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Protein Rejuvenates Hearts In Mice

Researchers in the US have identified a protein that rejuvenates old hearts in mice. The mouse hearts had thickened walls, a sign of aging similar to that seen in humans, but after treatment their hearts reduced in size and thickness, and became more like the hearts of younger mice.

The researchers suggest the protein, known as growth differentiation factor 11 (GDF-11), may prove to be the first effective treatment for a form of age-related heart failure, called diastolic heart failure, that affects millions of Americans and often involves thickening of the heart muscle (cardiac hypertrophy) in the elderly.

Led by two Harvard professors, stem cell biologist Amy Wagers, and practising cardiologist Richard T. Lee, the team writes about its findings in a paper published online in the journal Cell on 9 May.

Lee, who is a Harvard Medical School professor at Brigham and Women's Hospital in Boston and a principal faculty member at Harvard Stem Cell Institute (HSCI), says in a statement:

"The most common form of heart failure [in the elderly] is actually a form that's not caused by heart attacks but is very much related to the heart aging."

Referring to the study as "the coolest thing I've ever been a part of", Lee says that giving GDF-11 to older mice appeared to reverse heart aging in a very short period of time.

"We are very excited about it because it opens a new window on the most common form of heart failure," he adds.

Lee says about 20 of his 300 patients have diastolic heart failure. Currently their treatment consists of coming to the hospital and having a lot of fluid taken off, then going home. Then they come back again and do the whole thing again.

He says the lack of drugs to treat this condition is "very frustrating".

"We need to work as hard as we can to figure out if this discovery can be turned into a treatment for heart failure in our aging patients," he urges. The Discovery Could Hugely Revise Our Understanding of Aging The team believes that perhaps even more important than what they mean for the treatment of diastolic heart failure, their findings may hugely revise our understanding of aging.

In her lab, Wagers, a professor in Harvard's Department of Stem Cell and Regenerative Biology, and like Lee, also a a principal faculty member at HSCI, works with parabiotic mouse systems, where mice share a circulatory system. These have already shown that factors present in the blood of young mice appear to rejuvenate tissue, particularly of the spinal cord and muscles, in older mice.

Wagers says aging is accompanied by many changes in the body that are often tied to decline in function.

"One of the interests of my laboratory is in understanding why this happens and whether it is an inevitable consequence of aging, or if it might be reversible," she adds.

She says their interest in GDF-11, the journey described in the current study, started when she, Lee and the team compared young and old animals and found a factor in the blood that is present in high quantities in youth, and in low quantities in old age.

"We further found that when we supplemented the low levels of this substance that were present in old animals to the levels normally seen in youth, this could have a dramatic effect on the heart," Wagers explains.

Lee and Wagers are now working on taking GDF-11 into clinical trials, which Lee suggests will start in about four or five years time. They are also trying to find out which other types of tissue the protein might act on. Finding GDF-11 Was A Gradual Process of Elimination Wagers says that for some time now scientists have observed that aging occurs more or less at the same time throughout the body, as if it is synchronized in some way, and this points to a common signal driving the body's response to aging.

"We hypothesized that this common signal might be a substance that was traveling in the bloodstream, because the bloodstream accesses organs throughout the body," she adds.

One of the challenges was to show that in the parabiotic mouse system it wasn't just that the young mice were causing the blood pressure to go down in the old mice (high blood pressure is a known cause of heart wall thickening).

Lee says they "had to build a custom device to measure blood pressures off their tails. It took a year to do the analysis to show that it was not a blood pressure effect."

It took about two and a half years of this type of work to convince them that they really had to identify the factor.

"It took about six months to find something, and another year to be convinced that it was real," says Lee.

They looked at lipids, and they looked at metabolites. They found GDF-11 after setting up a collaboration with a company that specializes in analyzing factors in blood.

GDF-11 belongs to a family of around 35 proteins called TGF-beta (transforming growth factors).

"Some have been very well studied, and this is one that is relatively obscure," says Lee.

Funds from HSCI, the National Institutes of Health, and the American Heart Association helped finance the study.

In another recent study, researchers at the University of Leicester discovered a link between fast biological aging and the risk of developing many age-related diseases and various cancers. In this case the link is related to telomeres, which are found at the end of chromosomes.

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