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Scientists Make Headway Against Alzheimer’s–In Mice

31 Jul

Leonard Guarente

According to a paper published in the journal Cell, leading aging researcher Leonard Guarente has shown that activating a protein called SIRT1 appears to treat Alzheimer’s in mice. Guarente is on the scientific advisory board of Sirtris Pharmaceuticals, a company that has been studying SIRT1 and other proteins known as sirtuins, which its scientists believe are important in the aging process. Sirtris was bought by drug giant GlaxoSmithKline for $720 million in 2008.

Guarente’s research showed that increasing the level of SIRT1 in the brains of mice lowered the production of beta-amyloid plaques–fragments that build up in the brain and are believed to cause memory loss and other symptoms of Alzheimer’s.

Not surprisingly, the finding garnered some skepticism. Dr. Howard Fillit, executive director of the Alzheimer’s Drug Discovery Foundation, pointed out to the Boston Globe that Alzheimer’s has been cured over 150 times in mice–but never in people. Even the scientists engaged in sirtuin research caution that their findings might not translate into therapies for humans.

Nevertheless, this sort of news will likely boost demand for resveratrol, the red wine supplement that many natural-health enthusiasts believe can extend life. Enthusiasm for resveratrol was sparked by Sirtris co-founder and Harvard scientist David Sinclair, who first proposed the idea that the natural compound might activate sirtuins and extend life.

Since then, Sirtris and Glaxo have moved on to study much more potent sirtuin activators. And Sinclair has pointed out many times that you’d have to drink an awful lot of red wine–or gobble down many bottles of resveratrol supplements–to get any benefit.

That hasn’t stopped the supplement industry from capitalizing on resveratrol fever, though. According to Nutrition Business Journal, media hype generated $30 million in resveratrol sales in 2008, and many supplement sellers are forecasting 100% increases in demand each year. This despite the fact that resveratrol has never been shown to have any therapeutic effect in humans.

And now we have this Alzheimer’s development. Can you hear the cash registers ringing at your local health food store?

 
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On 100-year-old salamanders–and People

26 Jul

Two very interesting aging-related news items came across my desk this week. The first is a blog entry in Science on the discovery of a type of cave-dwelling salamander that lives to be 100. It’s called an olm, it’s about 15 grams, and it lives in caves throughout Europe.

Why does it live so long? Scientists are stumped. It has no natural predators, which helps, but it lacks some of the traits that other long-lived animals have. For example, it doesn’t have the naturally protective benefits of being large (like an elephant) or of having a low metabolic rate. It’s not immune to oxidative stress, which is thought to contribute to aging. The scientists plan to study the olm, in the hopes of unlocking the secrets to extreme aging.

Meanwhile a gerontologist named Robert Young, who works for Guinness World Records, has made it his job to track people who live to 100 and beyond. According to his records, the oldest living human is Eugenie Blanchard of the French territory of Saint Barthelemy. (WSJ subscription may be required to read more.)

Surprisingly, the number of centenarians has grown 32% in the past five years, while the number of “super-centenarians”–those who live to 110–has stayed flat. No one is quite sure why that is. But perhaps the salamander will someday provide clues into how the rest of us can achieve the rare milestone of 100-plus.

 
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Studies Question Andropause and Testosterone Replacement

24 Jul

Male menopause, or andropause, is one of the anti-aging industry’s favorite diagnoses. Is your energy level wanting? Is your sex drive waning? Are your muscles not as bulky as they used to be? Perhaps it’s time for some testosterone gel–or so the sales pitch goes.

But some studies question the wisdom of prescribing testosterone to aging men. Most recently, the prestigious New England Journal of Medicine published a study questioning the safety of testosterone replacement. During the study, which was sponsored by the National Institute on Aging, testosterone was prescribed to several men with limited mobility, in the hopes it would improve their ability to get around.

Unexpected side effects brought the trial to a screeching halt, though. The men receiving the gel suffered higher rates of cardiac, respiratory and skin reactions than did those getting a placebo. And 23 men on testosterone gel had adverse cardiovascular events, as opposed to only five in the placebo group. The researchers stopped the trial earlier than planned.

Until recently, there had been precious little research on testosterone replacement in aging men. Despite the alarm bells raised by this study, researchers are powering ahead; The NIA is planning a trial with 800 men, and the National Academies’ Institute of Medicine is also looking into testosterone research.

But as I found while researching Selling the Fountain of Youth, there is some compelling research questioning whether men who think they’re suffering from male menopause really have low testosterone. In 2006, scientists at the University of Turku in Finland set out to treat 200 healthy aging men with testosterone and track their results. They sent questionnaires to 30,000 men–1,800 of whom reported common symptoms of male menopause.

As it turns out, only 250 of them had low testosterone as it would be defined by traditional doctors. And most of those men suffered from other diseases–which disqualified them from a study designed to look at healthy men. The scientists pulled the plug on the study.

“Our finding begs the question, is there such a thing as andropause in men with no diseases, who are living a normal life?” said lead investigator Antti Perheentupa in an interview with me. “Is there any reason to treat healthy men with testosterone at all? The answer is probably no.”

 
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To Age or Not to Age? New Documentary Argues Latter

17 Jul

Bangor University

Last night I ventured to Greenwich Village for a screening of the new documentary To Age or Not To Age? It was followed by a Q&A with its director, Robert Kane Pappas. The film features some of the most famous scientists in the field of aging, including Leonard Guarante and Cynthia Kenyon, who have both made groundbreaking discoveries about the genes involved in the aging process. Sirtris Pharmaceuticals co-founder David Sinclair, who I write about in Selling the Fountain of Youth, also figures prominently in this film. He’s the Harvard professor who’s studying the potential life-extending powers of the red-wine extract known as resveratrol.

Though the movie amounts to little more than talking scientists–mixed in with a few aging people musing about immortality–it’s quite clear to me what Pappas’ answer to the question posed in his title is. He seems to fully support the notion that anti-aging research might result in a pill we could all take someday to avoid aging. The scientists who appear in the film are built up as heroes, complete with dramatic music to accompany their interviews. All of them spout plenty of caveats about how difficult it will be to translate their discoveries into therapies. Nevertheless, when Pappas introduced himself to the 25 or so viewers who showed up for the screening, he began by declaring anti-aging research to be “very very hopeful.”

Audience members bombarded Pappas with questions about resveratrol in particular. The extract is widely available as a nutritional supplement, though Sirtris is studying far more potent versions of it. And the company and its corporate partner, GlaxoSmithKline, aren’t pursuing it as a cure for aging, but rather for age-related diseases such as diabetes. Still, some audience members were clearly eager to try it. “Should I take one or two?” a viewer asked Pappas. The filmmaker pointed out that David Sinclair himself has professed to taking resveratrol. True, but Sinclair is the first to admit that resveratrol has not been scientifically proven to extend life or cure disease. And when some Web-based sellers of resveratrol supplements started using Sinclair’s name and likeness without his permission to sell their products, he was none too happy about it.

To Age or Not to Age raises many more questions than it answered. It features, for example, a 400-year-old clam that was discovered a few years back in Iceland and is now being studied by scientists in Wales. But how do they know it’s 400 years old? And how are they unlocking the secrets to the clam’s extraordinarily long life? The film doesn’t say. I did some Googling and at least found the answer to the first question. Turns out clams have lines on their shells–sort of like tree rings–that reveal their age. This clam was indeed alive when Shakespeare was writing his masterpieces. Question is, will any of us still be alive when he reveals the clues to his immortality?

 
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Global Aging Crisis? New Scientific Group Urges Action

15 Jul

A group of scientists recently gathered in California to discuss what they view as a global catastrophe. The aged will soon vastly outnumber the young, declared the group, which met at the behest of Lifestar Institute. But their vulnerability to age-related diseases will create a double-whammy for the economy: It will take productive folks out of the workplace, while at the same time taxing our already over-burdened health care system.

Few would argue with this theory. But the group’s plan for solving the problem might raise some eyebrows. They are calling for governments and life-sciences companies to fund three initiatives: Educating the public about how lifestyle choices can extend life; developing medicines to combat aging; and inventing regenerative technologies–i.e. stem cell therapies–for restoring parts of the body that decay with age.

I definitely applaud the first idea on their list. As I write in Selling the Fountain of Youth and in a previous post here, making good diet and exercise choices seems to extend life. Of course, getting people to eat well and exercise is not so easy–most people would rather be able to pop a pill to gain the same benefits.

Which brings us to the second idea–and one that’s a bit more questionable. The U.S. Food & Drug Administration doesn’t recognize aging as a disease. So pharmaceutical companies are much more likely to develop products to address diseases of aging–such as cancer and diabetes–rather than trying to prove those drugs actually fend off old age. Judging from a paper they published in the July 14 issue of the journal Science Translational Medicine, LifeStar and its panel of scientists believe this should change. They argue the industry should make medicines that repair and prevent the ravages of age. But without the support of regulators, their idea is unlikely to gain much traction.

As for regenerative medicine, it has a long way to go. Stem cell research is booming, especially in states like California, where it’s fueled by $3 billion in funding. But the day when we’ll be able to grow, say, a replacement kidney from a patient’s own stem cells is still the stuff of science fiction. So for now, we’ll just have to settle for organizations like LifeStar promoting the fantasy.

 
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Scientists Discover Genetic Cues for Longevity: Let the Hype Begin!

01 Jul

Today the prestigious journal Science released a paper identifying genetic factors that can predict–with 77 percent accuracy–who will live an exceptionally long life. Not surprisingly, the study garnered a ton of interest: I Googled it about 15 minutes after it was released and found a dozen or so articles already zooming across the Internet, disseminated by a number of major news outlets.

The research is tantalizing, to say the least. A team of scientists at Boston University discovered 150 genetic variants known as single nucleotide polymorphisms (SNPs) that they believe can predict who will survive into their late 90s and beyond. They also discovered 19 clusters of genes that seem to correlate with the onset and prevalence of age-related diseases such as dementia. This is the type of news anti-aging proponents drool over: It raises the possibility of developing products that can be used to predict age-related diseases long before they strike, and to sell drugs and other products that purport to prevent such illnesses.

The scientists responsible for this discovery are in no way encouraging such commerce. During a call with reporters, lead researcher and geriatrician Thomas Perls said it would be conceivable to “produce a chip that would help predict people’s genetic predisposition for exceptional longevity.” But he was quick to add a caveat: “All the authors of this paper want to instill a great deal of caution in thinking about what people might actually do with that information. Will that stop companies from going ahead and doing this? Probably not.”

Perls is well familiar with the lengths the anti-aging industry will take to sell youth. He has been an outspoken opponent of the anti-aging industry’s use of human growth hormone, much to the chagrin of the industry. He’s a pivotal character in my book, and an often-quoted expert on what doesn’t work when it comes to staving off old age. He should know: He is the director of BU’s New England Centenarian Study–an ongoing project involving 1,600 people over the age of 100.

In fact, much of the data behind this discovery came from the Centenarian Study, which began in 1995. Perls and his colleagues already knew that 90% of centenarians were still exceptionally healthy at the average age of 93. “So they very much compress their diseases or disabilities towards the very end of their lives,” he said. The team screened 300,000 SNPs across the genome in order to identify the ones most pivotal to longevity.

Still, science isn’t anywhere near being able to predict how long any of us will live. And there are so many factors beyond our genetic destiny that come into play. Perls himself said it best: “I think that we’re quite a ways away still in understanding what pathways governed by these genes are involved and how the integration of these genes–not just with themselves but with environmental factors–are all playing a role in this longevity puzzle.”

 
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Will There Ever Be a Youth Pill?

24 Jun

An article in the July/August issue of Technology Review recounts the travails of Sirtris Pharmaceuticals, a company founded on the premise that resveratrol–a substance in red wine–might extend life. Resveratrol seemed in early research to activate an enzyme known as a sirtuin, which in turn mimicked the life-extending impact of calorie restriction. The writer, Karen Weintraub (no relation), reveals some recent events that have taken the shine off Sirtris’ approach, raising doubts that a so-called “youth pill” is anywhere on the horizon. The story is pegged to the release of the book The Youth Pill, by former Fortune writer David Stipp.

I also write about Sirtris in Selling the Fountain of Youth, but with a decidedly skeptical take. Long before Sirtris had any compelling scientific proof its approach worked, entrepreneurs started selling resveratrol supplements and claiming that one of Sirtris’ co-founders, Harvard scientist David Sinclair, was actually endorsing them (he wasn’t). Still, Sinclair became a media darling, appearing as an anti-aging expert on 60 Minutes, and sharing a bottle of red wine with a coy Barbara Walters on a TV special called “Live to be 150…Can You Do It?”

Sinclair knows full well the science will take a long time to come to fruition, and he has said many times–including in interviews I did for this story in BusinessWeek–that it will take something much more potent than resveratrol to produce an anti-aging effect.

Drug giant GlaxoSmithKline purchased Sirtris for an eye-popping $720 million in 2008. Together the companies are studying compounds that stimulate sirtuins. But as the Technology Review story points out, last month Glaxo stopped recruiting patients for a trial of one of Sirtris’ resveratrol compounds, which is being studied to treat multiple myeloma. The company said it needs time to figure out why some patients are developing a dangerous kidney ailment. And Pfizer published a study earlier this year questioning whether one of Sirtris’ other compounds even targets sirtuins effectively.

If the sirtuin approach or others someday prove to be effective, the companies developing these drugs will still have a basic problem: The FDA doesn’t recognize aging as a disease. So instead the companies will have to test their drugs in diseases that are common in aging people, such as cancer and diabetes. And judging from recent news, even that is likely to be a challenge.

What’s the moral of the story? Don’t count on a pill–or a hormone injection, supplement or any other tonic–to extend your life. Age happens. There’s no shortcut to preventing it.

 
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Posted in Resveratrol, Science of Aging

 
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