACS Chem Biol ACS Chem Biol 1(7): 46169. 1(7): 46169.

Kim, W., and M. H. Hecht (2008). "Mutations enhance the aggregation propensity of the Alzheimer's A beta peptide." J Mol Biol J Mol Biol 377(2): 56574. 377(2): 56574.

de Grey, A. D., P. J. Alvarez, et al. (2005). "Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases." Ageing Res Rev Ageing Res Rev 4(3): 31538. 4(3): 31538.

CHAPTER 8: THE METHUSELAH WARS.

For a meticulously detailed contemporary history, see Hall, S. (2003). Merchants of Immortality: Chasing the Dream of Human Life Extension Merchants of Immortality: Chasing the Dream of Human Life Extension. Houghton Mifflin.

Kla.s.s, M. R. (1983). "A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results." Mech Ageing Dev Mech Ageing Dev 22(34): 27986. 22(34): 27986.

Kla.s.s, M., and D. Hirsh (1976). "Non-ageing developmental variant of Caenorhabditis elegans." Nature Nature 260(5551): 52325. 260(5551): 52325.

Kenyon, C., J. Chang, et al. (1993). "A C. elegans mutant that lives twice as long as wild type." Nature Nature 366(6454): 46164. 366(6454): 46164.

Kenyon, C. (2005). "The Plasticity of Aging: Insights from Long-Lived Mutants." Cell Cell 120: 44960. 120: 44960.

Song, S., and T. Finkel (2007). "GAPDH and the search for alternative energy." Nature Cell Biology Nature Cell Biology 9(8): 86970. 9(8): 86970.

Zhang C., and A. M. Cuervo (2008). "Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function." Nat Med Nat Med 14(9): 95965. 14(9): 95965.

Kaushik S., and A. M. Cuervo (2008). "Chaperone-mediated autophagy." Methods Mol Biol Methods Mol Biol 445:22744. 445:22744.

Cuervo, A. M. (2008). "Autophagy and aging: Keeping that old broom working." Trends Genet Trends Genet 24: 60412. 24: 60412.

Cuervo, A. M., L. Stefanis, et al. (2004). "Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy." Science Science 305: 129295. 305: 129295.

Mizushima N., B. Levine, et al. (2008). "Autophagy fights disease through cellular self-digestion." Nature Nature 451:106975. 451:106975.

Hansen, M., A. Chandra, et al. (2008). "A role for autophagy in the extension of lifespan by dietary restriction in C. elegans." PLoS Genet PLoS Genet 4(2): e24. 4(2): e24.

Rubinsztein, D. C., J. E. Gestwicki, et al. (2007). "Potential therapeutic applications of autophagy." Nat Rev Drug Discov Nat Rev Drug Discov 6(4): 30412. 6(4): 30412.

Sarkar, S., E. O. Perlstein, et al. (2007). "Small molecules enhance autophagy and reduce toxicity in Huntington's disease models." Nat Chem Biol Nat Chem Biol 3(6): 33138. 3(6): 33138.

Sarkar, S., B. Ravik.u.mar, et al. (2009). "Autophagic clearance of aggregate-p.r.o.ne proteins a.s.sociated with neurodegeneration." Methods Enzymol Methods Enzymol 453: 83110. 453: 83110.