The Youth Pill

As gerontologists are fond of pointing out, the word aging doesn’t necessarily refer to the physical deterioration we usually associate with it—consider the aging of wine—and some of them insist on using the term senescence instead to refer to the process that turns us from springy youths into frail seniors. I’ll stick with aging.

Contrary to the assertions of some who would “cure” it with their favorite elixirs, aging isn’t a disease. Diseases afflict subsets of the population; aging hits everybody. And it would be counterintuitive, even semantically reckless, to assert that a person at fifty is sick because he’s less adept at learning to play a musical instrument or at turning cart-wheels than he was at twenty—Michael Jordan didn’t retire from the NBA because he was ill. Of course, there’s a close link between aging and sickness—some scientists define aging as a bodily process that increases vulnerability to disease.

While popping antioxidant pills has come under fire in the medical literature, there are still good arguments for taking multivitamins that contain modest amounts of antioxidant vitamins. Distinguished biochemist Bruce Ames, for example, argues that excessive consumption of nutrient-poor refined foods leaves many people in today’s world with inadequate intake of a number of vitamins and minerals, possibly boosting the risks of cancer, neural decay, and accelerated aging.

Genes located near one another on DNA molecules tend to be inherited together. Thus, if abnormally long life in worms were usually inherited along with a trait whose gene location is known, say, infertility, scientists would know that the long-life gene, or genes, is near the fertility-related one. By repeatedly using this fellow-traveler principle with previously mapped genes, they could get an increasingly precise fix on the long-life gene’s location in the genome.

Once I asked Johnson whether he resented the fact that his pioneering work on anti-aging genes has received far less notice than Kenyon’s has. It didn’t seem to bother him much. In fact, he mildly observed, the validity of his age-1 discovery was widely doubted until Kenyon reported her similar finding, and thus he had felt more buoyed than deflated by the buzz about daf-2.

My favorite recipe for successful aging was devised by famed African American pitcher Satchel Paige: “Avoid fried meats which angry up the blood. If your stomach antagonizes you, pacify it with cool thoughts. Keep the juices flowing by jangling around gently as you move. Go very lightly on the vices, such as carrying on in society, as the social ramble ain’t restful. Avoid running at all times. Don’t look back, something might be gaining on you.”

Various studies have indicated that CR’s anti-aging effects in rodents stem from lowered intake of calories rather than of other dietary components. But there’s evidence that reduced intake of methionine, an amino acid found in meat, fish, nuts, and many other foods, also extends rodents’ life spans. While methionine-restricted diets may offer significant health benefits to people, little is known about their pros and cons, and they are difficult for humans to undertake because methionine is found in so many foods.

A similar analogy gerontologists often trot out when discussing compressed morbidity is the “one-hoss shay,” a fictitious carriage described in a poem by Oliver Wendell Holmes Sr. Thanks to the fact that each of its high-quality parts was equally strong, it suddenly “went to pieces all at once” after lasting exactly one hundred years.

Telomeres’ role in aging still isn’t clear, though. In 2008 Spanish scientists reported that mice with artificially revved up telomerase showed signs of retarded aging. (The enhanced rodents also had to be implanted with cancer-blocking genes, because boosting telomerase normally causes tumors.) And in late 2009 a group at the Albert Einstein College of Medicine reported that some centenarians carry variants of the telomerase gene that appear to enhance longevity by keeping telomeres in good shape.

Some other gerontologists I know did such things as youths. For instance, Steve Austad, the former lion trainer from chapter 3, told me that at age eleven he also liked to shoot arrows straight up. He and his pals did it at night, however, and didn’t run for cover—they wanted to get the thrill of hearing the thwack of returning arrows hitting nearby. No one got hit that way, but his archery adventures ended after they switched to playing bow-and-arrow dodgeball and he wound up with an arrow buried in his thigh—that was difficult to explain to his parents, he said.

Resveratrol is a natural molecule that can’t be patented. Sirtris did seek to patent SRT501’s special formulation of resveratrol, which reportedly delivers four times as much of the compound into the bloodstream as do widely sold supplements, based on comparable doses. But such patents are relatively easy to circumvent. Thus, SRT501 was of limited value to Sirtris as a bargaining chip in negotiations with big pharma.

As the abysmally low success rate in drug development shows, it’s incredibly difficult to make even relatively minor adjustments in the operation of living systems. Thus, I feel that engineering the far more profound, complex changes needed for negligible senescence—even if we knew precisely what changes were required, which we don’t—is about as likely to happen during, say, the next fifty years as the bioengineering of a little Dutch boy with hundreds of arms and thousands of fingers. Still, I admire de Grey’s spirited, detail-oriented optimism, and I find his speculations about how we might someday arrest bodily decay, detailed in his 2007 book Ending Aging, quite intriguing—no other far-out anti-aging dreamer has as many interesting things to say as he does.

A few studies suggest that being overweight doesn’t raise the risk of fatal diseases and may actually protect against them. But I think they’re misleading. Importantly, they’re based on subjects’ BMI at single points in time, often late in life, rather than cumulative lifetime exposure to the deleterious effects of visceral fat—the kind that lards up the liver and other organs in potbellied persons—which is very likely what matters. And they may lowball overweight’s health fallout due to inclusion of people with chronic undiagnosed diseases, especially smoking-related lung conditions that play out over many years. Such people often are thin yet die young, effectively making the thin side of the weight spectrum seem riskier, and the fat side seem less risky, for reasons that have nothing to do with weight.

I’m aware of only one recent clinical trial of anti-aging effects: DSM Nutritional Products, a vitamin seller based in the Netherlands, has sponsored a small, exploratory clinical trial of resveratrol pills’ ability to induce gene-activity changes in muscle like those caused by CR. Insulin sensitivity and other biomarkers affected by CR were also assessed. Conducted at Washington University School of Medicine in St. Louis, the three-month, placebo-controlled trial employed modest doses of resveratrol, 75 milligrams a day. The results haven’t been disclosed at this writing.