30 June 2009

Diet and longevity: the molecular relationship

The phenomenon of increasing life expectancy, subject to diet, has been studied for 70 years. Similar results were obtained for various species: from yeast to fish and mammals, including primates. But until recently, very little was known about the genetic mechanisms underlying longevity. The situation changed when, about two years ago, Andrew Dillin and colleagues from the Salk Institute for Biological Research (USA) showed that the transcription factor PHA-4 takes part in these processes in Caenorhabditis elegans worms (humans have three similar genes belonging to the FOXA family). According to the data obtained, the principle of increasing the life span of an organism with reduced calorie intake is based on the interaction of genetic factors and environmental factors: reducing the amount of nutrients includes genetic processes that determine life expectancy. A new study, also performed in the Dillin laboratory (Andrea C. Carrano et al., A conserved ubiquitination pathway determines longevity in response to diet restriction), showed the role of other elements of this metabolic pathway in the regulation of life expectancy.

It is known that knockout of the WWP-1 gene involved in the process of protein degradation in C.elegans leads to increased sensitivity of animals to external stressors. These data allowed Dillin and colleagues to suggest that this gene and its protein product play a role in the regulation of life expectancy. They showed that worms mutated by WWP-1 protein, while following a low-calorie diet, live longer than worms with a normally functioning protein contained on the same feed. Preliminary studies indicate that this effect is achieved with the participation of another enzyme – UBC-18, working in tandem with WWP-1. It has also been shown that C.elegans with an increased level of WWP-1 expression live 25% longer than normal worms, even without dieting.

Since the described metabolic pathway is conservative, it is hoped that the data obtained on C.elegans will be relevant for humans as well. The authors of the study hope to discover compounds that would be able to influence the activity of enzymes and mimic the observance of a low-calorie diet, contributing to the prolongation of life without changing the diet.

Currently, work is underway in Dillin's laboratory to search for WWP-1 and UBC-18 receptors, which should be the main regulators of the entire process. A search is also underway for small molecules that can affect the activity of both enzymes.

Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: Proteins link diet to longevity30.06.2009

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