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Research Article

Life Span Extension by Calorie Restriction Depends on Rim15 and Transcription Factors Downstream of Ras/PKA, Tor, and Sch9

  • Min Wei equal contributor,

    equal contributor Contributed equally to this work with: Min Wei, Paola Fabrizio

    Affiliations: Andrus Gerontology Center, University of Southern California, Los Angeles, California, United States of America, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America

    X
  • Paola Fabrizio equal contributor,

    equal contributor Contributed equally to this work with: Min Wei, Paola Fabrizio

    Affiliations: Andrus Gerontology Center, University of Southern California, Los Angeles, California, United States of America, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America

    X
  • Jia Hu,

    Affiliation: Andrus Gerontology Center, University of Southern California, Los Angeles, California, United States of America

    X
  • Huanying Ge,

    Affiliation: Department of Computational and Molecular Biology, University of Southern California, Los Angeles, California, United States of America

    X
  • Chao Cheng,

    Affiliation: Department of Computational and Molecular Biology, University of Southern California, Los Angeles, California, United States of America

    X
  • Lei Li,

    Affiliation: Department of Computational and Molecular Biology, University of Southern California, Los Angeles, California, United States of America

    X
  • Valter D Longo mail

    To whom correspondence should be addressed. E-mail: vlongo@usc.edu

    Affiliations: Andrus Gerontology Center, University of Southern California, Los Angeles, California, United States of America, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America

    X
  • Published: January 25, 2008
  • DOI: 10.1371/journal.pgen.0040013

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Copy of the Press Release Originally Distributed, January 16th, 2008

Posted by PLoS_Genetics on 03 Feb 2009 at 17:14 GMT

10-Fold Life Span Extension Reported in Baker’s Yeast

Researchers have created baker’s yeast capable of living to 800 in yeast years without apparent side effects. The basic but important discovery, achieved through a combination of dietary and genetic changes, brings scientists closer to controlling the survival and health of the unit of all living systems: the cell. A full report of the study will be published in the open-access journal PLoS Genetics on January 25, 2008. A preliminary version of the work is available online.

“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.


Press Coverage

PLoS_Genetics replied to PLoS_Genetics on 03 Feb 2009 at 17:15 GMT