Young blood cures aged hearts

age increases cardiac hypertrophy

Young blood can reverse age-related heart disease in mice. Maybe vampires had the right idea.

As we age, the chance of developing heart disease increases dramatically. Heart disease is the number one killer worldwide. Older people are much more likely to have thickened hearts with bigger cells – a condition called hypertrophy. Hypertrophied hearts do not work as well as normal hearts and so people with heart hypertrophy can develop other heart diseases like heart failure and stroke.

Unfortunately we don’t have a good way to prevent or treat most heart diseases. Scientists are madly studying ageing and heart disease to try and work out how genes levels and cellular messages change in diseased hearts. The hope is that once we know how cells and tissues change, we can stop these changes and thus treat the disease.

One research group has taken an entirely different approach and used blood from young mice to treat heart hypertrophy in old mice. To do this they literally stitched each old mouse to a young mouse. The mice essentially become one mouse, with two hearts pumping shared blood around both bodies. This macabre surgery is called parabiosis and was first done in the 1800s.

The franken-mice were kept stitched together for four weeks. During this time they shared 90% of their blood. And the young blood actually reversed some of the heart hypertrophy in the old mice. Treated old mice had less heart thickening that untreated mice, and their heart muscle cells were the same size as cells from young mice.

Human patients and mice with heart hypertrophy have changed levels of several molecules in their blood. These molecules are called ‘markers of hypertrophy’. The old franken-mice had less changes in three of these markers (ANP, BNP and Serca2) than untreated mice.

Some young and old control mice were stitched together, but their skin was left intact, so they couldn’t form a shared circulation. The hearts of these old pseudo-franken-mice were just as thickened as untreated old mice. So the young blood was the key to treating the old hearts.

The scientists analysed the young blood to try and work out what was treating the old heart disease. They found that there was much more of a molecule called GDF11 in young blood than in old blood. And there was more GDF11 in old franken-mice than in old untreated mice.

So they treated different old mice with either saline or GDF11 for 30 days. Mice treated with GDF11 had significantly smaller hearts and heart muscle cells than mice treated with saline. They also had less changes in the molecular markers of hypertrophy.

The scientists then tested whether GDF11 could prevent hypertrophy in young mice that had constricted arteries. These mice are used as a model to study heart hypertrophy caused by high blood pressure. GDF11 did not prevent hypertrophy in these mice. This means either that GDF11 specifically treats age-related heart hypertrophy, or that it cannot treat hypertrophy caused by high blood pressure.

The next step is to work out whether GDF11 levels are higher in young people than old people. If they are, GDF11 might also treat age-related heart hypertrophy in humans.

The Scientific Paper:
Loffredo et al. Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy. Cell. 2013.

 

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