25 May 2009

Prolonging life and a low-calorie diet: another connecting link

HIF-1 protein (hypoxia-inducible factor 1, hypoxia-induced factor 1) promotes cell survival at low oxygen levels. Some types of solid tumors are characterized by a high level of HIF-1 activity, and suppression of its expression contributes to stopping their growth. Now scientists from the American Institute for Age Research named after Leonard and Beryl Bakov (Buck Institute for Age Research) demonstrated that HIF-1 is also activated under conditions of limited nutrient intake, taking part in the regulation of cell growth and metabolic processes.

According to Dr. Pankaj Kapahi, who heads the study, HIF-1 was previously studied mainly in terms of its role in oxygen metabolism and tumor growth. The present study draws attention to the role of this protein in the work of nutrient-dependent signaling pathways and the aging process. The particular importance of the discovery, according to the authors, is the possibility of studying previously unclear mechanisms of the effect of a low-calorie diet on cancer development and life expectancy, and to develop new drugs based on the data obtained.

The study was performed on C.elegans nematodes, the most commonly used to study the molecular basis of aging. Transgenic nematodes – with reduced and increased levels of HIF-1 expression – were kept on different diets. Animals with a high level of HIF-1 expression were characterized by a short life span, even if they received a feed with a low nutrient content, whereas nematodes with a low level of HIF-1 expression, on the contrary, turned out to be long-lived regardless of the diet. In addition, it was found that an increase in life expectancy with a low–calorie diet is associated with an increase in the activity level of the signaling pathways of the endoplasmic reticulum - the part of the cell where proteins are "stacked" into their characteristic three-dimensional structures. This discovery supports the theory that one of the foundations of aging is precisely a violation of the mechanism of protein folding, and opens up a vast field for the study of this theory.

Article by Di Chen et al. HIF-1 Modulates Dietary Restriction-Mediated Lifespan Extension via IRE-1 in Caenorhabditis elegans published in PLoS Genetics.

Portal "Eternal youth" http://vechnayamolodost.ru based on Newswise: Identification of Key Protein May Explain Anti-cancer, Anti-aging Benefits of Dietary Restriction25.05.2009

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