Human development is gorgeous, Jonathan Weiner writes in Long for the World: The Strange Science of Immortality. The union of sperm and egg results in precise, pre-ordained splitting and budding, creating something predictable yet wholly unique. Human aging is a mess. Our cells break down in a chaotic fashion, and mutation piles upon mutation. Our organs and bones seem to decompose while we still depend on them. It's a cascading decline leading to our inevitable death.
We age because nature loses interest in us, Weiner argues in his new book, an investigation into our ugly endings and what science can do about this disorderly process. He embraces the widely accepted theory postulated by the Nobel Prize winning zoologist, the late Peter Medawar, that evolution's push is to get us up and reproducing. So, for example, we need calcium to help solidify our young bones. But once we're sturdy enough to grab a mate and pass on our genes, we've done our work. Nature doesn't care if some of the calcium then hardens our arteries, causing late-in-life heart attacks.
We care, however, and David Stipp in The Youth Pill: Scientists at the Brink of an Anti-Aging Revolution joins Weiner in exploring the frontiers of the science that is tackling the possibilities of beating aging and cheating death. Weiner brings a lyrical, even meditative, approach to his portraits of the people who are at work tweaking the evolutionary process. Stipp has the workmanlike doggedness of a business reporter as he tracks a field that has migrated from the medical margins toward the scientific mainstream over the past 40 years. Both left me certain that the science of longevity is going to empty neither hospitals nor mortuaries within any of our lifetimes.
Against those who might argue that the last thing we need is yet more old people sucking up resources, the researchers counter that aged populations are a global fact and their goal is to keep people healthy for as long as possible, a benefit not only to each old person, but to society. The surge in the elderly as an age group certainly is impressive. At the beginning of the 20th century, a baby born in the developed world had an average life expectancy of less than 50 years. As the century progressed, advances in public health, widespread vaccination, and the introduction of antibiotics sent infant mortality rates plummeting, which gave more people the chance to get old. By the end of the 20th century, a baby born in the developed world could expect to live to around 80. As Weiner writes, this 30-year addition in life expectancy was "as much time as our species had gained before in the whole struggle of existence." (The outer limit of the human lifespan remains at around 120 years; only a handful have gotten close to this milestone.)
The good news is that more of us are striding, not tottering, into old age, which could be the result of our healthier childhoods. Weiner cites the theory that fewer childhood infections mean we experience less chronic inflammation, an engine of disease. Even so, if we live long enough, eventually for most of us a myriad of possible miseries await, from neurodegenerative diseases like Alzheimer's and Parkinson's to long-simmering but sudden killers like heart attacks and strokes to the runaway frenzy of cancer.
The researchers profiled by Stipp are seeking to master the mechanisms of our decline, so that we can frolic vigorously for eight or nine decades before dying in a brief and efficient fashion. Weiner's muse is prophet, maverick, and crank Aubrey de Grey of Cambridge University, whose vision is more ambitious. A theoretician in the gerontology field, he challenges bench scientists to come up with the necessary biological fixes so humans can reach something close to immortality.
Either quest is a tall one. Both Weiner and Stipp describe the difficulties of establishing scientific credibility in a field that has a disreputable, even ignominious past. In the early 20th century, one rejuvenator transplanted ape testicles into men. Another, Eugen Steinach, performed vasectomies as a way to restore flagging virility. Sigmund Freud is said to have been "Steinached," as was William Butler Yeats—a snip for that "tattered coat upon a stick." In that era, the fix for female revitalization was irradiating the ovaries.
But by the 1970s a handful of serious scientists had begun studying other species' lifespans, with methods that ranged from documenting them in the wild to selectively breeding lab animals to identify longevity genes. "Comparative gerontology" looks at the amazingly diverse aging styles in the animal kingdom. Fruit flies live weeks; the quahog can live four centuries. Mice and rats live only a few years, even in the cosseted safety of the laboratory, getting scruffy and sluggish in the process. It's another rodent that entrances researchers of longevity. The naked mole rat spends decades digging burrows while barely showing any sign of age (scientists call this "negligible senescence") until dropping dead of unknown causes. If only we could get old like naked mole rats, the cosmetic rejuvenation industry would go out of business.
Of course, extrapolating from animals to humans is always a big leap, but almost three-quarters of a century ago, once-forgotten research on the life-lengthening effects of manipulating animals' environment turned up something provocative. In the 1930s, a nutrition researcher at Cornell, Clive McCay, did a four-year study which demonstrated that putting rats on a near-starvation diet enhances their health and vastly extends their life. This was, Stipp writes, an astounding, heretical finding: "McCay showed that the rate of aging is incredibly plastic, and that it's supremely simple to brake it in animals whose inner workings aren't all that different from ours."
For decades McCay's discovery was neglected. But in recent years, calorie restriction (CR) has become the basis for one of the hottest areas of life extension research. Across many species, evidently including monkeys, being hungry stimulates resistance to cancer, neurodegeneration, and immune disorders. Stipp says the secret to the long lives of Okinawans—their number of centenarians per capita sets the world record—may lie in their sparing consumption of the traditional Japanese diet of mostly vegetables and fish.
The obvious problem with applying this finding in the developed world is that people with access to unlimited food find it hard to get through a single day on CR. So researchers are looking for CR "mimetics"—that is, drugs that would allow us to sate ourselves while triggering the molecular pathways that make being hungry such a good way to stay young. It's the pharmacological version of having your cake and eating it, too.
The underlying mechanisms that make us age remain a matter of speculation. De Grey champions an increasingly accepted view in the field of aging that the overarching cause of our decline lies in what some scientists call "the garbage catastrophe." As Weiner deftly explains the theory, it has instinctive appeal to any homeowner. The idea is that on the cellular level things start breaking down, and junk and gunk accumulate, overwhelming the mechanisms that are supposed to keep our cells humming. Researchers who study what actually are called "housekeeping" genes—which rid cells of the detritus—complain their important work is considered marginal and unglamorous. De Grey hopes their discoveries could lead to what will be a kind of molecular solvent to get rid of the crud—but it is a colossal "could."
Which brings us to the "youth pill" of Stipp's title and the ongoing search for a life-extending pharmaceutical that would keep us young by mimicking the effects of CR and keeping our cellular cleaning crew on duty. Stipp gives a lengthy account of the travails of Sirtris Pharmaceuticals, the company that hopes to package some form of the recently discovered class of enzymes called sirtuins. It's thought they protect cells from damage to the DNA and repair those mutations that happen. (Resveratrol, a substance found in red wine, apparently activates sirtuins in the body.) Then he introduces rapamycin, an immune suppressant drug used in transplant patients, which has shown a life-extending effect in lab animals. As I slogged on, ever more convinced that Sirtris was not going to find the solution to our mortal dilemma, Stipp's book began to resemble the process of aging itself: clogged with unnecessary information that should have been swept away.
Weiner, who has a gift for making science lucid and for weaving in the perfect literary allusion, is a pleasure to read. But he, too, slows down toward the close. His book ends with a lengthy philosophical meditation on the meaning of immortality, which his previous chapters failed to convince me is a subject worth spending too much of one's limited time worrying over. Not even Weiner buys Aubrey de Grey's vision of a human lifespan of hundreds, even thousands of years.
I did come away convinced to keep drinking coffee and indulging judiciously in red wine and dark chocolate. These foodstuffs have small amounts of the chemicals that may activate natural anti-aging pathways. And even if they don't send me to what De Grey calls "escape velocity," they make what time I do have more pleasurable.