This chapter focuses on increasing longevity and efforts to cure age-related diseases. The following chapter discusses how these advances may affect us socially.
For centuries, futurists predicted that science would offer humans longer lives; Enthusiasts predicted that science would conquer death. Within the past two generations, medicine has put some meat on those predictive bones, extending lives of citizens by twenty years in developed countries .
The longest documented human life belonged to Jeanne Calment, a Frenchwoman who died in 1997 at 122. Next came a Japanese woman, Shigechiyo Izumi, who lived to 120, followed by Americans Sarah Knauss, 119, Canadian Marie-Louise Meilleur, 118, and Lucy Hannah, 117.[1] The Gerontology Research Group of the Guinness Book of Records verified that over one hundred humans, all women, have lived to 113.[2]
Researchers at Mt. Sinai Hospital in New York study dozens of SuperAgers in New York City, a cohort of Ashkenazic Jews who commonly live well beyond 100 years. They seem to possess four genes that protect against cancer, cardiovascular disease and diabetes, dementia, and atherosclerosis.[3] The expected results, combined with a blood test for the length of telomeres at mid-age, may create a blood test that predicts when your body will fall apart.[4]
In 2006, 2.4 million Americans died; 4.7 million newborns replaced them.[5] According to the U.S. Census Bureau, by June 2008, the world had 6.7 billion humans.[6] Every year, 80 million more people begin life on Earth than leave it (135 million begin, 55 million leave). As such, world population by 2012 should reach 7 billion.
For the average human, expected longevity improved from an estimated twenty-five years in 15,000 B.C. to thirty-five years in the time of Sparta. In the United States, expected longevity has improved from forty-seven years in 1900 to sixty-five years in 1950 to seventy-five years in 1990 to eighty years in 2011.[7]
Over the past 160 years, American longevity has increased about 2.5 years per decade. Women generally outlive men by three years. For future women, expected longevity at age 50 will be 88 years in 2024 and 100 years in 2104.[8] (More later on these amazing facts and what they imply.)
What enables people to live longer now stems from progress started long ago. To strengthen his country, Otto von Bismarck, Prime Minister of Prussia for the latter half of the nineteenth century, started many reforms in public health, such as mandatory public sanitation, clean water, and public education. Physician Rudolf Virchow had already taught the view that better social and economic conditions could improve the health of citizens, a view known sometimes as “social medicine.” Together, Virchow and Bismarck revolutionized thinking about health and longevity. In 1883, Bismarck also founded a national pension system for old age and decided that retirement began at age sixty-five, an age still used—perhaps incorrectly—in America today for eligibility for Medicare.
Bismarck’s and Virchow’s ideas, along with other advances, helped increase longevity, especially clean water and sanitation, vaccinations, acceptance of the germ theory of disease around 1900, discovery of antibiotics in the 1940s, improved occupational safety, and defeat of lethal childhood illnesses. Simple things such as seat belts, lower speed limits, and cars with multiple air bags also helped.
Human longevity increased in developed countries by stacking lots of big and small improvements. I shall return to this fact at the end of this chapter, but first I want to consider prospects for rapid increases in longevity or even a cure for death.
Biologist Leonard Hayflick discovered in 1965 that the maximal human life span is fixed at about 125 years. Doubling that would be a feat requiring stupendous discoveries and a fantastic commitment by the public to fund new research in biology.
Why is it so difficult to cure aging at the cellular level? A basic fact of biology is that cells can only divide so many times (about fifty). Cells have a built-in destiny to die at some point, an event called apoptosis. Telomeres, like the plastic caps on the ends of shoelaces, keep our cellular shoelaces from fraying. Each time a cell replicates through mitosis, its telomeres shorten.
How many times telomeres can shorten before they die (enter senescence) is their Hayflick limit, named for Hayflick’s discovery of this fact.[9] Cells of different species have different Hayflick limits and, hence, different life spans.
The enzyme telomerase keeps telomeres healthy and appears to be the key to slowing down aging at the cellular level. Why not give cells more telomerase, restoring what telomeres lose in mitosis, and stop cellular aging?
Unfortunately, doing so would probably cause cancer. Forcing a cell to die (when its telomeres are too short) keeps it from growing out of control (cancer is essentially this). When cells replicate, DNA on the tips can mutate and become unstable. While this happens all the time, the p53 gene kills out-of-control cells, stopping cancer in the body by shortening the cell’s telomeres and making the cancerous cell die.[10] Thus, if you prevent telomeres from shortening and block the p53 gene’s action, you prevent the body from stopping cancer. UAB biology professor Trygve Tollefsbol, an expert on aging and telomeres, says, “Aging can be seen as a tumor suppressor mechanism.”[11]
Hayflick distinguished between trying to reverse aging at the cellular level and trying to cure age-related diseases. He claims that if we cured cardiovascular disease, cancer, and stroke, we would only increase life expectancy by fifteen years.[12]
Hayflick’s distinction is valuable. For one thing, he criticizes the conflation of research into aging-related diseases with research to stop aging. The latter goal, obviously, is much more difficult to achieve. The distinction also allows us to make another, namely between life span and life expectancy. The human species’ maximal life span may be 125 years, but the average human life expectancy is far less than that. If nothing else, modern medicine could move us closer to our optimal life span.
Conquering aging at the cellular level would be a momentous undertaking. It would require a commitment of resources like those for building the Panama Canal or putting a man on the moon. To do so would take tremendous political will and public consensus.
Nevertheless, breakthroughs could occur. In 1996, textbooks of cellular biology stated that it was a law of nature that once cells became differentiated, they could not be returned to a pluripotent state. Steed Willadsen proved that wrong, opening the doors to not only the cloning of Dolly but also knowledge of stem cells.[13] Others later discovered adult stem cells and idiopathic pluripotent stem cells—all of which were previously unknown. As this book went to press, two major studies in mice, one about a drug that reduces fat in livers and increases sensitivity to insulin (SRT-1720,), and another about a discovery of senescent cells, hoped to be seminal breakthroughs that might one day translate into retarding human aging at the cellular level.[14]
We should keep an open mind about fixed limits and continue studying.
One key approach to anti-aging research is to study chemicals produced when the body starves. Rats fed 35 to 70 percent less calories live 25 to 40 percent longer. If such chemicals could be reproduced and safely injected into cells, perhaps the body could be fooled into thinking it was starving when a person ate normally.[15]
One company identified this substance as resversatrol, a substance found in the skin of red grapes. This substance lies behind the so-called “French paradox,” the fact that Frenchmen eat foods high in saturated fats but have low incidences of coronary artery disease. Their consumption of resversatrol in red wine is alleged to explain this paradox, and after a segment was aired in 1991 on “60 Minutes” about this effect, consumption of red wine in America jumped 44 percent (and wine companies lobbied to label red wine a “health food”). Unfortunately, a decade of well-funded scientific studies has failed to confirm any anti-aging benefits of taking resveratrol in concentrated forms.[16]
Another chemical approach to anti-aging research is taking megadoses of vitamins in attempts to counteract the damage caused by free radicals inside cells. Anti-aging researcher Jay Olshansky dismisses this approach as “a way to make expensive urine.”[17]
To maintain muscles and to combat fragility, others inject human growth hormone, but the benefits are no better than those of exercise. Also, the dangers of injection (infection at the site) can be huge.
More philosophically, we should emphasize that most people don't want extra decades of being feeble or senile, but rather extra decades with compression of morbidity. We want to play tennis right up to the last month, and then have everything break down at once, like the famous one-horse shay of Oliver Wendell Holmes.[18]
Gerontologists long ago redefined aging from chronological criteria.[19] If a woman can do all the activities of a normal forty-year-old, why should she be classified by the old standards of what sixty-year-olds can do? Indeed, a functional definition of aging much more accurately represents the reality of a person’s life and corresponds with what one sees in a hospital.[20] Defined by the ability to do or not to do a dozen “Activities of Daily Living” (ADLs), such as walking, driving, cleaning, and eating, these criteria much more accurately measure how old a person is. They measure how well a man can live by himself and act as humans normally do. For example, a fifty-year-old man with congestive heart failure who cannot walk to the corner is the functional equivalent of a ninety-year-old man.
But do we need drugs and surgery to live longer? A lot of medical evidence indicates that living healthfully over decades is the best way to make a body live longer. In the twenty-first century, epidemiologists can give better advice about how to do this. Consider a summary by two leading Harvard researchers of new evidence about the role of diet and exercise in preventing—not type 2 diabetes or heart disease—but cancer.[21] They write:
We’ve known for a long time that a high-fat diet, obesity, and lack of exercise can increase the risk of developing heart disease and type-2 diabetes, two conditions that affect millions of Americans. What we are finding out now is that those same lifestyle factors also play an important role in cancer. That’s bad news. The good news is that you can do something about your lifestyle. If we grew thinner, exercised regularly, avoided diets rich in red meat … and ate diets rich in fruits and vegetables, and stopped using tobacco, we would prevent 70 percent of all cancers.
That’s an amazing claim. Seven in ten cancers could be prevented by relatively simple changes in how we live. This new evidence contradicts the fatalistic view that most cancer stems from the genes. In fact, genes alone determine only a tiny percentage of breast, ovarian, and other cancers.
The evidence behind the claim is also impressive. People with the same genes, say, Asians, who adopt a Western lifestyle of no exercise, high-fat, red meat diets, and who put on pounds, suddenly start to develop breast, colon, and other cancers at the high rates found among North Americans living the same Western lifestyle.
Even people who had cancer can decrease their chances of recurrence by changing their ways. People with colon cancer who continued to eat badly, even after part of their colon was removed to excise their cancer, had three times more risk of cancer returning than people who changed their diet.
Both Alarmists and Enthusiasts often talk of the implications of a miraculous anti-aging pill, yet the implications of the evidence just presented are that this pill already exists: all we need to do is change how we live.
Marriage also factors into longevity. Marriage reduces the risks of early death and contributes to good health, especially for men.[22] (Epidemiologists dispute the exact causes: does ill health discourage marriage? Do healthier men get married easily? Are young men who marry early already healthier?)
Consider also exercise training in senior citizens that prevents loss of muscle. From age thirty to age fifty, people lose up to 10 percent of their muscle mass, but from ages fifty to eighty, they typically lose another 30 percent. One approach to preventing this loss, weight training, helps seniors retain such mass.
New studies show that weight training plans designed to stimulate synthesis of protein for growth of new muscle in young people are not as effective in those over sixty, who generally seem to have a blunted protein synthesis response to each exercise bout and appear more susceptible to muscle inflammation.[23] So how can seniors maintain muscle mass, or regrow lost muscle through exercise?
The answer lies in reducing exercise from three to two times a week and in modifying the eccentric exercises. Most injuries stem from lowering weights, not lifting them, so seniors should lift objects, not lower them.[24] According to University of Alabama at Birmingham professor of physiology Marcus Bamman, the benefits of this extra recovery time between exercise sessions for older adults likely stem from both enhanced muscle protein synthesis and stem cell activity, as well as reduced inflammation.
Beyond this modest method of reducing loss of muscle is the revolutionary proposal that each adult over fifty should get an individualized exercise prescription. Professor Bamman states,
I would love for people to appreciate that an exercise prescription could be approached exactly like a drug prescription. There’s a proper dosage and a time-course for it to wash out.[25]
Wow! What a great idea! Can you imagine a different kind of medicine where healthy patients had not only a primary care physician, but also a personal exercise prescription? I’m not talking about personal trainers but rather a person with an advanced degree in exercise physiology and nutrition. That is far different from our present system.
Finally, consider an issue close to enhancing mood. What if we could quickly lose weight with a pill? Would traditionalists want to ban it, arguing that we should only lose weight the approved way, through willpower, diet, and exercise? In 2008, reports emerged of a miraculous pill that, when given to mice, allegedly created the same physiological and metabolic good effects as if they had exercised.[26] If it carried over to humans, taking this pill would give people the beneficial effects of exercise without exercising. Francis Collins testified in 2002 before the President’s Council of Bioethics that such a new pill “will help normal people be more svelte than they otherwise would be.”[27]
Imagine that you could eat as much as you wanted and really not gain weight—perhaps because the drug metabolizes extra food in a different way, making it quickly pass through the gastrointestinal tract, or that it helps cap your serum cholesterol levels. Wouldn’t that be a really different kind of life? For some people, it might even qualify as a Fukuyamaesque, post-human future. Would some women give up their humanity to eat as much as they pleased? Would some men do the same and gladly become satiated post-humans?
The most exciting development about longevity is that we may have quietly increased human longevity by a decade and nobody noticed. An exciting article by biodemographer James Vaupel in a March 2010 issue of Nature announced a “fundamental discovery about the biology of human aging, . . . one with profound implications for individuals, society, and the economy.”[28] This discovery, first substantiated in 1994, is that more and more people in developed countries are reaching old age in good health. Not only is death being delayed, but people are getting an extra decade of functional living.
The implications of this finding will reverberate through future discussions of intergenerational ethics and public policy. Vaupel writes that “most children born since 2000 will celebrate their 100th birthday—in the twenty-second century. Longer life spans will alter the way individuals want to allocate time during their lives and will require radical revisions of employment, retirement, health, education, and other policies.”[29]
As explained at the beginning of this chapter, this advance did not come from a sensational breakthrough in altering genes or some anti-aging elixir. Instead, it came about incrementally from stacking many different enhancements: “The progress made in lengthening life spans and postponing senescence is entirely due to medical and public health efforts, rising standards of living, better education, healthier nutrition, and more salubrious lifestyles.”[30]
The cynic typically responds to news about increased longevity with quips such as, “Great! Two decades in a nursing home rather than one!” But the increase in longevity is not being accompanied by dysfunction and senescence: “The process of deterioration with age is not being slowed over time: it is being delayed.” Moreover, “levels of mortality and other indices of health that used to prevail at age 70 now prevail at age 80, and levels that used to prevail at age 80 now prevail at age 90.”
Other evidence seems to confirm this trend. According to a 2000 Harris poll conducted by the National Council on Aging, half of Americans ages sixty-five to sixty-nine who were surveyed did not consider themselves “old-aged” but merely “middle-aged.”[31] The new trend may force us to rethink the concept of old age.
Prosperity and the tools of modern medicine mainly explain the delay of the usual ills that come in our seventies and eighties. This result appears evenly spread over North America, Japan, and Europe. As Vaupel concludes, “Most people in richer countries … can look forward to long, healthy lives. This is arguably the most important achievement of modern civilization.”[32]
In the next chapter, I explore the implications of Vaupel’s finding and clear up any confusions about what extending longevity means.
Jason Epstein, “The World’s Oldest Living Humans.” www.recordholders.org/en/list/oldest.html . See also Bernard Jeune and James W Vaupel, Validation of Exceptional Longevity, Odense Monographs on Population Aging Vol. 6, University Press of Southern Denmark, 1999 (English).
“List of Verified Oldest People,” Wikepedia. http://en.wikipedia.org/wiki/List_of_the_oldest_people. Guinness World Records 2008, Hit Publications.
Jesse Green, “What Do a Bunch of Old Jews Know about Living Forever?” New York Magazine, November 14, 2011, 28-33, 96-98.
Andrew Pollack, “A Blood Test May Offer Aging Clues,” New York Times, May 19, 2011, B1.
National Center for Health Statistics. www.cdc.gov/nchs/data/nvr56/nvr56_07.pdf
U.S. Census Bureau, International Data Base, “Total Midyear Population for the World: 1950–2050.” http://www.census.gov/ipc/www/idb/worldpo html
“Life Expectancy and Mortality,” Centers for Disease Control, Health, United States, 2007, with Chartbook on Trends and Health of Americans, 8. http://www.cdc.gov/nchs/data/hus/hus07.pdf#027. See also Mike Stobbe, “US Life Expectancy tops 78 for First Time,” Associated Press, Birmingham News, June 12, 2008, A3.
Adding 3.5 years to those over age 50 and 2.5 years per decade after 2004.
Leonard Hayflick, ”The Limited in vitro Lifetime of Human Diploid Cell Strains. Experimental Cell Research 37 (1965), 614–36.
Nicholas Wade, “Cancer Fighter Exacts a Price: Cellular Aging,” New York Times, January 8, 2002, D1.
Trygve Tollefsbol, quoted in “The Building Blocks of Death, by Kathleen Yount, UAB Magazine, Spring 2008, 17. Also, personal communication of T. Tollefsbol to author, January 31, 2012.
Leonard Hayflick, review of The Quest for Immortality, by S. Olshansky, in Radiation Research 156 (2001), 334.
Gina Kolata, Clone: The Path to Dolly, and Road Ahead, New York, Harper, 1998.
Nicholas Wade, “Lives for Obese Mice, with Hope for Humans of All Sizes,” New York Times, August 19, 2011, A1; “Prospect of Delaying Aging Ills is Raised in Cell Study in Mice,” November 3, 2011, A1.
Ronald Bailey, Liberation Biology, 46.
Nicholas Wade, “Longevity Research Raises Hopes and Questions,” New York Times, September 22, 2011, A19.
Jay Olshansky, quoted by Ron Bailey in “Forever Young,” Reason, August/September 2002. http://reason.com/archives/2002/08/01/forever-young/singlepage
Oliver Wendell Holmes, “The Deacon’s Masterpiece or, the Wonderful ‘One-hoss Shay’: A Logical Story.”
Have you heard of the wonderful one-horse shay,
That was built in such a logical way.
It ran a hundred years to a day,
And then, of a sudden, it — ah, but stay,
. . . The poor old chaise in a heap or mound
As if it had been to the mill and ground!
You see, of course, if you’re not a dunce,
How it went to pieces all at once,
—All at once, and nothing first,
Just as bubbles do when they burst.
J. E. Graham et al, “Dynamics of Cognitive Aging: Distinguishing Functional Age and Disease from Chronologic Age in a Population,” American Journal of Epidemiology 150 (1999), 1045–54.
“Preventive Gerontology: Strategies for Optimizing Health Across the Life Span,” Principles of Geriatric Medicine and Gerontology, ed. N. Honza et al., McGraw-Hill, 2003, 90. See also Robert Kane et al., Essentials of Clinical Geriatrics, 5th ed. McGraw-Hill, 2004, 54–55.
Robert Weinberg and Anthony Komaroof, “Your Lifestyle, Your Genes, and Cancer,” Newsweek, June 23, 2008, 41–43.
Rand Corporation Report, “Health, Marriage, and Longer Life for Men,” 1998.
http://www.rand.org/pubs/research_briefs/RB5018/index1.html. Lee A. Lillard and Constantijn W.A. Panis, "Marital Status and Mortality: The Role of Health," Demography, 33, no. 3 (1996), 313–27; H. Liuand and D.J. Umberson, “The times they are a changin’: Marital status and health differentials from 1972 to 2003,” Journal of Health and Social Behavior 49, no. 3, 2008.
J. K. Petrella et al, “Potent Myofiber Hypertrophy During Resistance Training in Humans is Associated with Satellite Cell-Mediated Myonuclear Addition: A Cluster Analysis,” Journal of Applied Physiology 1, April 2008.
Matt Windsor, quoting Marcus Bamman in “Strong Medicine: Prescription for a Better Life,” UAB Magazine, Spring 2008, 13. Also, personal communication to author from Marcus Bamman, January 31, 2012.
Matt Windsor, quoting Marcus Bamman in “Strong Medicine: Prescription for a Better Life,” UAB Magazine, Spring 2008, 13. See also D.J. Kosek and M. M. Bamman, “Modulation of the dystrophin-associated protein complex in response to resistance training in young and older men,” Journal of Applied Physiology 104, no. 5, May 2008, 1476–84.
Mark Schoofs and Ron Winslow, “Just Sitting Back to Get in Shape: Two Pills Do the Work of Exercise,” Wall Street Journal, August 1, 2008, A1.
Francis S. Collins, “Genetic Enhancements: Current and Future Prospects,” December 13, 2002. Transcripts, President’s Council on Bioethics.
James Vaupel, “Biodemography of Human Ageing,” Nature, 464, 25 March 2010, 536–42.
James Vaupel, “Biodemography of Human Ageing,” 536.
James Vaupel, “Biodemography of Human Ageing,” 536.
National Council on Aging, Press Release, “Nearly Half of Older Americans Say, ‘These Are Best Years Of My Life, National Survey Shows,” March 29, 2010.
James Vaupel, “Biodemography of Human Ageing,” 537.