Can We Live Longer but Stay Younger?

There are many skeptics among scientists who wonder how much, or how soon, this kind of work will really affect aging. Church gets shares for serving on the advisory board of Elysium Health, which markets an anti-aging supplement called Basis, and though the literature is careful to say that, “rather than endorsing a specific product, this network of scientists, clinicians and health professionals advises the Elysium team on product identification and development,” how one distinguishes between advising on the product and endorsing the product seems to many a bit mystical. Others may recall the enthusiasm, in the early twentieth century, for implanting monkey glands in people, a procedure that was held out as a scientific solution to the problem of aging. (W. B. Yeats had a related procedure.) The fountain of youth is always splashing away somewhere.

Behind the optimistic promise of heading off aging in spaniels and, soon, in their owners lies a sadder reality: that even foundational research cannot always cure a fundamental problem. Despite what had seemed to be groundbreaking discoveries in the basic genetics and pathology of dementia, no cure or even promising treatment for senility, as it once was called, is in sight. Increasing numbers of people enter old age not merely reduced but ravaged by Alzheimer’s or another form of dementia, now epidemic in the richer countries that have greater life expectancies. Old Lear’s primary fear is not of age but of madness, which he imagines precisely as dementia: as the loss of mental control, of memory, and of cognition, seeing his fate mirrored in that of Poor Tom, the ranting homeless man impersonated by Edgar.

To pass from the Harvard rejuvenators to the laboratory of Patrick Hof, at the Icahn School of Medicine at Mount Sinai, in Manhattan, is to sober up a little. Here, there is talk not of imminent innovation but of discouragingly minute work proceeding on many slow-moving fronts over decades. Where the Harvard crowd see quick fixes in the near future, Hof, an expert on the neuronal underpinnings of aging and Alzheimer’s, sees the exposure of ever more confounding complexity.

His tenth-floor office is filled with reproductions of Blake illuminations and Whistler portraits, while photographs of his children cycle on the screen saver behind him, blended with images of whales and dolphins, a particular interest of his. His nearby lab is an open space with small chapels off it, in which researchers—postdocs, junior faculty, skilled technicians—study the youthful and aged brains of many kinds of animals, with what looks like every kind of microscope: smaller viewing ones, mid-sized high-resolution ones, and a single massive electron-scanning microscope that lets his researchers see neural structure down to a dendrite’s tiny terminal spines.

“My career started at the beginning of digital microscopy,” Hof says. He is white-haired, with the soft accent of his native Switzerland. “Now we can collect terabytes of data—we can collect entire networks of neurons within a single animal brain. We do tissue staining, taking a piece of brain or an entire brain—slicing them into very thin sections, which we incubate with an antibody that labels a specific population of neurons, and we collect that. Or we can load neurons with a fluorescent dye—inject it, using a very thin glass pipette that runs right into the neuron—so then we have a fluorescent neuron!”

Hof’s laboratory is full of brains. In a large common lab outside the microscopy rooms, there are shelves holding rows of what look like hinged, dark-wooden cigar boxes. “These are all brains,” Hof says casually. He takes a box down and opens it; inside, there’s a slide with what looks like a small profile of a brain on it. “That’s a human brain. It’s a section, sliced like bread. It looks small, because it was incubated in a chemical process—we started with the entire hemisphere and then incubated it in an alcoholic treatment, and it shrinks by two-thirds. Then you stain it, and there you go.” The brain sections are kept indefinitely, Hof explains, and loaned out, like library books, from lab to lab.

Hof, who has taken to studying the brains of whales and dolphins, likes to bring visitors to an open, chilled “brain room,” a sort of rare-book collection of brains, to see a few beautiful instances. The brain room is a revelation. Here they are: human brains, monkey brains, dolphin brains—the space between brain and mind never seems so large as it does when you actually see the material of mind, curved and segmented, as ugly as an intestine, floating in a fixing solution.

The room even contains a sperm-whale brain—“the largest brain known to the planet,” Hof says. (It looks beautifully broad, with nobly large-spaced convolutions.) Finding the brains of senile cetaceans is hard, he says. “The ones that beach are young adults, and the seniors tend to die quietly at sea.” Hof hopes that insight might be found in studying neurodegeneration in the cetaceans’ more expansive, differently structured cortexes.

The study of Alzheimer’s became Hof’s special preoccupation because of its insidious destruction of normal minds and normal character. “You can’t tell any difference, even under extreme magnification, between an aging non-demented brain and a younger human one,” he says. “You have to have really fine levels of resolution to see any loss in neural organization just through aging without illness. But, holding an Alzheimer’s brain in your hand, you can see the atrophy.”

Three decades ago, Hof explains, research in Alzheimer’s linked two key proteins with the terrible dissolution of selves: beta-amyloid, which formed plaques between neurons; and tau, which formed tangled fibrils within neurons. The relative importance of the two was disputed, but many scientists concluded that those plaques and fibrils clog the brain as coffee grounds clog a drain. It seemed likely that there would be therapeutic benefits if they could be cleared away. “Now, we know that these are really downstream effects,” Hof says. “What’s happening upstream to cause them is much, much more complicated.”

With the causes unclear—debate continues over which anomalies are better seen as culprits or as bystanders—and the cure evidently far away, Hof can only enumerate the “co-morbidities” for Alzheimer’s, the conditions that correlate most strongly with its onset. They are the old-fashioned sins: obesity, a lack of exercise, bad diet—and the diabetes that these can produce. For all the cascades of research into longevity, the new science often seems to distill into old wisdom: be fit, stay thin, and you will look and feel younger longer.

“The disease is diverse and heterogeneous enough that treatment and prevention will have to move on several fronts,” Hof says. “First, just promoting healthy aging, what can you do and what can you avoid? Every elder is unique, and will have had life experiences and habits that are unique. So we’re going to have to look at that aspect, in ways that prevent or treat, to a degree, the development of something worse. Then we need to have a better understanding of the causative factors. There are leads that point to a number of interesting markers. There are proteins that play cellular roles that effect a cascade of reaction inside the cells, but it becomes very difficult to target specifically without altering other functions. None of it is easy.”

As you take off the agnes suit—piece by piece; the boots and then the wrist weights and the impeding gloves—the feeling is disconcerting. It’s the return of flow, the feeling of choice and possibility as you begin to move again through the world, that makes you recall that what it is to be young is not to be in a state of ecstasy but merely to be unimpeded, to be in the world without having undue consciousness of your own muscle and bone within it. It’s the same thing we experience when we remove a splinter from our foot; what we get is not happiness in a positive sense but a return to not having to think about the prison and the fact of our flesh. We forget our insides, and fold ourselves back out.

The true condition of youth is the physical ability to forget ourselves. A friend who is still creative in his eighties points out what he calls the geriatric possessive: people past eighty, he says, are expected to say, “I’m going to take my bath,” “I’m going to take my walk.” We can counterpoise that to the pediatric possessive: “You’re going to take your bath,” “It’s time for your nap.” Only in midlife do we feel secure enough to enumerate actions as existing individually outside our possession of them: “I’m going to take a bath,” “I’m going to take a nap.” A bath and a nap exist, briefly, outside our possession of them—they’re just around for the taking, we suppose, and always will be.

Glenda Jackson, now playing Lear on Broadway at the age of eighty-three, captures the indomitable egotism of the aged. Watching her onstage, we are asked to recognize not just the anger but also, eventually, the wisdom of age. The old, Shakespeare says, can become, or assist us to become, God’s spies. A decade and a half ago, a Presidential council chaired by the bioethicist Leon Kass produced a report raising questions about research into extended longevity. “Might we be cheating ourselves,” the report asked, “by departing from the contour and constraint of natural life (our frailty and finitude) which serve as a lens for a larger vision that might give all of life coherence and sustaining significance?” We do turn, after all, to the imagery of the old for comfort; we turn to work marked by the frailties of aging for consolation and enlightenment. Matisse, his hands crippled by arthritis, picks up scissors and painted paper and finds a new world of purity; de Kooning, on the edge of Alzheimer’s, paints some of his greatest pictures just as renewed simplicity breaks the hand of excessive excellence.

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