Genetic mutations that accumulate in the DNA of mitochondria—the power plants in cells—determine the lifespan of mice, confirming a cause of aging and suggesting ways to slow it down.

The findings, by researchers at the Karolinska Institute in Stockholm, Sweden, reveal a fundamental biological mechanism underlying the aging process.

"It seems to be a universal phenomenon in mammals that you have this damage to mitochondrial DNA as you get older," says Karolinska researcher Nils-Goran Larsson. "But I and many others thought this was just a secondary phenomenon. I think the importance of our paper is that we actually show these mutations can indeed cause several changes associated with aging."

Cause and effect

Mitochondria convert energy from food to ATP, which cells use for power.

They have their own DNA, called mitochondrial DNA, and researchers have hypothesized that mutations in this contribute to aging by interfering with how cells generate energy.

Previous research has shown that defects in mitochondrial DNA accumulate with age, but it wasn't clear whether such defects were a cause or a symptom of aging.

"What we have now is this clear-cut cause-and-effect relationship," Larsson said in an interview. "It will provide a completely new angle to treat aging-related problems."

Mutated mice

For their study, the researchers used mice genetically engineered to have a defective version of an enzyme responsible for maintaining mitochondrial DNA.

These mice lived an average of 10 to 12 months. Normal mice typically live a little over two years.

The engineered mice also developed several typical signs of premature aging, such as osteoporosis, weight loss, hair loss, anemia, reduced fertility and heart disease.

"But that does not mean all aging is caused by mutations in mitochondrial DNA," says David Finkelstein of the US National Institute on Aging.

Piece of the puzzle

Indeed, beyond damaged mitochondria, research has linked the shortening of telomeres—DNA sequences that cap the ends of chromosomes—to aging.

Other researchers point to the free radical theory as an aging explanation. Free radicals are unstable oxygen molecules that can damage DNA and other cellular structures.

Since mitochondria also generate free radicals, the latest work may further this theory.

Larsson and colleagues say their next steps will be to investigate how damaged mitochondria relate to other possible causes of aging.

The research is reported in the journal Nature