10-Fold Life Span Extension Reported In Baker's Yeast
"We're setting the foundation for reprogramming healthy life," says study leader Valter Longo of the University of Southern California.
Longo's group put baker's yeast on a calorie-restricted diet and knocked out two genes - RAS2 and SCH9 - that promote aging in yeast and cancer in humans.
"We got a 10-fold life span extension that is, I think, the longest one that has ever been achieved in any organism," Longo says. Normal yeast organisms live about a week.
"I would say 10-fold is pretty significant," says Anna McCormick, chief of the genetics and cell biology branch at the National Institute on Aging (NIA) and Longo's program officer. The NIA funds such research in the hope of extending healthy life span in humans through the development of drugs that mimic the life-prolonging techniques used by Longo and others, McCormick adds.
Baker's yeast is one of the most studied and best understood organisms at the molecular and genetic level. Remarkably, in light of its simplicity, yeast has led to the discovery of some of the most important genes and pathways regulating aging and disease in mice and other mammals.
Longo's group next plans to further investigate life span extension in mice. The group is already studying a human population in Ecuador with mutations analogous to those described in yeast.
"People with two copies of the mutations have very small stature and other defects," Longo says. "We are now identifying the relatives with only one copy of the mutation, who are apparently normal. We hope that they will show a reduced incidence of diseases and an extended life span."
Longo cautions that, as in the Ecuador case, longevity mutations tend to come with severe growth deficits and other health problems. Finding drugs to extend the human life span without side effects will not be easy.
In the PLoS Genetics study, Longo's group identifies a major overlap between the genes previously implicated in life span regulation for yeast and mammals and those involved in life span extension under calorie restriction.
"We identified three transcription factors … that are very important for the effect of calorie restriction, but at the same time, we also showed that it's not enough because even without these transcription factors, calorie restriction can still extend life span a little bit," Longo says.
"So that means that we've identified a lot of the key players in the calorie restriction effect but not all of them."
Calorie restriction - in practice, controlled starvation - has long been shown to reduce disease and extend life span in species from yeast to mice.
Scientists believe that a nutrient shortage kicks organisms into a maintenance mode, enabling them to re-direct energy from growth and reproduction into anti-aging systems until the time they can feed and breed again. Calorie restriction is now being tested by other researchers on primates and even humans, Longo says.
Wei M, Fabrizio P, Hu J, Ge H, Cheng C, et al. (2008) "Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9." PLoS Genet 4(1): e13. doi:10.1371/journal.pgen.0040013
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