Yeast Life Extended Ten Times; Offers Hope for Humans

Amitabh Avasthi
for National Geographic News
January 28, 2008
Scientists have discovered a means to extend the life span of yeast cells tenfold—and they say further research on unusual communities in Ecuador might offer hope for humans too.

The researchers achieved the feat by deleting two genes—SCH9 and RAS2—from baker's yeast and then subjecting the yeast cells to extreme starvation by restricting their calorie intake.

"Both these genes control cellular function and normally promote cell division and cell growth," said study leader Valter Longo, a biogerontologist at the University of Southern California in Los Angeles. "They are very similar to two of the main cancer-causing genes in humans."

But removing the genes alone does not do the trick. Increased life span in yeast appears to be linked to calorie restriction as well.

Such restriction reduces the activation of those genes, in turn activating an enzyme called Rim 15, Longo said.

(Related: "Long Life Span in Flies Reversed By Just Whiff of Food" [February 1, 2007].)

"[Rim15] triggers a number of proteins that comprise stress-protective systems in yeast cells," he added.

These proteins control antioxidant and DNA-repair enzymes and regulate the proper folding of proteins, which may explain the dramatic increase in yeast longevity.

But exactly how many of these proteins go about their jobs is still unclear.

"There are probably hundreds of genes which play different roles that are part of this switch from 'growth' mode to 'protective' mode. We're looking for them right now," said Longo, whose findings appeared in recent issues of PLoS Genetics and the Journal of Cell Biology.

Human Connection

Other researchers had previously identified genetic mutations in mice that reduced the amount of growth hormone produced. This increased the animals' life span by 50 percent and conferred protection against several diseases.

Now Longo's group is studying a human population in Ecuador with a similar mutation that controls the production of human growth hormone.

(Read "Secrets of Longevity" in National Geographic magazine.)

The gene also influences the human analogs of SCH9 and RAS2, which are located further down the growth hormone pathway.

"When you have low growth hormone, you tend to store fat," Longo said, which in turn affects the overall aging process.

That's because during times of food shortages, "all the energy has to be stored to make sure that aging is as slow as possible so that you can make it the next round of food."

So far the researchers have collected DNA from 300 people. Their next goal is to understand the rates of mortality and cancer in the population, as well as why these people do not appear to suffer from diabetes.

"People with two copies of the mutations have very small stature and other defects," Longo said in a press statement. "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."

"Far Out"

Dan Buettner is a longevity expert and a National Geographic Society Expeditions Council grantee who was not involved in the current study. (National Geographic News is a division of the National Geographic Society.)

His grant has taken him all over the world to places he calls Blue Zones where people live the longest.

He is not convinced that the combination of caloric restriction and deletion of two specific genes might be the key to increasing life span.

"We have about 25 trillion cells in the body, which turn over once every seven years, and the idea that a minor change will significantly increase life span is hard to believe," Buettner said. "It is still so far out."

Instead, he figures the average American could live eight to ten more years if they optimize their lifestyle by taking cues from people in the Blue Zones, such as a plant-based diet, some form of caloric restriction, and regular-intensity physical activity.

Study author Longo, however, argues that a change in a single gene can indeed drastically extend life span.

"Every organism has an ability to detect whether there is food," he said. "If there aren't enough nutrients around—whether you are a mouse or yeast—you have to come up with plan B, and that is to divert all energy into not aging, because you cannot afford to age while you are not reproducing."

The promise of his discovery, Longo said, lies not just in extending life span but also in preventing several major diseases.

If it turns out that the Ecuadorians with the hormone mutation have a lower incidence of cancer, for instance, drugs that decrease growth hormone signaling—which are already on the market—would have the potential to prevent or reduce cancer in families with a history of the disease.

"It is not much different from taking statins to prevent cardiovascular disease," Longo said.

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