Reverse aging? Scientists discover protein that could turn hearts younger

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No matter how young an individual may feel at heart, little can currently be done to counteract the effects of natural cardiovascular aging. As an adults ages, his or her heart grows larger and its walls thicken, often leading to a disease known as diastolic heart failure. This is the most common form of age-related heart failure and despite the fact that it affects millions, there is no known treatment.

However, in a breakthrough discovery, researchers at Harvard University have pinpointed a protein that, when injected into the blood of mice, is able to reverse aging in the heart within 30 days – effectively turning old hearts young again.

“We’ve developed this potentially broadly-acting rejuvenative protein and we are excited to understand its potential in humans,” study author Amy Wagers, a professor of stem cell and regenerative biology at Harvard University, told FoxNews.com.

Wagers and her colleagues identified the protein, known as GDF-11, over many years of research. Because aging occurs more or less uniformly throughout the body, the researchers had long suspected that one specific factor essentially signals to all of the body’s tissues how they should function as a context of age.

“We looked in the blood stream, because the blood carries things to all parts of the body; that would be a logical place for that substance to be traveling,” Wagers said.

Eventually, they zeroed in on the protein GDF-11.

“(The protein) was very high in the blood of young mice and low in the blood of old mice, suggesting that could have an impact on aging,” Wagers said.

After discovering the protein, Wagers and her colleagues decided to study the impact it had on cardiovascular aging. They injected GDF-11 into the blood streams of older mice in order to increase their GDF-11 levels to match the levels found in younger mice.

After 30 days, the researchers examined the hearts of the older mice, which had previously shown thickened walls similar to those in older humans. The researchers found that the thickening had reversed, and the hearts of the older mice now looked almost identical to those of the younger mice.  

“The older hearts really did look almost the same at a gross anatomy level. I’m certain there are still some differences, but it was quite dramatic how much rejuvenation (there was),” Wagers said.

While previous research has shown regenerative treatment through the use of stem cells in spinal and muscular-skeletal systems, Wagers and her team were shocked to discover that a protein could have a regenerative effect on the heart.

“I was very surprised, actually,” Wagers said. “The process I had in my mind was that it was a process of controlling function in normally regenerative tissues and replacing cells all the time.”

Because GDF-11 can be circulated through the blood system, it offers a “very therapeutically accessible opportunity,” Wagers noted.

Researchers estimate that four to five more years of testing and research still needs to be done before clinical trials could begin.  However, Wagers and her colleagues hope to one day use this discovery to help reverse cardiovascular aging in humans as well.

“We hope that by providing this protein, we could reverse that heart enlargement, and that would have a benefit to the many patients who have this form of heart disease,” Wagers said.

This research was published on May 9 in the journal Cell. 

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New nano-'tracking devices' allow doctors to visualize stem cells inside hearts

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Heart stem cell therapy after a major heart attack holds the promise of helping to repair severely damaged cells by encouraging the growth of new ones. However, the process – which involves infusing healthy stem cells into the heart to replace the damaged tissue – has had limited success in clinical trials.

In order to get the most benefit from heart stem cell treatment, it is essential for doctors to properly place the cells in the heart.  But, once the stem cells are injected, it’s difficult to determine exactly where they wind up, and many scientists believe faulty placement is ultimately the culprit of the therapy’s disappointing results.

Now, that problem could be potentially solved with a new visualization technique developed by Dr. Sam Gambhir and fellow researchers at Stanford University School of Medicine in California.  Their study, published in Science Translational Medicine, details the invention of silica nanoparticles, which can be injected inside stem cells, acting as tiny tracking devices that allow doctors to see the stem cells’ path inside the body.

According to the study’s researchers, the most encouraging results from heart stem cell therapy have been seen after bypass surgery, which is done right after a patient has suffered a heart attack.  If performed correctly, stem cell injections can encourage new cell proliferation and help increase blood flow up to 10 percent.

To get the most benefit, doctors have to find the perfect place in which the cells will do the most work.

“The best place is the region (in the heart) between the damaged tissue and the healthy tissue,” Jesse Jokerst, a postdoctoral fellow in the Stanford Molecular Imaging Scholars Program and one of the study’s authors, told FoxNews.com.  “That’s where the most therapeutic benefit can occur. When placed there, the stem cells can take advantage of the blood flow in the healthy region, but can effect a change in the diseased region.”

In order to determine where to place the cells, physicians currently take images of the heart through magnetic resonance imaging (MRI) – one image before the injection to estimate placement, and a second image after the injection to see how the cells have developed. But the time period between the capture of those pictures leaves a lot to be desired, as the stem cells do not have a unique “signature” that allows doctors to differentiate between them and the normal heart cells.

Feeling somewhat blind, the doctors have many questions once the stem cells are injected.  Did they reach their intended target? Did they remain at the heart wall? How many cells actually stayed and how many diffused or died?  Inevitably, the doctors have to wait weeks following the stem cell injection to get their questions “answered,” by observing if heart function improved.  

Making a stem cell 'movie'

Frustrated by those time constraints, the researchers realized all their questions could be answered a lot faster and much more accurately through ultrasound imaging.

“MRI is like taking a photograph,” Jokerst explained.  “But we want to see the cells like in a movie, and that’s what ultrasound allowed us to do.”

The researchers decided to work with a material called silica – a chemical compound somewhat related to glass, which is found in sand and quartz.  After creating silica particles with diameters of just 300 nanometers – one-three-thousandth the width of a human hair – the team injected the tiny silica “trackers” into the stem cells, which easily ingested and stored them without any complications.  The stem cells – which were derived from the hearts of mice, pigs and humans – were then injected into the hearts of healthy mice, where they were observed by the researchers.

As soon as the stem cells left the needle, sound waves from an ultrasound passed through the body.  The silica, which is ideal for backscattering ultrasound waves, caused the waves to bounce back, highlighting where the stem cells were aggregating in the body.

According to Jokerst, the cells appeared much more clearly than they had imagined.

“Luckily, when we put the nanoparticles inside the cells, they aggregated together into larger structures inside of the cellular compartments,” Jokerst said.  “We were prepared to have OK signal, but we were surprised at how dramatic the signal increase was as a result of that aggregation.”

Through this new technique, the team was able to detect as little as 70,000 stem cells through ultrasound and as little as 250,000 through MRI.   The Stanford team has filed for provisional patents for their invention, but they noted this type of imaging wouldn’t be available in humans for at least three to five years.  One of the biggest hurdles the procedure still needs to overcome is biodegradation – making it so the particles degrade to even smaller particles once the imaging is done so that they can be excreted in the urine.

Overall, Jokerst envisions this treatment being used on patients with shortness of breath, congestive heart failure, and most notably, those who have suffered severe heart attacks.  Ideally, patients would benefit from the current imaging technique, and the new more film-like procedure.

“We’ve changed the composition; so not only would we have MRI signal, but also ultrasound signal,” he added.

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