General Health
Study explains why dietary restriction extends lifespan
By Sue Mueller
Apr 17, 2008 - 11:16:04 PM

TURSDAY April 17, 2008 (foodconsumer.org) -- Dietary restriction is known to extend lifespan, at least in some animals.  University of Washington researchers have now uncovered the mechanisms through which dietary restriction slows the aging process.

The researchers conducted the study in yeast cells and found that ribosomes, the protein making factories in living cells and Gcn4, a protein involved in the expression of genetic information are associated with dietary response and aging.

Previous studies have showed the lifespan-extending properties of dietary restriction are mediated partially by reduced signaling through an enzyme known as TOR.  In response to dietary restriction, TOR signaling was reduced and thus translation, a process involved in the making of proteins was also slowed.

In the current study, Brian Kennedy and Matt Kaeberlein investigated many types of yeast cells that had lower protein production and found strains with mutations in the ribosome were sometimes associated with longer lifespan.

They also found the lifespan extending mutations always were found in the large ribosomal subunit, said Kristan Steffen, a graduate student in the UW Department of Biochemistry.  Ribosomes are made up of two subunits, one large and another small.

Using a drug known as diazaborine, which interferes with synthesis of the ribosomes' large subunits, but not the small ones, the researchers found cells treated with the drug lived about 50 percent longer than untreated cells.

Genetic tests also revealed depletion of the ribosomes' large subunits was likely to increase lifespan by a mechanism related to dietary restriction.

The researchers also found when ribosomes are not working at 100 percent capacity, production of most proteins are slowed but production of Gcn4 is enhanced in the long-lived yeast cells.

Cells lacking Gcn4 could not have their lifespan extended, the study showed.

Worms, flies, mice and humans who have been observed to respond to dietary restriction all have Gcn4-like proteins that appear to be regulated in a similar way, according to Kennedy.

The study was published in the April 18 issue of the journal Cell.