A Clue to Living Longer
Growth hormone and insulin may explain why restricting calories boosts longevity

SOURCE: “Targeted Disruption of Growth Hormone Receptor Interferes with the Beneficial Actions of Calorie Restriction” M. S. Bonkowski et al.Proceedings of the National Academy of Sciences 103(20): 7901-7905

RESULTS: Scientists at the Southern Illinois School of Medicine discovered that mice engineered to be resistant to growth hormone have a longer life span than normal mice; the increase is similar to that seen in normal mice fed a diet low in calories, but engineered mice fed a low-calorie diet showed no additional gain in longevity. Both the engineered mice and the calorie-restricted normal mice were much more sensitive to insulin, suggesting a possible mechanism for the increase in longevity.

WHY IT MATTERS: Scientists have long known that a low-calorie but nutritionally adequate diet can boost longevity in organisms as diverse as yeast, flies, and mice. But they don’t know why. (See “Is Defeating Aging a Dream?”) That the hormone-resistant mice mimic the longevity of calorie-restricted mice is an important clue to the mechanisms responsible for those effects. Scientists hope to one day design drugs that target the underlying biological pathway and thereby increase life span or treat age-related disease without dietary restrictions.

METHODS: The scientists used genetically engineered mice that lacked the receptor for growth hormone. Engineered and normal mice were then fed a normal or a calorie-restricted diet.

NEXT STEPS: The researchers plan to investigate which of the many effects of caloric restriction lead to increased longevity. They will also test the hypothesis that insulin sensitivity is an important determinant of life span.

Microbial Drug Factories
Synthetically engineered micro-örganisms could provide a cheap way to manufacture drugs

SOURCE: “Production of the Antimalarial Drug Precursor Artemisinic Acid in Engineered Yeast” D. K. Ro et al.Nature 440(7086): 940-943

RESULTS: Dae-Kyun Ro, Jay Keasling (who wrote a “Notebook” entry), and colleagues at the University of California, Berkeley, have genetically engineered yeast to produce large quantities of artemisinic acid, a precursor to the malaria drug artemisinin.

WHY IT MATTERS: Artemisinin combination therapies are an effective treatment for malaria. But the drugs, which are derived from the sweet wormwood tree, are expensive and in short supply. More-efficient manufacturing methods could reduce the cost of the malaria drugs to the point that a larger number of people in poor countries could afford them. The work also illustrates the great potential of synthetic biology – the attempt to design and create organisms to perform specific functions.

METHODS: The researchers re-designed the metabolic pathways of yeast to more efficiently make an artemisinin precursor called amorphadiene, which plants naturally make in small quantities. Using a newly identified wormwood gene, they further engineered the yeast to complete the last few steps of the synthesis process to create artemisinic acid.

NEXT STEPS: Keasling’s team will continue to fine-tune the system to make it even more efficient and therefore more cost effective. It will also scale up the manufacturing process in collaboration with Amyris Biotechnologies, a company in Emeryville, CA, that was founded to commercialize the technology.

From the Labs: Nanotechnology
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