Live long and alter

Changes in yeast cells help explain caloric restriction’s longevity boost

Normal 0 false false false MicrosoftInternetExplorer4 GOTHENBURG, Sweden — Less food doesn’t always mean less energy. Restricting the diet of yeast cells makes them live about 30 percent longer than normal, scientists have known. But new research shows that these calorie-restricted cells make just as much ATP — the energy currency of cells — as do yeast cells fed a normal diet.

The cells have just as much energy available, so they are not really starving, says research leader Vladimir Titorenko, a molecular biologist at ConcordiaUniversity in Montreal, Canada.

“It’s not a starvation; it’s just a specific sort of remodeling of the cells’ metabolism in a way that also causes the organism to live longer,” Titorenko says.

Titorenko and his team fed yeast cells a limited diet that contained 30 to 50 percent fewer calories than normal but was still nutritionally complete. In response, the cells cut back on making lipids and instead rerouted energy to making ATP, according to the unpublished research, which was presented August 25 at the International Conference on Systems Biology.

Normally, lipid molecules such as free fatty acids accumulate in yeast cells. This impairs the cells and can even cause them to self-destruct. So diverting energy away from making these lipids could help explain why calorie restriction prolongs the cells’ lifespan, Titorenko says.

“It is interesting that yeast on calorie restriction produce just as much ATP as well-fed ones,” comments David Sinclair, an expert on calorie restriction and aging at HarvardMedicalSchool in Boston.

By taking a sweeping look at the effects of calorie restriction on the cells’ genetic activity, protein interactions and other internal workings, Titorenko’s team identified other changes that appear to promote longer life for the cells.

Scientists have known since the 1930s that mice and other animals fed a restricted diet live substantially longer. These animals are also less prone to chronic diseases associated with aging such as diabetes, Alzheimer’s-like diseases and cancer. Only in the past 10 years or so have scientists begun to understand the molecular causes of this longevity boost, and many of the cellular effects of calorie restriction remain unknown.

In addition to changes in lipid production, Titorenko’s team found that some of the changes in the cells stimulate mitochondria, the “power plants” of cells. As a consequence, these mitochondria churn out free radicals such as hydrogen peroxide at doses too low to do much damage to the cells but high enough to activate the cells’ stress-response proteins. These groups of proteins go around fixing damage in the cells, a kind of house cleaning that can also help the cells live longer.

“There is renewed interest in mitochondria as researchers discover their key role in mediating the effects of caloric restriction and resistance to diseases of aging such as diabetes and neurodegeneration,” Sinclair says.

Another typical sign of aging is the accumulation of clumps of misfolded proteins. In people, such clumps are a hallmark of degenerative diseases such as Alzheimer’s. Calorie restriction boosted the yeast cells’ production of a sugar called trehalose, Titorenko reports. This sugar binds to misfolded proteins and prevents them from clumping together.

“It protects the cells because it protects proteins from aggregating,” Titorenko says. If the effect of calorie restriction on production of this sugar is the same in mammals, he says, it could help explain how such a diet stalls the onset of these degenerative diseases in lab animals.

Scientists know that yeast share some aging mechanisms with people, but more research is needed to show whether all the effects of calorie restriction seen in yeast cells also occur in animals and humans, Titorenko says.

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