Key protein may explain the anti-aging and anti-cancer benefits of dietary restriction

Discovery gives scientists new targets for developing and testing drugs that could extend the healthy years of life

A protein that plays a key role in tumor formation, oxygen metabolism and inflammation is involved in a pathway that extends lifespan by dietary restriction. The finding, which appears in the May 22, 2009 edition of the on-line journal PLoS Genetics, provides a new understanding of how dietary restriction contributes to longevity and cancer prevention and gives scientists new targets for developing and testing drugs that could extend the healthy years of life.

The protein is HIF-1 (hypoxia-inducible factor 1). It helps cells survive by "turning on" when oxygen levels are low. HIF-1 is also active in some forms of human cancer. HIF-1 overexpression is frequently detected in solid tumors; inhibition of HIF-1 has been proved to be an efficient way to prevent cancer growth. Now, scientists at the Buck Institute for Age Research have shown that HIF-1 is also a key player in dietary restriction. HIF-1 is involved in a molecular pathway known to regulate cell growth and metabolism in response to nutrients and growth factors.

"Previous studies on HIF-1 have mainly focused on its roles in oxygen metabolism and tumor development", said Buck faculty member Pankaj Kapahi, PhD, lead author of the study.

Kapahi says the study encourages the investigation of HIF-1 in nutrient sensing pathways. "The data in this study also points to HIF-1 as a likely target for regulating the protective effects of dietary restriction in mammals," said Kapahi.

"Dietary restriction is one of the most robust methods for extending lifespan and delaying age-related disease among various species."

Kapahi says the molecular mechanisms involved in how dietary restriction slows cancer and extends lifespan have been largely unknown. "This study gets us closer to understanding that process and gives us better targets for both designing and testing drugs which could mimic the effects of dietary restriction in humans," said Kapahi.