Longevity link found in gene Jackson lab scientist leads research team

A team of scientists led by a Jackson Laboratory researcher has discovered a single gene in a strain of dwarf mice that can extend life dramatically.

The finding is important because it is the first time such a gene has been isolated in mice, mammals that are genetically similar to humans.

When present, the gene can extend life for mice by as much as 25 to 50 percent, and delay the onset of aging, reported the team, which also included scientists from the University of Michigan and the University of Texas.

The first such finding in mammals, the research was published Tuesday in Proceedings of the National Academy of Sciences.

Experts hail the finding as one more step toward understanding the mechanisms of human aging.

“I think it’s really quite important,” said Thomas E. Johnson, an associate professor at the University of Colorado at Boulder’s Institute for Behavioral Genetics. “It’s one of about four studies that showed we can find genes that result in longevity extensions in vertebrates.”

In 1989, Johnson found that a nematode’s life could be extended by 60 percent by mutating a gene. He said the latest finding is particularly important because of the similarity in the genetic structure of mice and humans.

“I pretty much believe that anything that works in the mouse works in humans,” he said.

Scientists continue to work on creating drug therapies based on genetic discoveries. Johnson said it’s difficult to know when the detection of the Pit1 gene in the brown mouse will lead to the discovery of drugs for humans that will mimic the action of mutation and slowing aging. He said it probably would be more than five years, but certainly by the end of the century.

Any such therapy would likely improve the quality of life, not prolong it when someone is ill, Johnson said. “It’s just not possible to extend a debilitated life system even if you wanted to,” he said.

The study, led by Kevin Flurkey of The Jackson Laboratory in Bar Harbor, arrived at some surprising conclusions about the mutant brown mouse strain, which was first described in a journal by a Jackson lab researcher in 1929.

The mouse, called a Snell dwarf, was long thought to have a short life span, but that was largely because of poor resistance to infection. Once the mice were placed in a controlled environment, they were seen to live 25 to 50 percent longer than typical brown mice.

The researchers isolated Pit1 as the gene that produces dwarfism in the strain. The gene impairs the pituitary gland, lowering thyroid, growth and prolactin hormones.

In another brown-mouse variant, called a little dwarf, life span was 20 to 25 percent more than in typical brown mice. Because little dwarfs are deficient only in growth hormone, that substance may play a particularly crucial role in how mice age, the researchers believe.

Jackson spokesman David Premo notes that scientists have known since 1935 that a restricted-calorie diet, in some cases, can extend a mouse’s life by as much as 30 percent. It was surprising, therefore, when the team discovered that Snell dwarfs allowed to eat themselves into obesity – they look like brown billiard balls with noses, according to Premo – also enjoy a longer life expectancy related to their genetic mutation.

Flurkey plans to study whether Snell dwarfs placed on a restrictive diet live longer than other Snell dwarfs, Premo said. Flurkey was unavailable for comment Wednesday.

As scientists work to uncover the mechanisms of aging, researchers hope to find out how long humans can live. Various theories are being tested.

“I don’t think we know enough yet [to say],” Johnson said.