Longstanding questions about how the red-wine ingredient resveratrol works at the molecular level have been answered by Harvard’s David Sinclair and colleagues in a paper that just appeared in Science. The new research supports the idea that the compound directly activates an enzyme called SIRT1 to induce effects in cells that are similar to those caused by calorie restriction, which is known to slow aging in various species. You can read about my take on the new findings in this Scientific American blog.
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If you set out to learn a foreign language along with your kid, get ready for a provocative lesson about brain aging: At some point, you’re likely to find yourself falling ever farther behind, laboriously struggling to implant new words in your plainly decayed memory while your youngster absorbs them like animal crackers.
But the standard picture of one-way cognitive decline after about age 25 is way too simple, according to psychologists who study brain aging. In fact, their work suggests that cognitive development actually continues through middle age, and even beyond. The gist of this later development was nicely captured by the great Polish-American pianist Arthur Rubenstein, who continued to perform until he was pushing 90 (he died at 95): When asked at 80 how he managed to continue giving such good concerts, he explained that he relied on three strategems–he played fewer pieces, he practiced the pieces more often, and he used dramatically contrasting tempi to make it appear that he could play the piano faster than he actually could.
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Since 1935, scientists have known that putting rodents on very low calorie diets extends their lifespans. Scores of studies since then have shown that such calorie restriction (CR) can extend lifespan across species in a way suggesting it delays the onset of diseases of aging, extending healthspans (the proportion of life spent in good health) as well as lifespans. But, as detailed in my book, CR hasn’t extended lifespan in all species, nor has it worked in certain strains of rodents. In the latest study on the topic, it failed to extend lifespan in a long-term study in rhesus monkeys at the National Institute on Aging (NIA). The finding conflicts with results of another long-term CR study in rhesus monkeys at the Wisconsin National Primate Research Center in Madison, which showed that CR significantly improved late-life health in the primates; the Wisconsin study also offered evidence, though it wasn’t conclusive, that CR can extend lifespan in monkeys.
What all this means is that CR is probably more like medicine than magic. That is, almost all medicines work well for some individuals while doing little or nothing for others. Fewer than half of people put on antidepressants respond to them. And I can testify from personal experience that my genotype is virtually immune to Tylenol’s pain-killing effect.
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The first strong evidence that a drug could slow aging in mammals came out in 2009 when scientists reported that chronically feeding doses of rapamycin to mice significantly extended their average and maximum lifespans. Yet rapamycin, a drug used to help prevent rejection of transplanted organs, causes multiple side effects in people, including elevated triglycerides and cholesterol, increasing the risk of heart disease; moderate immune suppression, perhaps increasing infection risks; and low blood platelet levels, which raises the specter of dangerous bleeding. In recent years another especially surprising and troubling side effect has come to the fore: Chronically taking large doses of rapamycin induces “insulin insensitivity” in both rodents and humans, leading to rising blood sugar and potentially to type 2 diabetes.
How do we reconcile such adverse effects with the drug’s unprecedented ability to boost healthy aging and longevity, at least in mice?
Some telling insights on this burning issue were recently published in two reports on rapamycin’s effect on insulin and blood sugar: a mouse study that revealed a probable mechanism behind the effect and a theory paper suggesting that the purported diabetes risk has been overblown. Read More »
It’s not every day that scientists base a study on an idea behind the story of Peter Pan. But as the research showed, the notion that slow development goes with longer life—which in the immortal Peter’s case meant completely arrested development along with no aging—has implications that reach far beyond Neverland: Led by Rong Yuan at the Jackson Laboratory in Bar Harbor, Maine, the study has demonstrated a nifty new way to find genes that enhance longevity and healthy aging.
The hunt for such “gerontogenes” took off around 1990 when scientists discovered that mutations in certain roundworm genes could double their lifespans. A few years later, similar genes were found in mice, thanks partly to pioneering research at Jackson Laboratory led by two coauthors of the new study, Kevin Flurkey and David Harrison. The findings helped turn aging science into a hot field and raised hopes that drugs could be found that would mimic the effects of the mutations and thus slow human aging.
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Several people emailed me recently for my reaction to media stories on a University of Pittsburgh study in which the short lifespans of mice with a severe form of progeria (accelerated aging) were extended by injections of stem-cell-like muscle cells from young mice. So I took a look at the study and some related research, and here are some things that jumped out at me.
First, it has never been clear how much progerias can tell us about normal aging. Further, it’s not even clear which life-shortening syndromes to anoint as forms progeria, which implies that they have something to do with aging—there are a myriad degenerative diseases that shorten life and cause forms of bodily decay reminiscent of aging’s toll, and it’s a judgment call, sometimes rashly made, to label one of them a form of accelerated aging. Besides, no one knows whether 10% or 90% of the zillion forms of deterioration caused by aging, or something in between, must be present in a purported form of progeria in order for it to tell us truly interesting things about aging. As a general rule, I tend to think that progerias that kill very early in life, as does the one investigated in the Pittsburgh study (it’s called XFE progeroid syndrome, by the way, and it kills mice with a few weeks of birth), are usually less like normal aging than ones that work slower. Thus, I didn’t find the Pittsburgh study all that interesting at first glance—it seemed to be about a possible treatment for a rare congenital disease, not a study on aging.
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When I recently speculated that taking vitamin pills may contribute to unhealthy choices because many people assume the pills shield them from the choices’ ill effects, I figured there was no way to support my hunch. But I was mistaken: A recent Taiwanese study demonstrated that taking multivitamins does indeed make people feel protected against health hazards and thus more likely to indulge in unhealthy choices.
Led by Wen-Bin Chiou at National Sun Yat-Sen University, the researchers gave daily placebos for a week to 82 adults (45 women, 37 men, average age 31). They told half of the group that they were taking multivitamins, and at the end of the week administered surveys on the subjects’ health-related inclinations. The results: Those who thought they were taking vitamins reported a 44% higher tendency to partake in risky activities (examples included casual sex, sunbathing, and binge drinking), and a 61% higher preference for all-you-can-eat buffets over healthy meals, compared with those who knew they were taking placebos. The “multivitamin” group also reported exercising 14% less. The researchers concluded that multivitamin takers may experience an “illusory invulnerability” contributing to all kinds of risky behaviors.
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If you follow aging science—and my guess is that you’re one of those mortal, aging types who do—you might want to take a look at the latest issue of Scientific American (the January 2012 issue), which has a cover story I wrote for the magazine about research on target of rapamycin (TOR) and its implications for aging and finding ways to slow it down. Accompanying the article is a blog I wrote about how politics and faulty perceptions are preventing the huge practical promise of aging research from being realized, and why we should change that ASAP. There’s also a slide show about the very different rates of aging (and longevity) across mammals, and a piece on the extraordinary longevity of naked mole-rats, an adaptation of part of my book’s chapter on aging across species.
If you’ve tuned into the resveratrol story over the past five years, you’ve probably heard that you’d need to take giant doses of the red-wine ingredient to do any good. That idea was based on mouse studies in 2006 that showed massive doses of the compound blocked bad effects of eating too much fat. A front-page New York Times story on the studies, memorably headlined “Yes, Red Wine Holds Answer. Check Dosage,” conveyed the conventional wisdom at the time that “a 150-lb person would need to drink 750 to 1,500 bottles of red wine a day to get such a dose.”
Recent placebo-controlled clinical trials with resveratrol, however, suggest that much smaller doses—maybe a tenth as much as suggested by the Times‘ story—can have significant cardiac benefits. These smaller doses are still too large to get from drinking wine—you’d need to take resveratrol pills to equal them. But evidence is plainly growing that a rethink is in order.
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The negative buzz about sirtuins recently grew louder when Science ran a lengthy news piece on Dec. 2 titled, “Aging Genes: The Sirtuin Story Unravels.” The article played up studies in lower organisms casting doubt on earlier high-profile reports that sirtuin enzmes play major roles in aging, which in turn challenged the idea that they mediate health benefits linked to resveratrol, the famed red-wine ingredient. The most glaring of the skeptical reports, a British-led study that appeared in September in Nature, contradicted earlier studies that showed amping up a sirtuin called Sir2 in roundworms and fruit flies extends their lifespans. In the Science article, Linda Partridge, one of the British researchers, was quoted as saying that her team’s study “‘is basically a boring little story that says if you do the experiments properly,’ you arrive at the correct results.” This is pretty strong acid, no?
Partridge, along with editors of Science, apparently see the sirtuin story as an overfilled balloon begging to be popped. Joining in the fun, Nature‘s editors recently ran a headline—”Don’t write off sirtuins”—implying that they’re now in danger of being placed in the same category as a deadbeat’s IOU. But thanks to all the gleeful popping, we’re faced with a strange situation: The studies in yeast, worms and flies have totally upstaged a large, growing body of encouraging findings on sirtuins and resveratrol in mammals, including several small but revealing human clinical studies that recently appeared with little or no media notice. This situation is a first as far as I know when it comes to coverage of an important biomedical topic.
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No subject has inspired more hype and wishful thinking through the ages than life extension. Not surprisingly, our inner skeptics tend to counsel extreme caution when the talk turns to anti-aging elixirs. For many of us after a certain age, the skepticism is reinforced each morning with that first grimacing glance in the bathroom mirror, showing once again that no matter how many vitamins we've popped, cups of ginkgo tea we've downed, or miles we've jogged, we are melting, melting—oh, what a world!
But our mirrors are no longer sound counselors. Scientists have firmly established that the rate of aging is malleable, and now a well-founded quest for drugs that brake aging is rapidly unfolding. Peace, inner cynics: The compounds under study won't confer immortality. But they promise to usher in a new era of preventive medicine, one in which novel medicines arrive that can delay or avert just about everything that goes wrong with us as we age— dementia, cancer, osteoporosis, and, yes, jowls too—in the same way that medicines that lower blood pressure and cholesterol fend off heart disease today. That would change the practice of medicine, and our lives, more than any other biomedical advance on the horizon.
"Improvements in technology, particularly the ability to sequence DNA quickly, have made the serious study of ageing possible. All this is carefully chronicled in "The Youth Pill" by David Stipp, a former medical writer for the Wall Street Journal and an able guide to this young science. His book draws readers down the blind alleys and experimental dead ends that are an inevitable part of scientific research, as well as explaining the advances that have been made and the hunches that led to them."
"An engaging account of the burgeoning field dubbed gerontology-the study of aging and of medicinal tools to block its unwanted effects"
--Dr. Scott Gottlieb, former FDA deputy commissioner, Wall Street Journal
"The recent headway made in anti-ageing is exhilarating (and a little unsettling) in its implications. What Stipp shows is that the pursuit of endless youth is anything but a futile pipe dream; it is no longer a Wildean fantasy, but an imminent reality."
--The Financial Times
"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."
--Dr. Harriet Hall, Science-Based Medicine
"From the history of attitudes and philosophies on old age and various nostrums that have been pitched to the hard science of the cellular mechanisms of aging, genetic studies, and dietary variables and finally to what is becoming the big biotech business of life extension, Stipp covers the field admirably...This tour de force is recounted with insight, authority, and a somewhat breezy style reminiscent of the best of Natalie Angier's works."
--Gregg Sapp, Evergreen State College, Library Journal
"With wit, newsiness, and gingerly optimism Stipp leads the reader through laboratory assaults on the prime suspects of age-related decline: free radicals (and their nemeses, antioxidants); genes implicated in the aging process; telomeres (snippets of DNA that keep chromosomes from unraveling prematurely during cell division); and many more...a lively survey."
--Curt Suplee, AARP Magazine
"Stipp does a great job of explaining the scientific research and why it’s important with humorous qualifiers like “mom-wowing gerontogene discovery.”
--The Daily Beast
"Stipp's experiences as a popular Wall Street Journal and Fortune magazine writer have blessed him with a singular style, crafting complex explanations of scientific discoveries (and failures) into eminently enjoyable reading. Whether or not the notion of living energetically to the age of 150 appeals, Stipp makes the research compelling."
--Donna Chavez, Booklist
"...a well written and documented journey through all the theories, animal studies and human observations since the 1900's about the attempts to find the fountain of youth...Mr. Stipp delivers a detailed exploration of the complex quest for youth with humor and thoroughness. He entertains with details of intrigue and one-up-manship in the research world as well as everything you ever wanted to know about the naked mole-rat."
--Suzan M. Streichenwein, M.D., FAPM, Medical Front-Page