A Genetic Fountain of Youth

By disabling a gene involved in an important biochemical signaling pathway, scientists have discovered a way to mimic the well-known anti-aging benefits of caloric restriction, allowing mice to live longer and healthier lives. This finding, published online today in Science, offers a promising drug target for combating the many health problems associated with aging.

"This research points the way to potential pharmacological approaches to treating aging-related diseases in humans," says senior author Dominic Withers, professor of diabetes and endocrinology at University College London.

"It really defines this as a pathway that's affecting aging all the way from yeast to mammals, which I think is pretty striking," says Matt Kaeberlein, professor of pathology at the University of Washington and coauthor of a commentary accompanying the new study.

Caloric restriction has long been known to extend lifespan and reduce the incidence of age-related diseases in a wide variety of organisms, from yeast and roundworms to rodents and primates. Exactly how a nutritionally complete but radically restricted diet achieves these benefits has remained unclear. But recently several studies have offered evidence that a particular signaling pathway, involving a protein called target of rapamycin (TOR), may play a pivotal role. This pathway acts as a sort of food sensor, helping to regulate the body's metabolic response to nutrient availability.

Withers and colleagues noticed that young mice with a disabled version of the protein S6 kinase 1 (S6K1), which is directly activated by TOR, bore strong resemblance to calorie-restricted mice: they were leaner and had greater insulin sensitivity than normal mice. The researchers wondered whether these benefits would persist into middle and late age, and whether the mice would live longer.

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A Startup That Builds Biological Parts

In a warehouse building in Boston, wedged between a cruise-ship drydock and Au Bon Pain's corporate headquarters, sits Ginkgo BioWorks, a new synthetic-biology startup that aims to make biological engineering easier than baking bread. Founded by five MIT scientists, the company offers to assemble biological parts--such as strings of specific genes--for industry and academic scientists.

"Think of it as rapid prototyping in biology--we make the part, test it, and then expand on it," says Reshma Shetty, one of the company's cofounders. "You can spend more time thinking about the design, rather than doing the grunt work of making DNA." A very simple project, such as assembling two pieces of DNA, might cost $100, with prices increasing from there.

Synthetic biology is the quest to systematically design and build novel organisms that perform useful functions, such as producing chemicals, using genetic-engineering tools. The field is often considered the next step beyond metabolic engineering because it aims to completely overhaul existing systems to create new functionality rather than improve an existing process with a number of genetic tweaks.

Scientists have so far created microbes that can produce drugs and biofuels, and interest among industrial chemical makers is growing. While companies already exist to synthesize pieces of DNA, Ginkgo assembles synthesized pieces of DNA to create functional genetic pathways. (Assembling specific genes into long pieces of DNA is much cheaper than synthesizing that long piece from scratch.)

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