Biochemical twist in yeast holds key to longevity

March 25th, 2009 - 3:14 pm ICT by ANI  

Washington, Mar 25 (ANI): Johns Hopkins researchers have discovered a new energy-making biochemical twist that can boost the lifespan of yeast cells, and can even do the same for humans.
The findings have revealed that making glucose is highly influenced by a large enzyme complex already known to fix damaged DNA, and which apparently affects yeast life span through a common chemical process-acetylation.
In their study, the researchers showed that constant acetylation of the so-called NuA4 enzyme complex causes yeast cells to live longer than they would under normal conditions.
The team genetically modified yeast cells, designing one to mimic the constantly acetylated form of the enzyme and another to mimic the constantly de-acetylated form.
Then they compared these two mutants to a cell in which nothing was genetically altered.
It was found that the constantly acetylated form of yeast cell lives 20 percent more than the unaltered cell and that the constantly de-acetylated form had an 80 percent reduction in its lifespan compared to the unaltered cell.
“Because the NuA4 complex is highly conserved among species, what we”ve found in yeast translates to humans as well,” explained Heng Zhu, Ph.D., an assistant professor of pharmacology and molecular sciences at the Johns Hopkins University School of Medicine.
He added: “What we”ve revealed about longevity in yeast perhaps someday can translate to human health.”
The researchers used a yeast proteome chip - a glass slide containing 5,800 or more than 80 percent coverage of all of the yeast-encoded proteins - and hunted along the string of proteins to find specific molecular targets of the NuA4 complex.
After analysing yeast proteome chip and noting which proteins had an acetyl group stuck to them after adding NuA4, the researchers identified more than 90 such possible targets.
In order to know which of these would naturally be acetylated, researchers closed in on a random set of 20 to test further, and ultimately confirmed13 as targets of the NuA4 complex.
More than simply expanding the list of known targets from three to 13, the team provided the first evidence that acetylation controls the activity of an enzyme called Pck1p, critical to sugar production in yeast and probably human cells.
The enzyme Sir2, which removes the acetyl group, also controls the enzyme.
Sir2 is heavily implicated in aging and a number of diseases by recent studies in mammals.
“The new function we identified for Pcklp is regulation of glucose-making, which is what all cells do to survive under conditions of starvation,” explained Zhu.
The study is published in the latest issue of Cell. (ANI)

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