In his new book The Youth Pill: Scientists at the Brink of an Anti-Aging Revolution, David Stipp tries to answer those questions. From the title of the book, I expected hype about resveratrol or some other miracle pill; but instead it is a nuanced, levelheaded, entertaining, informative account of the history and current state of longevity research. It makes that research come alive by telling stories about the people involved, the failures and setbacks, and the agonizingly slow process of teasing out the truth with a series of experiments that often seem to contradict each other.
Anti-aging can mean several things. Extending the average lifespan is not the same as extending the maximum life span. Extending lifespan is not the same as preventing the degenerative changes characteristic of aging.
We don’t even have a handle on why we die, why we deteriorate over time, or how it could benefit “selfish genes” for women to live past menopause. Several contradictory evolutionary explanations have been proposed. Comparisons with other species have not been helpful: every hypothesis has run up against counter-examples. Generally, the lifespan of animals correlates with body size; humans live longer for their size than expected. Some animals appear not to age. Naked mole rats are a fascinating anomaly: these animals that live in colonies underground and look like saber-toothed sausages live a long life for their size and appear not to show the usual changes of aging even though they have high levels of free radical damage and low levels of antioxidants (70 times less glutathione activity than mice).
Scientists hoped to find an aging gene that they could turn off. It’s not that simple. A large number of genes are involved in aging processes, and there are unpredictable interactions between them. Studying centenarians has provided inconsistent clues.
Antioxidants neutralize the free radicals that cause cell damage. They sounded promising, but their effect is modified by many factors, they can harm as well as help, and raising their levels with supplements may even turn off some of the body’s natural defenses.
Telomerase (the enzyme that keeps the ends of chromosomes from fraying as they age) was another false lead. Drugs that slow aging by boosting telomerase may cause cancer, and it turns out that telomere shortening isn’t the chief driver of body-wide aging.
The most promising idea is severe calorie restriction (CR). It prolongs life in several species, but this effect has not yet been verified in humans. And it is inconsistent and may have different effects at different ages and in different individuals. CR lowers body temperature and fertility and has other side effects. It is not an option most people would willingly choose.
Scientists have studied the chemical changes in CR humans and are looking for a pill that will cause those same changes while allowing people to eat unrestricted calories. Two main candidates have surfaced. Resveratrol (a substance found in red wine) seems to work: it allows overfed mice to live longer and stay healthier. It appears to have a number of benefits in lab animals, but human studies have not been done and it appears that very large doses will be required (comparable to the amount you would get by drinking 200 bottles of wine a day). Rapamycin extends the life of mice and prevents various diseases, but it also inhibits protein synthesis in the brain, suppresses immune function, and raises cholesterol. Researchers are trying to find related compounds that offer the benefits without the harms.
There are all too many variables that can interfere with the results of a study. In one experiment, the female mice lived longer with treatment but the males didn’t. They finally figured out that was because the males’ cagemates were killing them! Stipp does an excellent job of presenting the theoretical underpinnings, the experiments, and the difficulties of anti-aging research. The subject is overwhelmingly complicated, but he simplifies it enough to at least help the reader understand how very complicated it is.
There are longevity clinics and anti-aging products on the market offering all kinds of promises that go way beyond the knowledge. Futurist Ray Kurzweil takes handfuls of supplement pills and spends one day a week getting IVs and other treatments at a longevity clinic and he is convinced this regimen will keep him alive until science finds a way to keep him alive forever. The author of The Youth Pill is more conservative. He is enthusiastic about the promising research on pills like resveratrol and rapamycin, but he’s reluctant to start taking them “until enough clinical data are available to let me make a reasonably well-informed decision about optimal dosing.” Me too.
This article was originally published in the Science-Based Medicine Blog.