by Bill Gifford
5. “their brains had all the hallmarks of clinical Alzheimer’s”: I. Driscoll, S. M. Resnick, J. C. Troncoso, Y. An, R. O’Brien, and A. B. Zonderman, “Impact of Alzheimer’s Pathology on Cognitive Trajectories in Nondemented Elderly,” Annals of Neurology 60, no. 6 (Dec 2006): 688-95.
6. “what’s called cognitive reserve”: Good summary of the topic in Yaakov Stern, “Cognitive Reserve,” Neuropsychologia 47, no. 10 (August 2009): 2015-28.
7. “Jet lag ages you.”: A. J. Davidson, M. T. Sellix, J. Daniel, S. Yamazaki, M. Menaker, and G. D. Block, “Chronic Jet-Lag Increases Mortality in Aged Mice,” Current Biology 16, no. 21 (November 7, 2006): R914-6.
8. “half of all Alzheimer’s cases could actually be prevented”: D. E. Barnes, and K. Yaffe, “The Projected Effect of Risk Factor Reduction on Alzheimer’s Disease Prevalence,” Lancet Neurology 10, no. 9 (September 2011): 819-28.
9. “merely walking twenty minutes a day”: J. Winchester, M. B. Dick, D. Gillen, B. Reed, B. Miller, J. Tinklenberg, D. Mungas, et al., “Walking Stabilizes Cognitive Functioning in Alzheimer’s Disease across One Year,” Archives of Gerontololgy and Geriatrics 56, no. 1 (January–February 2013): 96-103.
10. “Old blood hurts your brain”: S. A. Villeda, J. Luo, K. I. Mosher, B. Zou, M. Britschgi, G. Bieri, T. M. Stan, et al., “The Ageing Systemic Milieu Negatively Regulates Neurogenesis and Cognitive Function,” Nature 477, no. 7362 (September 1, 2011): 90-4.
11. “Young blood had restored their old brains.”: S. A. Villeda, K. E. Plambeck, J. Middeldorp, J. M. Castellano, K. I. Mosher, J. Luo, L. K. Smith, et al., “Young Blood Reverses Age-Related Impairments in Cognitive Function and Synaptic Plasticity in Mice,” Nature Medicine 20, no. 6 (June 2014): 659-63.
12. “to repair their injured muscles.”: I. M. Conboy, M. J. Conboy, A. J. Wagers, E. R. Girma, I. L. Weissman, and T. A. Rando, “Rejuvenation of Aged Progenitor Cells by Exposure to a Young Systemic Environment.” Nature 433, no. 7027 (February 17, 2005): 760-4.
13. “It had set back the clock”: F. S. Loffredo, M. L. Steinhauser, S. M. Jay, J. Gannon, J. R. Pancoast, P. Yalamanchi, M. Sinha, et al., “Growth Differentiation Factor 11 Is a Circulating Factor That Reverses Age-Related Cardiac Hypertrophy,” Cell 153, no. 4 (May 9 2013): 828-39. The story is also told in “Young Blood,” Science, September 12, 2014: Vol. 345 no. 6202 pp. 1234-1237.
14. “The elderly mice had even regained their sense of smell”: L. Katsimpardi, N. K. Litterman, P. A. Schein, C. M. Miller, F. S. Loffredo, G. R. Wojtkiewicz, J. W. Chen, et al., “Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors.” Science 344, no. 6184 (May 9, 2014): 630-4. The muscle-rejuvenation paper is M. Sinha, Y. C. Jang, J. Oh, D. Khong, E. Y. Wu, R. Manohar, C. Miller, et al., “Restoring Systemic Gdf11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle,” Science 344, no. 6184 (May 9, 2014): 649-52.
15. “Old muscles seemed to be rejuvenated by dosing with oxytocin”: C. Elabd, W. Cousin, P. Upadhyayula, R. Y. Chen, M. S. Chooljian, J. Li, S. Kung, K. P. Jiang, and I. M. Conboy, “Oxytocin Is an Age-Specific Circulating Hormone That Is Necessary for Muscle Maintenance and Regeneration,” Nature Communications 5 (2014): 4082.
Epilogue: The Death of Death
1. “It’s called cytomegalovirus”: P. Sansoni, R. Vescovini, F. F. Fagnoni, A. Akbar, R. Arens, Y. L. Chiu, L. Cicin-Sain, et al., “New Advances in Cmv and Immunosenescence,” Experimental Gerontology 55 (July 2014): 54-62. L. Cicin-Sain, J. D. Brien, J. L. Uhrlaub, A. Drabig, T. F. Marandu, and J. Nikolich-Zugich, “Cytomegalovirus Infection Impairs Immune Responses and Accentuates T-Cell Pool Changes Observed in Mice with Aging,” PLoS Pathogens 8, no. 8 (2012): e1002849.
2. “CMV is particularly strongly associated with preclinical cardiovascular disease”: N. C. Olson, M. F. Doyle, N. S. Jenny, S. A. Huber, B. M. Psaty, R. A. Kronmal, and R. P. Tracy, “Decreased Naive and Increased Memory Cd4(+) T Cells Are Associated with Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis.” [In English]. PLoS One 8, no. 8 (2013): e71498.
3. “In short, it’s like a guerrilla war”: Some scientists, notably Luigi Ferrucci of the NIA and The Blast, think that the job of cellular maintenance and repair is also under the domain of the immune system. So a virus like CMV would obviously help accelerate our aging, while the ability to restore a functioning thymus gland could have vast effects on the aging process generally. (People who take HGH also report that their thymus glands regrow, but they do not seem to work very well.)
4. “it was born in an epiphany that de Grey experienced”: The epiphany is described at the beginning of de Grey’s book, Ending Aging.
5. “a huge, $9 million EU-funded research initiative called ThymiStem”: The project has a website, http://www.thymistem.org; the 2014 paper can be found at N. Bredenkamp, C. S. Nowell, and C. C. Blackburn, “Regeneration of the Aged Thymus by a Single Transcription Factor,” Development 141, no. 8 (April 2014): 1627-37.
6. “food and energy prices would go ‘through the roof,’ ”: Randall Kuhn’s SENS6 talk can be found here in its entirety: www.youtube.com/watch?v=F2s-RdkAB_4.
7. “it is a mainspring of human activity”: Ernest Becker, The Denial of Death (New York: Free Press, 1973).
Appendix: Things That Might Work
Resveratrol:
Poulsen Morten Møller et al. “Resveratrol in metabolic health: an overview of the current evidence and perspectives,” in Annals of the New York Academy of Sciences. 1290 (2013) 74–82.
Hector et al. “The effect of resveratrol on longevity across species: a meta-analysis.” Biology Letters (2012) 8, 790–793. Published online June 20, 2012. Basically refutes the whole notion that resveratrol increases lifespan in any animal.
Mattison, J. A., M. Wang, M. Bernier, J. Zhang, S. S. Park, S. Maudsley, S. S. An, et al. “Resveratrol Prevents High Fat/Sucrose Diet-Induced Central Arterial Wall Inflammation and Stiffening in Nonhuman Primates.” Cell Metabolism 20, no. 1 (July 1 2014): 183-90.
Walle, T. “Bioavailability of Resveratrol.” Annals of the New York Academy of Sciences 1215 (January 2011): 9-15.
Rossi D., A. Guerrini, R. Bruni, E. Brognara, M. Borgatti, R. Gambari, S. Maietti, G. Sacchetti. “trans-Resveratrol in Nutraceuticals: Issues in Retail Quality and Effectiveness.” Molecules. 2012; 17(10):12393-12405. Addresses the lack of resveratrol in many alleged resveratrol supplements.
Weintraub, Arlene. “Resveratrol: The Hard Sell on Anti-Aging.” Businessweek, July 29, 2009. On the booming resveratrol supplement industry.
Alcohol/Red Wine:
Much of the relevant red-wine research is summed up elegantly in J. P. Broustet, “Red Wine and Health,” Heart 1999;81:459-460 (previously cited).
These guys reviewed ten large studies and found that ALL alcoholic drinks conferred some level of protection against cardiovascular disease. Rimm, Eric B., Arthur Klatsky, Diederick Grobbee, and Meir J Stampfer. “Review of Moderate Alcohol Consumption and Reduced Risk of Coronary Heart Disease: Is the Effect Due to Beer, Wine, or Spirits?” British Medical Journal Vol. 312,731. 1996.
This study is of particular note, because it was done in Bordeaux and because it found a tremendous protective effect of red wine against Alzheimer’s disease. The authors conclude, “There is no medical rationale to advise people over 65 to quit drinking wine moderately, as this habit carries no specific risk and may even be of some benefit for their health.” (Also, they define “moderate” drinking as 3-4 glasses/day.) Orgogozo, J. M., J. F. Dartigues, S. Lafont, L. Letenneur, D. Commenges, R. Salamon, S. Renaud, and M. B. Breteler. “Wine Consumption and Dementia in the Elderly: A Prospective Community Study in the Bordeaux Area.” [In English.] Revue Neurologique (Paris) 153, no. 3 (April 1997): 185-92.
More recent research is also suggesting that eating fat is not necessarily as bad for you as was thought when the “French Paradox” was coined in 1987—so the Paradox might not be such a paradox after all. Much of this is summed up in Teicholz, Nina.
The Big Fat Surprise: Why Butter, Meat, and Cheese Belong in a Healthy Diet. 1st Simon & Schuster hardcover ed. New York: Simon & Schuster, 2014.
Coffee:
The big review: Freedman, N. D., Y. Park, C. C. Abnet, A. R. Hollenbeck, and R. Sinha. “Association of Coffee Drinking with Total and Cause-Specific Mortality.” New England Journal of Medicine 366, no. 20 (May 17 2012): 1891-904.
Another big European study here: Floegel, Anna, Tobias Pischon, Manuela M. Bergmann, Birgit Teucher, Rudolf Kaaks, and Heiner Boeing. “Coffee Consumption and Risk of Chronic Disease in the European Prospective Investigation into Cancer and Nutrition (Epic)–Germany Study.” The American Journal of Clinical Nutrition 95, no. 4 (April 1, 2012): 901-08.
Thoughtful editorial to accompany the above: Lopez-Garcia, Esther. “Coffee Consumption and Risk of Chronic Diseases: Changing Our Views.” The American Journal of Clinical Nutrition 95, no. 4 (April 1, 2012): 787-88.
Curcumin:
See notes for p.85, which are on p. 328.
“Life Extension Mix”:
Spindler, S. R., P. L. Mote, and J. M. Flegal. “Lifespan Effects of Simple and Complex Nutraceutical Combinations Fed Isocalorically to Mice.” Age (Dordr) 36, no. 2 (April 2014): 705-18.
Metformin:
Martin-Montalvo, A., E. M. Mercken, S. J. Mitchell, H. H. Palacios, P. L. Mote, M. Scheibye-Knudsen, A. P. Gomes, et al. “Metformin Improves Healthspan and Lifespan in Mice.” Nature Communications 4 (2013): 2192.
DeCensi, Andrea, Matteo Puntoni, Pamela Goodwin, Massimiliano Cazzaniga, Alessandra Gennari, Bernardo Bonanni, and Sara Gandini. “Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-Analysis.” Cancer Prevention Research 3, no. 11 (November 1, 2010): 1451-61.
Kasznicki, J., A. Sliwinska, and J. Drzewoski. “Metformin in Cancer Prevention and Therapy.” Annals of Translational Medicine 2, no. 6 (June 2014): 57.
Vitamin D
Brunner, R. L., B. Cochrane, R. D. Jackson, J. Larson, C. Lewis, M. Limacher, M. Rosal, S. Shumaker, and R. Wallace. “Calcium, Vitamin D Supplementation, and Physical Function in the Women’s Health Initiative.” Journal of the American Diet Association 108, no. 9 (September 2008): 1472-9.
Bjelakovic, G., L. L. Gluud, D. Nikolova, K. Whitfield, J. Wetterslev, R. G. Simonetti, M. Bjelakovic, and C. Gluud. “Vitamin D Supplementation for Prevention of Mortality in Adults.” Cochrane Database Systematic Reviews 1 (2014): CD007470.
Holick, M. F. The Vitamin D Solution: A 3-Step Strategy to Cure Our Most Common Health Problem, (New York: Hudson Street Press, 2010).
Gordon Lithgow talks about the vitamin D story here: http://vimeo.com/channels/thebuck/67168737.
Aspirin and Ibuprofen
There are lots and lots of studies on aspirin and anti-inflammatories. The Womens’ Health Initiative study (same one that shot down hormone replacement) found a strong association between aspirin use and reduced mortality: Berger, J. S., D. L. Brown, G. L. Burke, A. Oberman, J. B. Kostis, R. D. Langer, N. D. Wong, and S. Wassertheil-Smoller. “Aspirin Use, Dose, and Clinical Outcomes in Postmenopausal Women with Stable Cardiovascular Disease: The Women’s Health Initiative Observational Study.” Circulatory and Cardiovascular Quality and Outcomes 2, no. 2 (March 2009): 78-87.
Strong, Randy, Richard A. Miller, et al. “Nordihydroguaiaretic Acid and Aspirin Increase Lifespan of Genetically Heterogeneous Male Mice.” Aging Cell 7, no. 5 (2008): 641-50. Found that it made mice live longer—males only.
Vlad, S. C., D. R. Miller, N. W. Kowall, and D. T. Felson. “Protective Effects of NSAIDs on the Development of Alzheimer Disease.” Neurology 70, no. 19 (May 6, 2008): 1672-7.
Kale
Only if you like the taste.
Further Reading
Agus, David. A Short Guide to a Long Life. New York: Simon & Schuster, 2014.
Agus, David, and Kristin Loberg. The End of Illness. 1st Free Press hardcover ed. New York: Free Press, 2012.
Alexander, Brian. Rapture: How Biotech Became the New Religion. 1st ed. New York: Basic Books, 2003.
Aminoff, Michael J. Brown-Séquard: An Improbable Genius Who Transformed Medicine. New York: Oxford University Press, 2010.
Arrison, Sonia. 100 Plus: How the Coming Age of Longevity Will Change Everything: From Careers and Relationships to Family and Faith. New York: Basic Books, 2011.
Austad, Steven N. Why We Age: What Science Is Discovering About the Body’s Journey through Life. New York: J. Wiley & Sons, 1997.
Becker, Ernest. The Denial of Death. New York: Free Press, 1973.
Boyle, T. Coraghessan. The Road to Wellville. New York: Viking, 1993.
Brock, Pope. Charlatan: America’s Most Dangerous Huckster, the Man Who Pursued Him, and the Age of Flimflam. 1st ed. New York: Crown Publishers, 2008.
Buettner, Dan. The Blue Zones: 9 Lessons for Living Longer from the People Who’ve Lived the Longest. 2nd ed. Washington, D.C.: National Geographic, 2012.
Campbell, T. Colin, and Thomas M. Campbell. The China Study: The Most Comprehensive Study of Nutrition Ever Conducted and the Startling Implications for Diet, Weight Loss and Long-Term Health. Dallas: BenBella Books, 2005.
Comfort, Alex. The Process of Ageing. Signet Science Library. New York: New American Library, 1964.
Comfort, Alex. Ageing, the Biology of Senescence. Rev. and reset ed. New York: Holt, 1964.
Cornaro, Luigi, Joseph Addison, Francis Bacon, and William Temple. The Art of Living Long; a New and Improved English Version of the Treatise. Milwaukee: W. F. Butler, 1905.
Cowdry, Edmund Vincent, and Edgar Allen. Problems of Ageing; Biological and Medical Aspects. 2nd ed. Baltimore: The Williams & Wilkins Company, 1942.
Critser, Greg. Eternity Soup: Inside the Quest to End Aging. 1st ed. New York: Harmony Books, 2010.
Crowley, Chris, and Henry S. Lodge. Younger Next Year: A Guide to Living Like 50 until You’re 80 and Beyond. New York: Workman Publishing, 2004.
De Grey, Aubrey D. N. J., and Michael Rae. Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. 1st ed. New York: St. Martin’s Press, 2007.
Finch, Caleb. Longevity, Senescence, and the Genome. The John D. and Catherine T. MacArthur Foundation Series on Mental Health and Development. Chicago: University of Chicago Press, 1990.
Finch, Caleb, and Leonard Hayflick. Handbook of the Biology of Aging. The Handbooks of Aging. New York: Van Nostrand Reinhold Co., 1977.
Gawande, Atul. Being Mortal: Medicine and What Matters in the End. 1st ed. New York: Metropolitan Books: Henry Holt & Company, 2014.
Gruman, Gerald J. A History of Ideas About the Prolongation of Life. Classics in Longevity and Aging Series. New York: Springer Publishing Co., 2003.
Guarente, Leonard. Ageless Quest: One Scientist’s Search for Genes That Prolong Youth. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 2003.
Hadler, Nortin M. The Last Well Person: How to Stay Well Despite the Health-Care System. Montreal; Ithaca: McGill-Queen’s University Press, 2004.
Haldane, J. B. S. New Paths in Genetics. London: G. Allen & Unwin Ltd., 1941.
Hall, Stephen S. Merchants of Immortality: Chasing the Dream of Human Life Extension. Boston: Houghton Mifflin, 2003.
Hayflick, Leonard. How and Why We Age. 1st ed. New York: Ballantine Books, 1994.
Holick, M. F. The Vitamin D Solution: A 3-Step Strategy to Cure Our Most Common Health Problem. New York: Hudson Street Press, 2010.
Jacobs, A. J. Drop Dead Healthy: One Man’s Humble Quest for Bodily Perfection. 1st Simon & Schuster hardcover ed. New York: Simon & Schuster, 2012.
Jerome, John. Staying With It. New York: Viking Press, 1984.
Kerasote, Ted. Pukka’s Promise: The Quest for Longer-Lived Dogs. Boston: Houghton Mifflin Harcourt, 2013.
Kurzweil, Ray, and Terry Grossman. Transcend: Nine Steps to Living Well Forever. Emmaus, PA: Rodale, 2009.
Lakatta, E. G. “Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enter
prises: Part III: Cellular and Molecular Clues to Heart and Arterial Aging.” Circulation 107, no. 3 (Jan 28 2003): 490-7.
Lakatta, E. G., and D. Levy. “Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part II: The Aging Heart in Health: Links to Heart Disease.” Circulation 107, no. 2 (Jan 21 2003): 346-54.
———. “Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part I: Aging Arteries: A ‘Set up’ for Vascular Disease.” Circulation 107, no. 1 (Jan 7 2003): 139-46.
Lieberman, Daniel. The Story of the Human Body: Evolution, Health, and Disease. 1st ed. New York: Pantheon Books, 2013.
Life, Jeffry S. The Life Plan: How Any Man Can Achieve Lasting Health, Great Sex, and a Stronger, Leaner Body. 1st Atria Books hardcover ed. New York: Atria Books, 2011.
Masoro, Edward J., and Steven N. Austad. Handbook of the Biology of Aging. The Handbooks of Aging. 6th ed. Amsterdam; Boston: Elsevier Academic Press, 2006.
McCay, Jeanette B. Clive McCay, Nutrition Pioneer: Biographical Memoirs by His Wife. Charlotte Harbor, FL: Tabby House, 1994.
Mitchell, Stephen. Gilgamesh: A New English Version. New York: Free Press, 2004.
Moalem, Sharon, and Jonathan Prince. Survival of the Sickest: A Medical Maverick Discovers Why We Need Disease. 1st ed. New York: William Morrow, 2007.
Mosley, Michael, and Mimi Spencer. The Fast Diet: Lose Weight, Stay Healthy, and Live Longer with the Simple Secret of Intermittent Fasting. 1st Atria Books hardcover ed. New York: Atria Books, 2013.