The molecular mechanisms involved in how dietary restriction slows cancer and extends lifespan have been largely unknown - until now. A new study conducted by scientists at the Buck Institute for Age Research sheds light on how the protein HIF-1 (hypoxia-inducible factor 1), which is involved in tumor formation, oxygen metabolism and inflammation, is also involved in a pathway that extends lifespan by dietary restriction. According to the scientists, the HIF-1 protein helps enable cells to survive by "turning on" when oxygen levels are low. The protein is also active in some forms of cancer, and in fact, inhibition of HIF-1 has been shown to be an efficient way to prevent the growth of cancerous tumors. The scientists have now been able to show that HIF-1 is also involved in a molecular pathway that is known to regulate cell growth and metabolism in response to nutrients and growth factors. The finding, which was published in the online journal PloS Genetics, may provide new targets for developing and testing drugs that could extend life.

The study involved nematode worms, which are the most-often used model to study aging. The worms were genetically altered to both under- and over-express HIF-1. The researchers found that those worms designed to over-express HIF-1 did not get the benefit of lifespan extension, although their diets were restricted. Animals that under-expressed HIF-1 lived longer, even when they had a nutrient-rich diet.

As lead author and Buck faculty member, Pankaj Kapahi, Ph.D. notes, this study helps scientists better understand the molecular mechanisms involved in how dietary restriction slows cancer and extends lifespan. And he says, "It gives us better targets for both designing and testing drugs which could mimic the effects of dietary restriction in humans. Previous studies on HIF-1 have mainly focused on its roles in oxygen metabolism and tumor development. The data in this study also points to HIF-1 as a likely target for regulating the protective effects of dietary restriction in mammals." And he adds, "Dietary restriction is one of the most robust methods for extending lifespan and delaying age-related disease among various species."

News Release: Key protein may explain the anti-aging and anti-cancer benefits of dietary restriction  www.firstscience.com  May 15, 2009