Gerontology Comes of Age

In 1923, at age 67, Sigmund Freud had a vasectomy. By signing up for the Steinach operation--as the procedure, named for the Austrian endocrinologist Eugen Steinach, was then known--the famed psychiatrist was less concerned with sex than he was with longevity. Nearly a century ago it was believed that tying off one's spermatic cords could thwart the effects of aging.

In the succeeding decades, scientists moved from one idea to another in search of a procedure or pill that could improve longevity. As we learn in David Stipp's "The Youth Pill," research may be finally catching up with aspiration. "The rate of aging in widely diverse organisms [turns] out to be not only amazingly plastic but also controlled in a way that has enabled scientists to slow it down with readily available interventions," writes Mr. Stipp, a former reporter for Fortune magazine and The Wall Street Journal.

Mr. Stipp offers an engaging account of the burgeoning field dubbed gerontology--the study of aging and of medicinal tools to block its unwanted effects. The most compelling theory has settled on a series of genes that are activated when people are fed a low-calorie diet. This science of calorie restriction, or "CR," as it is called in medical literature, stems from studies of an eccentric group of people who engage in near-starvation diets as a way to extend their lives. Mr. Stipp believes that this line of research holds the best promise of a pharmaceutical product that could slow the degenerative effects of aging

The scare over the sirtuin treatment is just the sort of unhappy event that explains why drug developers are increasingly unwilling to take on the technical and regulatory risks of exploring new science.

There is general agreement in gerontology circles that the biological effects of CR can confer benefits, such as modulating our endocrine systems to lower our levels of blood sugar. But that's where the consensus unravels. Scientists spar over the precise genes (dubbed gerontogenes) that govern anti-aging effects and over what drug compounds are best suited to target them.

One scientific camp pursues a gene called TOR (for target of rapamycin, a compound that can control the production of cell protein, among other attributes). The National Institute of Aging--a branch of the National Institutes of Health with a $1 billion annual budget--has been quietly testing possible anti-aging agents since 2003, with TOR among the most promising. Rapamycin in drug form is used to prevent rejection in organ transplants. The drug has some nasty side effects, but in small doses seems to activate TOR's benefits: Rapamycin extended the lifespan of mice by 14% in one recent study.

Another scientific faction has settled on a gene called SIRT1, which instructs the body to make a set of enzymes that have been shown to extend the lives of worms, flies and mice. One compound that activates SIRT1 is resveratrol; oenophiles were delighted several years ago to learn that resveratrol can be found in red wine.

The Food and Drug Administration doesn't recognize aging as a disease, so gerontology research focuses for now on targeting diseases associated with old age, like diabetes and Parkinson's. "A true anti-aging drug should, almost by definition, avert or slow the progression of a wide array of degenerative diseases that arise late in life," Mr. Stipp writes. "Value could be unlocked by developing it as a conventional prescription drug that could address a whole slew of major diseases."

Mr. Stipp traces a dozen biotech firms chasing gerontogenes, but none has been more celebrated, or more controversial, than Sirtris, a company in Cambridge, Mass., founded by one of the biotech industry's most successful venture capitalists, Christoph Westphal.

Sirtris was formed on the premise that resveratrol could activate SIRT1, and the company's researchers set out to discover similar compounds (called sirtuin mimetics) that would be more potent activators of this possibly life-extending gene. Scientific peers have recently called into question some of the early experiments that Sirtris used to bolster its claims for resveratrol and similar compounds. Competing researchers say these beneficial effects were the product of a chance finding, or even lab error. Sirtris maintains that its anti-aging results are real. The debates, and scientific work, continue.

Sirtris is also closely watched for what it achieved in the capital markets. The biotech raised more than $100 million in venture funding before its $63 million initial public offering in 2007; the feat showed that gerontology had arrived as a science that merited investment. In 2008, pharmaceutical giant GlaxoSmithKline acquired Sirtris for $720 million. A field that was once shunned as quackery is now inviting billions of dollars in pharmaceutical investment and is, as Mr. Stipp says, going mainstream.

In May, one of the first of the resveratrol-related sirtuin drugs, named SRT501, ran into trouble. A small trial in multiple myeloma, a cancer of certain cells of bone marrow, was put on hold when some patients developed kidney problems, although it's not clear that the drug was the culprit.

The scare over the sirtuin treatment is just the sort of unhappy event that explains why drug developers are increasingly unwilling to take on the technical and regulatory risks of exploring new science. Start-up drug firms--and their investors--are more inclined than ever to make safe bets on "specialty" pharmaceuticals, which are essentially repurposed medicines. But as "The Youth Pill" makes clear, an adventurous few researchers and companies remain undeterred. They are willing to confront the unpredictable, expensive and sluggish process of drug development to work on SIRT genes, TOR and other promising areas of gerontology as the search for the fountain, or at least the gel cap, of youth continues.

Scott Gottlieb, M.D., is a resident fellow at AEI.

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