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Caffeine Adds Life (to Yeast)

Scientists are getting a better idea of how coffee might extend human life spans. Hint: It might follow the same path to immortality as eating less.
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Professor and scientist Claudio De Virgilio drinks lots of strong coffee. His latest research suggests he is extending his lifespan by a unique mechanism.

De Virgilio and his collaborators from the University of Fribourg and the University of Geneva in Switzerland investigated the role caffeine plays in promoting longer life in baker’s yeast. The report suggests that caffeine uses the same biochemical pathway that taking in at least 25 percent fewer calories follows in extending life span.

Limiting caloric intake while maintaining adequate nutrition lengthens life span in all the species investigated so far, including yeast, worms and dogs. It also reduces age-related diseases, including cardiac and neurodegenerative diseases.

Reasons for these benefits have been linked to such broad processes as nutritional sensing and inflammatory regulation. But the precise biochemical pathways — how one protein triggers the activity of the next — are just starting to become clearer as a result of detailed genetic and biochemical investigations. Understanding these mechanisms will provide targets for compounds aimed at slowing or preventing age-related disease.

Yeast, a single-celled organism, provides a model system for investigating nutrient signaling — a process surprisingly similar to the mammalian counterpart. De Virgilio and Robbie Loewith, investigators of the study, have devoted their career to the study of growth and nutritional sensing in yeast. With De Virgilio’s data regarding specific proteins involved in detecting and responding to nutrition and Loewith’s interest in discovering substances that inhibit the TOR complex, the project came together.

Growing yeast in caffeinated media, the scientists used biochemistry and genetics to determine which yeast proteins are influenced by caffeine. Results published in the July 2008 issue of Molecular Microbiology show caffeine uses a new mode of action to increase life span in yeast. Caffeine inhibited the activity of specific proteins involved with such vital functions as growth, stress and metabolism. The key proteins investigated, associated with the TOR pathway, are major players in
the dietary restriction life-extending process.

Caffeine is the most widely used psychoactive drug in the world. Its most recognized mode of action is via the binding of brain receptors involved with stimulation. However, studies within the last few years — the first by Loewith himself — have widened the biochemical role of caffeine in cells to include TOR interaction.

De Virgilio believes that the pathways for caloric restriction and caffeine follow the same mechanism but also may complement each other. “It’s possible that calorie restriction and caffeine treatment, within a limited range, act additively to extend yeast life span,” he said.

Given that the proteins involved have human counterparts and that recent studies show coffee consumers are more likely to live longer, the scientists speculate caffeine acts similarly in people as in yeast. However, De Virgilio added, “Even though we like yeast as an ‘ultimate model system,’ we have to take notice that humans are a bit more complicated than yeast cells. It is likely, therefore, that humans express additional proteins that may be targeted by caffeine.”

Scaling up the caffeine quantities and protein activity effect from yeast to human levels, the research team concluded that moderate coffee intake would be sufficient to extend life.

Of course, coffee contains compounds in addition to caffeine. Some, like antioxidants, are associated with beneficial effects, while others, like cafestol, are associated with such negative consequences as cholesterol increase. Still, coffee is not thought to be harmful, and even cafestol can be retained by a paper filter.

De Virgilio speculated, “Drinking filtered coffee at a moderate level is maybe a good way to go if one wishes to live forever or, at least, longer.”

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