Forever young

As the Gilgamesh saga, Ponce de Leon's quest for the Fountain of Youth, and the alchemists' search for the philosopher's stone all attest, the yearning for eternal life and youth has been a preoccupation of humans for millennia. Yet quite a few people remain unconvinced that cheating death is a good idea.

“Living too long is a loss,” the oncologist and bioethicist Ezekiel Emanuel wrote in a widely cited Atlantic article this past October, provocatively titled “Why I hope to die at 75.” “It renders many of us, if not disabled, then faltering and declining, a state that may not be worse than death but is nonetheless deprived.” Emanuel added, “It robs us of our creativity and ability to contribute to work, society, the world.”

“The longer lives that medical advances have given us have run exactly parallel to the increase in chronic illness and the explosion in costs,” wrote Daniel Callahan, founder of the Hastings Center, a bioethics think tank, in a 2013 New York Times op-ed. “Can we possibly afford to live even longer—much less radically longer?”

“It’s worse than you think,” fretted Harvard political scientist Gary King and Dartmouth demographer Samir Soneji in a New York Times op-ed on the future of Social Security the same year. “If the amount of money coming in through payroll taxes does not increase and if the amount of money going out as benefits remains the same, the trust funds will become insolvent less than 20 years from now.”

For every promising advance in cancer treatment or hip replacement, a chorus chimes in with a warning about being careful what we wish for: Sure, we’re curing diseases and easing pain, but perhaps the cost—in health and in dollars—is too high.

This approach isn’t just wrong; it’s almost criminally obtuse. These objections conflate the physical process of aging with the mere passage of years. Our quest must be—as it has been for all of recorded history—not merely to live a long time, but to slow and stop the process of aging. Eternal youth, not just long life.

The current medical paradigm is to go after each individual disease as it emerges in a perpetual game of therapeutic whack-a-mole. The result is that individuals begin to accumulate infirmities. About 50 percent of Medicare beneficiaries are being treated for five different chronic conditions. This is ultimately a losing proposition, because aging bodies accrue more and more lethal and disabling conditions that compete to kill them. Patients routinely survive health crises that would have done them in even a generation earlier, but to what end? If an older patient doesn’t die of a heart attack, prostate cancer could do him in. If a stroke doesn’t get her, the Alzheimer’s will. Ultimately, more than 25 percent of Medicare spending goes toward the 5 percent of beneficiaries who die each year.

There is a better way. We must look beyond individual pathologies to their root, aging itself. If anti-aging treatments can maintain people in the state of health of the average 30-year-old, the onset of chronic illnesses will be forestalled and health care and pension expenditures will be much lower. And it increasingly looks like we may actually be able to slow or even stop the aging process.

Everyone knows that as people get older they become more vulnerable to all sorts of diseases and chronic disabilities. The annual incidence rate for heart attacks, for example, is just 0.3 per 10,000 people before age 35. This rises inexorably to 66 per 10,000 for people who are between 65 and 74 years of age, eventually reaching 190 per 10,000 people for those over age 85.

The good news is that the age-adjusted death rate from coronary artery disease has fallen enormously over the past six decades, dropping from its peak of 482 deaths per 100,000 Americans in 1968 to 114 per 100,000 in 2010. This trend means that 1.2 million deaths from coronary artery disease were averted in 2010 alone. Nevertheless, cardiovascular disease remains the leading cause of death and disability in the United States.

Similarly, the probability of developing cancer goes up with advancing age. According to the National Cancer Institute, Americans have a 5.4 percent chance of developing cancer and a 2.2 percent chance of dying from the disease before age 45. The probability of developing cancer climbs to 24 percent between ages 55 and 64, while the chance of dying increases to nearly 19 percent. About 77 percent of all cancers are diagnosed in people 55 years of age and older. In 2012, the Centers for Medicare and Medicaid Services reported that 71 percent of Medicare beneficiaries suffer from at least two chronic conditions. The Centers for Disease Control and Prevention estimates that treating chronic diseases accounts for about 75 percent of total health system costs. In a 2013 report, the Congressional Budget Office projected that two-thirds of 65-year-olds likely will need assistance to deal with a loss in physical and/or cognitive functioning at some point during their remaining years of life.

All this treatment is expensive. Really expensive. In 2013, U.S. health care spending reached $2.9 trillion, more than 17 percent of the country’s gross domestic product (GDP). Medicare spending was $586 billion, about 20 percent of all national health spending in 2013. Nearly 30 percent of Medicare spending—about $170 billion—was spent on patients’ last six months of life.

There are also old-age entitlements to consider. At the moment, the elderly expect to be showered with retirement and medical benefits as soon as their cake has enough candles. U.S. life expectancy was just 63 years in 1940 when the first monthly Social Security check was made to Ida May Fuller in the amount of $22.54. Ms. Fuller, who had paid a total of $24.75 into Social Security, eventually received $22,888.92 in benefits by the time she died in 1975 at the age of 100. But she was lucky: In 1940, the percentage of the men who survived from age 21 to 65 (their working lives) was 54 percent, and for women it was 61 percent. By 2010, those figures rose to 78 percent and 87 percent, respectively. Since 1940, life expectancy has risen to 78.8, an increase of nearly 16 years. The Social Security Administration currently projects that the average life expectancy will be 84.8 years in 2060.

Absent significant policy change, longer lives mean larger outlays. In July, the Congressional Budget Office identified an aging population as the key driver of increased retirement and medical spending, accounting for 55 percent of the projected growth in federal spending for Social Security and the major health care programs as a share of GDP through 2039.

What’s more, when you ask people about whether they’d like to live longer lives they have decidedly mixed feelings. A 2012 poll commissioned by the drug company Pfizer reported that 64 percent of those surveyed said they were most afraid of losing independence or living in pain. Even more starkly, in a 2005 survey by the Massachusetts AARP, nine out of 10 respondents answered that total physical dependency would be worse than death. In other words, their primary worry is a drawn-out period of infirmity, with very low quality of life. And they’re also worried about who’s going to pay for all of those extra years. A 2010 poll of Americans ages 44 to 75 by the Allianz Insurance Company found that 61 percent said they fear depleting their assets more than they fear dying.

Now let’s look at these problems again, concentrating not on long life but on long youth. If bodies can be kept young, they will be less vulnerable to diseases at any chronological age. If 55 really were physiologically the new 45, the incidence of cardiovascular disease would go down by about 50 percent and the prevalence of cancer would be cut by nearly 80 percent. “A modest deceleration in the rate of biological aging would produce the equivalent of simultaneous major breakthroughs against every single fatal and nonfatal disease associated with growing older,” observed the University of Illinois at Chicago demographer Jay Olshansky and his colleagues in a 2006 article for The Scientist.

Bodies age in much the same way that automobiles do. In the course of roaming around the world, they accumulate damage, which, if not repaired, leads to a breakdown. Unlike automobiles, human bodies do have some capacity for fending off hurts and for self-repair, but those mechanisms eventually wear out.

Fortunately, researchers are making considerable progress in figuring out credible ways to repair the damage and thus slow down the aging process. “We have good reasons to think that slowing the aging in humans is scientifically plausible and, given sufficient research investment, might prove to be within our technical grasp in the foreseeable future,” Olshansky and his colleagues asserted.

The cells in our bodies divide a number of times over the course of our lives, but they ultimately stop and become senescent. Organs and tissues are also replenished from stockpiles of stem cells that can renew themselves, but they eventually falter. Researchers such as James Kirkland, director of the Mayo Clinic’s Robert and Arlene Kogod Center on Aging, suggest that cells stop dividing and become senescent as a way to prevent them from being cancerous. In younger bodies senescent cells are generally killed off by immune cells called macrophages. But senescent cells secrete substances that reduce macrophage responsiveness and that induce inflammation in healthy cells and tissues. Researchers have found that the buildup of senescent cells correlates strongly with all sorts of maladies that increase with age, including frailty, diabetes, heart disease, dementia, eye diseases, bone and joint diseases, and cancers. This suggests that killing off senescent cells might increase healthspan and lifespan.

To check this hypothesis, Mayo Clinic researchers created genetically modified mice that accumulate senescent cells quickly and thus appear to develop lots of age-related disorders quickly, including cataracts, muscle weakening, thinning skin, and cardiac arrhythmias. The scientists also made the senescent cells susceptible to a killer drug that was attracted to a specific compound that they secrete. In a 2011 Nature article they reported that removing the senescent cells using the drug significantly delayed the onset of the age-related disorders. They concluded that the research indicates “that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.” The search is on for possible senolytic drugs that would slow aging by eliminating senescent cells.

Another possible way to slow aging is to prevent cells from becoming senescent in the first place. Some research suggests that the immunosuppressant drug rapamycin and the diabetes drug metformin do stop cells from becoming senescent by encouraging cells to repair damage to themselves. Dosing mice with rapamycin increases their physical fitness, improves their cognition and cardiovascular health, and cuts their cancer rates; they live about 15 percent longer than untreated mice.

One more possible cause of aging is the decline in the regenerative capacity of stem cells and/or the exhaustion of the stem cell pool in adult tissues and organs. Stem cells can transform and proliferate to replace worn-out cells in the adult organs and tissues in which they reside. Can the capacity of adult stem cells be restored so that they can repair and replace damaged tissues and organs in older adults?

In 2014, Harvard stem cell researchers Amy Wagers and Richard Lee reported the results of experiments in which they surgically stitched the circulatory systems of young mice to those of old mice. They found that factors in the blood of young mice enhanced the functionality of adult stem cells in the old mice, so that they rejuvenated muscle and heart tissue and improved blood flow to the brains of the old mice. That, in turn, sparked the growth of new brain cells. They isolated a protein from the blood of young mice called GDF11 and injected it into old mice, where it had essentially the same rejuvenating effects. The researchers are now talking to venture capitalists about financing a company that would aim to bring GDF11 into human trials.

The 2013 launch of the anti-aging company Calico—created by the founders of Google, with former Genentech board Chairman Art Levinson in charge—is a pretty good sign that anti-aging therapies are becoming a real prospect.

But what about the bottom line? Is it a better fiscal proposition to keep paying for grandma’s Plavix or to try to figure out how to keep her young instead? In 2013, a team of health economists led by the University of Southern California’s Dana Goldman tried to answer that question. Their Health Affairs study simulated the health trajectory of older cohorts under four life expectancy scenarios as a way to estimate the evolution of health spending through 2060.

The four scenarios included a baseline with no disease changes, a scenario in which cancer incidence was reduced by 25 percent, another in which heart disease prevalence dropped 25 percent, and one in which aging was delayed by 2.2 years. These scenarios are quite modest; they assume that medical progress affecting the healthspans and lifespans of people who reach the age of 51 by 2030 essentially stops between then and 2060.

In these simulations, life expectancy at age 51 in 2030 in the baseline scenario was another 35.8 years; delayed cancer, 36.9 years; delayed heart disease, 36.6 years; and delayed aging, 38 years. For what it’s worth, the Social Security Administration estimates that the current life expectancy for a 51-year-old is 28.6 years. In the baseline scenario, the number of Americans over age 65 rises from 43 million in 2010 to 106 million in 2060. Delayed cancer and heart disease boost that number by 0.8 and 2 percent, respectively. Delayed aging adds nearly 7 percent more people over 65 to the population by 2060.

Assuming no changes in the age thresholds at which Medicare and Social Security entitlements vest, Goldman and his colleagues calculate that by 2060 delayed heart disease would reduce Medicare expenditures in 2010 dollars by $60 billion below baseline, and delayed cancer would increase them by $80 billion. Delayed aging would boost 2060 Medicare spending by $295 billion, largely because there would be considerably more people enrolled in the program.

Similarly, delayed cancer and delayed heart disease would expand Social Security annual outlays in 2060 over the projected baseline by about $35 billion and $12 billion, respectively. Delayed aging increases those payments to an extra $125 billion by 2055 and falls off slightly thereafter. Between 2010 and 2060, the delayed aging scenario would boost entitlement spending, in constant 2010 dollars, by a total of $3 trillion over the baseline scenario, again because more people would be alive to receive benefits.

In other words, an older, healthier population looks pretty expensive. To procure a fiscal longevity dividend, Goldman and his colleagues argue for an “eligibility fix.” They note that in 1983 Congress set up a gradual process in which the threshold for receiving full Social Security benefits rises from 65 to 67 years of age. Their proposed eligibility fix for their delayed aging scenario would gradually increase Medicare eligibility from 65 to 68 and Social Security from 67 to 68. Such a fix would reduce combined Medicare and Social Security outlays, in 2010 dollars, by a total of $500 billion between 2010 and 2060.

But to fret about Social Security payouts is to miss the forest for the trees. “Ask yourself: what do you have now, and what do you covet, that you would not gladly trade for, say, five extra years?” Michael Kinsley wrote in The New Yorker in 2008.

Kinsley was then at the ripe old age of 57. As it happens, statisticians have tried to answer Kinsley’s question. Based on various calculations of what people appear to be willing to pay to avoid deleterious outcomes or to accept hazardous jobs, statisticians conservatively conclude that people on average value a year of life at about $100,000. Using this value, Goldman and colleagues estimate that between 2010 and 2060 their delayed aging scenario “yields a social benefit of approximately $7.1 trillion.”

Perhaps this estimate of the benefits of longer lives is too low. In a 2006 National Bureau of Economic Research study, University of Chicago economists Kevin Murphy and Robert Topol used a similar willingness-to-pay metric to calculate the value of the increase in longevity in the United States—newly produced life-years—over the 20th century. They argue, for example, that men gained additional life-years worth roughly $1 million over that period.

Over the course of the 20th century, the average life expectancy of a 30-year-old man increased from 34.9 years to 46.2 years. As a thought experiment, theauthors invite doubters to contemplate “a current 30-year-old who is offered the choice of (a) his current standard of living and health or (b) a lump sum of $1 million and the life expectancy of a 30-year-old in 1900, which is 11.3 years shorter.” Murphy and Topol further calculate that the reductions in mortality between 1970 and 2000 had an uncounted economic value of $3.2 trillion dollars per year, yielding total value of $95 trillion over that period. Goldman and his colleagues point out, “The benefits to society of delayed aging would accrue rapidly and would extend to all future generations.”

If delayed aging is worth that much, halting the march of the grim reaper entirely would be even more valuable. “Between 10 and 20 years from now it’s going to be a real revolution. I believe that we will overcome disease and aging,” the futurist Ray Kurzweil asserted in a talk at the Singularity University in October 2014. He added, “I believe that we are 10, 12, maybe 14 years away from where we will be adding more than a year of life expectancy every year, not just to infant life expectancy, but to your remaining life expectancy.”

Kurzweil calls this the “longevity escape velocity”: a scenario where technologies to stave off aging develop faster than people age. Back in 2005, the Harvard life extension researcher David Sinclair said he “would be disappointed if we were all born one generation too early.” Me too. Since 1960, average U.S. life expectancy has been increasing at a rate of two months for every year that has passed. That is utterly unsatisfactory.

The fiscal, social, and health dividends that achieving that feat would yield are effectively infinite.

Objections remain. Wouldn’t radically increased longevity lead to overpopulation, some wonder? In a 2013 article for the Public Policy & Aging Report, Olshansky uses realistic trend data to calculate that if everyone became immortal tomorrow, world population would take 80 years to double. Surely eight decades provides enough time for people to figure out how to adjust to immortality.

The prospect of eternal ennui concerns the environmentalist Bill McKibben. In his 2003 book Enough, he wrote, “The future stretches before you, endlessly flat.” But the future is “flat” only if you assume no progress. Who knows what prodigies of creativity will arise from people with decades of learning and the physical and mental energies of 30-year-olds? The plain fact is that social and technological innovation has been most rapid in those societies with the highest average life expectancies. The discoveries and possibilities in the coming centuries strike me as yielding a rather steep and exciting exponential knowledge and technology curve.

And if somehow lack of imagination did produce boredom, the solution is straightforward. You can experience the thrill of dying simply by stopping your longevity treatments.

Callahan, Emanuel, McKibben, and others who oppose anti-aging research have fallen for what the anti-aging advocate Aubrey de Grey calls the “Tithonus error”—the idea that extended life will necessarily mean extended frailty. They are suffering from a static way of thinking about the world they live in.

Researchers are in hot pursuit of promising treatments that would actually retard and maybe even reverse aging. Defusing fiscal time bombs would be only a minor consequence of deploying effective anti-aging treatments. Once rescued from the ravages of aging, all people will be endowed with the life and the liberty to truly pursue their happiness.