The key is to lower protein-production in cells, which is why eating less can cause lifespan extension. According to the University of Washington:

In this project, the UW researchers studied many different strains of yeast cells that had lower protein production. They found that mutations to the ribosome, the cell's protein factory, sometimes led to increased life span. Ribosomes are made up of two parts — the large and small subunits — and the researchers tried to isolate the life-span-related mutation to one of those parts.

"What we noticed right away was that the long-lived strains always had mutations in the large ribosomal subunit and never in the small subunit," said the study's lead author, Kristan Steffen, a graduate student in the UW Department of Biochemistry.

The researchers also tested a drug called diazaborine, which specifically interferes with synthesis of the ribosomes' large subunits, but not small subunits, and found that treating cells with the drug made them live about 50 percent longer than untreated cells. Using a series of genetic tests, the scientists then showed that depletion of the ribosomes' large subunits was likely to be increasing life span by a mechanism related to dietary restriction — the TOR signaling pathway.

Researchers Uncover Details About How Dietary Restriction Slows Down Aging [Eurekalert]

According to an announcement from PLoS Genetics:

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. "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.

I've always been a skeptic when it comes to life-extending research, but this has me rethinking my position.

Lifespan Extension [PLoS Genetics]