Key protein may explain how dietary restriction contributes to longevity, cancer prevention

Washington, May 22 (ANI): An Indian-origin researcher says that studying a protein that plays a key role in tumour formation, oxygen metabolism, and inflammation may help understand the anti-aging and anti-cancer benefits of dietary restriction, say researchers.

Dr. Pankaj Kapahi, of the Buck Institute for Age Research, has revealed that the protein is called hypoxia-inducible factor 1 (HIF-1), which helps cells survive by "turning on" when oxygen levels are low, and is also active in some forms of human cancer.

He further highlights the fact that HIF-1 overexpression is frequently detected in solid tumours, and that its inhibition has been proved to be an efficient way to prevent cancer growth.

He says that the current study has shown that HIF-1 is also a key player in dietary restriction.

The researcher says that 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," he said.

Dr. Kapahi says that his 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. Dietary restriction is one of the most robust methods for extending lifespan and delaying age-related disease among various species," he said.

According to the researcher, 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," he said.

For their study, the researchers genetically altered nematode worms to both under and over-express HIF-1.

The animals, which are the most-often used model to study aging, were fed different diets.

The researchers said that the animals that were designed to over-express HIF-1 did not get the benefit of lifespan extension, even though their diets were restricted.

They further revealed that the animals that under-expressed HIF-1 lived longer, even when they had a nutrient-rich diet.

The research team also observed the lifespan extension resulting from dietary restriction required activity in signalling pathways in the endoplasmic reticulum, the part of the cell involved in processing and the proper folding of proteins.

This finding supports the theory that aging stems from the effects of misfolded proteins, and opens up a rich area of investigation to examine the mechanisms by which stress in the endoplasmic reticulum affects lifespan.

The study has been published in the on-line journal PLoS Genetics. (ANI)