

Scientists say they've found a new explanation – and a perhaps a path to a new cure – for heart disease.

In a study published today in Science, researchers led by UCLA molecular medicine professor Douglas Wallace modified a single mitochondrial gene in mice.

Their hearts quickly wore out and broke down.

Mitochondrial defects, which accumulate naturally during the course of a lifetime, have previously been found in diseased human heart tissue. However, it wasn't clear whether the defects were a cause or an effect of heart disease. The UCLA findings offer direct evidence of a causal connection.

By finding ways to rejuvenate or protect these cellular power generators, it may be possible to prevent heart disease, which kills over 600,000 Americans every year – and that could be just the start.

"This provides strong support for the concept that aging and age-related diseases are associated with a decline in mitochondrial functional associated with the age-related destruction of mitochondrial DNA," said Wallace in an email.

Mitochondria are structures called organelles, separate from the

DNA-containing cell nucleus but vital to cellular functioning. They convert chemical energy provided by the food we eat into a form usable by our cells.

The process goes on constantly in every cell in our bodies, but over time the parts run down. Stray oxygen molecules with an especially unstable configuration latch on to DNA in both the nucleus and, more dangerously, in mitochondria themselves.

Mitochondria have their own genes – just seventeen altogether, but of paramount importance, and just a few mutations can cause malfunction, even shutdown.

To model the effects of this degeneration, the researchers added a mutation to mitochondria in a mouse egg. Once fertilized, the egg developed into a mouse riddled with defective mitochondria and, it turned out, defective hearts.

Compared to normal mice, their cardiac tissue was thick and weak, robbed of its natural strength – the same problems found in human heart disease. The mice developed their disease after just a year; normal mice don't have heart problems until they're at least two years old, said Wallace.

As with any rodent study, certain caveats are required, but other scientists have found high mitochondrial mutation rates in diseased human hearts. The* Science* study fits with those findings, suggesting that the connection is direct.

Even more tantalizingly, Wallace and other mitochondrial medicine researchers believe that other age-related diseases, from diabetes and

Alzheimer's to cancer, have the same mitochondrial roots.

They're now searching for ways of fixing that damage with mitochondria-targeting drugs. Among these are resveratrol, a compound that's gained notoriety among longevity hackers and was recently shown to prevent diabetes in mice.

If the drugs work, they could change the way people live – and die.

And if they make it from the lab to people, things really get interesting: who owns them?

A Mouse Model of Mitochondrial Disease Reveals Germline Selection Against Severe mtDNA Mutations [Science]

Image: Normal mouse heart function measurements and tissue samples in the left column; mitochondrially tweaked mice at right.

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