When I tell people about progress toward developing anti-aging drugs, they often come back at me with what I think of as the Struldbrugg question: “Won’t such drugs make lots of old people endlessly linger in a physically incapacitated or, worse, demented state?” (The Struldbruggs were a group of immortals in Gulliver’s Travels who aged without dying, becoming ever more miserably withered as time passed.) After all, many of us have witnessed our parents and grandparents outlive their parents only to wind up spending their final years slumped in wheelchairs along nursing-home corridors. It’s easy to believe that longer life tends to go with dragged-out misery at the end.
Fortunately, there are good reasons to think that anti-aging drugs would let us defy this pattern by both extending life and compressing late-life periods of morbidity. But before delving into that, let’s briefly review why so many people are living long enough to be afflicted by chronic diseases that earlier, shorter-lived generations had little experience with.
Life expectancy gains in the early 1900s largely stemmed from averting deaths from infections early in life. After 1950, further gains were achieved by averting premature deaths from diseases, primarily coronary heart disease, that often killed before age 70. Importantly, neither of these factors braked aging, which of course is what anti-aging drugs would do. And there’s no reason to think that the long-term effects of slowing down aging would resemble those, say, of vaccinating an infant against diphtheria or taking blood-pressure drugs at 55—while the latter increase life expectancy, they don’t oppose virtually everything that ails us as we get old, from Alzheimer’s to osteoporosis, as would anti-aging drugs.
This isn’t to say that such drugs would let us all live to a ripe old age in superb health and then suddenly pass away with no terminal decline. (This is the so-called one-hoss-shay effect, named after a poem by Oliver Wendell Holmes about a marvelously well-built carriage that lasted in great shape for a century and then “went to pieces all at once.”) I don’t expect the drugs to work miracles, totally eliminating late-life morbidity. But here’s the good news: All of the anti-aging interventions that have been shown so far to work in animals—including “gerontogene” mutations, calorie restriction, and drugs—appear, at worst, to postpone the onset of diseases of aging without lengthening their typical courses.
Merely delaying the pain of old age may not sound like a huge breakthrough. But if the percentage longevity gains seen in animals with slowed aging were replicated in humans, the resulting boost in life expectancy would greatly exceed that of curing all cancers or wiping out heart disease. Further, the fraction of our lives spent in late-life morbidity would be significantly reduced. As University of Michigan gerontologist Richard Miller points out, “When you ask people ‘would you like to live to 100?’ they picture what today’s elderly, infirm person looks and feels like. But the proper question is a different one: ‘Would you like to add another 10 or 20 years to the middle of your life, so you reach 80 or 90 in the same condition that people generally are today at around 60 or 70?’ The goal isn’t to prolong the survival of someone who is old and sick, but to postpone the period of being old and sick—not to produce a lot more standard-issue 100-year-olds, but to produce a brand new kind of 100-year-old person.”
While anti-aging drugs are unlikely to turn us into Struldbruggs, they may well make the total number of senior citizens grow significantly faster than expected. That would cause Medicare and other elderly entitlement-program costs to burgeon even as health-spans increase—the bottom line could be perilously large federal budget deficits and accumulated debt. Thus, it’s important to ask whether anti-aging drugs might actually compress periods of late-life morbidity in addition to delaying them. Such compression would reduce the average amount of time spent toward the end of life afflicted by disease, potentially yielding huge health-care cost savings that would offset rising entitlement-program expenses.
Unfortunately, little is known about anti-aging interventions’ effects on late-life morbidity and terminal decline—studies on such interventions in animals have been mainly concerned with life span not health span. Still, hints of compressed morbidity can be found in the anti-aging literature:
–In an ongoing study of calorie restriction’s effects in rhesus monkeys, age-related diseases have appeared in the calorie-restricted animals only about a third as often as they have in control animals. Having reached ages greater than the average life span of rhesus monkeys in captivity, the CR monkeys have greater lean muscle mass, significantly less age-related brain atrophy, and zero diabetes, as well as half as much cancer and cardiovascular disease as do peers on normal diets.
–When pathologists examine tissues of rodents on CR after death, they’ve found no visible signs of severe age-related diseases in a fourth to a third of the animals. This one-hoss-shay-like post-mortem finding is made in only about 6% of control animals.
–The slowest-aging rodents, naked mole-rats, whose striking longevity (nearly 30 years) represents a fascinating anti-aging experiment by evolution’s blind watchmaker, seldom show signs of chronic disease as they age in captivity. The African burrowers typically live nearly 10 times as long as similarly-sized rodents like mice and then suddenly die for no apparent reason.
–Mutations that delay aging in mice render them remarkably resistant to multiple diseases of aging, such as cataracts, detectable tumors and kidney disease. They also retain cognitive function later in life than do normal mice. Most revealing, nearly half of a strain of extra-long-lived dwarf mice, whose small size and up to 50% life-span extension stem from a defect growth-hormone signaling, die with no severe pathological lesions, compared with only about 10% of siblings with normal growth-hormone signaling and life spans.
–Smaller breeds of dogs, such as dachshunds and miniature poodles, are longer-lived than larger ones, such as Irish wolfhounds, probably because the former carry gene variants that slow aging. The smaller, slower-aging dogs have been found to suffer less cancer, locomotor disease, cardiac disease, and neurological disease at any adult age than do larger, faster-aging ones.
These suggestive data don’t prove anything, of course. And it’s entirely possible that anti-aging drugs will affect animals and humans differently. (I’ll take a look at human data on morbidity compression in a separate blog.) But I think they justify cautious optimism that such drugs would not only keep us healthier longer but also, in many cases, abbreviate late-life morbidity—just the opposite of the fate Jonathan Swift portrayed for the poor Struldbruggs.