Researchers uncover details about how dietary restriction slows ...( University of Washington scientists ...)

University of Washington scientists have uncovered details about the mechanisms through which dietary restriction slows the aging process. Working in yeast cells, the researchers have linked ribosomes, the protein-making factories in living cells, and Gcn4, a specialized protein that aids in the expression of genetic information, to the pathways related to dietary response and aging. The study, which was led by UW faculty members Brian Kennedy and Matt Kaeberlein, appears in the April 18 issue of the journal Cell.

Previous research has shown that the lifespan-extending properties of dietary restriction are mediated in part by reduced signaling through TOR, an enzyme involved in many vital operations in a cell. When an organism has less TOR signaling in response to dietary restriction, one side effect is that the organism also decreases the rate at which it makes new proteins, a process called translation.

In this project, the UW researchers studied many different strains of yeast cells that had lower protein production. They found that mutations to the ribosome, the cell's protein factory, sometimes led to increased life span. Ribosomes are made up of two parts -- the large and small subunits -- and the researchers tried to isolate the life-span-related mutation to one of those parts.

What we noticed right away was that the long-lived strains always had mutations in the large ribosomal subunit and never in the small subunit, said the study's lead author, Kristan Steffen, a graduate student in the UW Department of Biochemistry.

The researchers also tested a drug called diazaborine, which specifically interferes with synthesis of the ribosomes' large subunits, but not small subunits, and found that treating cells with the drug made them live about 50 percent longer than untreated cells. Using a series of genetic tests, the scientists then showed that depletion of the ribosomes' large subunits was likely to be increasing lif
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