B. D. Colen/Harvard University.
Harvard Stem Cell Institute scientists Richard T. Lee and Amy Wagers have identified a protein that in mice causes old, enlarged, weakened hearts to return to youthful size and function.
A team of Harvard Stem Cell Institute scientists have discovered a protein that circulates in blood that can turn old hearts young, causing a mouse’s heart that has thickened and enlarged with age to revert back to a more youthful state.
The researchers hope that the discovery will lay a foundation for a new approach to therapy for a common form of heart failure that strikes elderly people, although much more research is needed before it could be tested in people.
“The change was unbelievably obvious,” said Dr. Richard T. Lee, a cardiologist at Brigham and Women’s Hospital and one of the leaders of the study, published Thursday in the journal Cell. “Usually we do quite sophisticated quantitative analyses of hearts and the shapes of the cells and things like that. ... You could see what happened from the very first experiment.”
Outside researchers praised the study, which used a decades-old technique of stitching together the circulatory systems of two mice, called parabiosis. In this case, an old mouse was connected to a young mouse—a technique that co-author Amy Wagers, a Harvard stem cell scientist, has utilized to examine the effect of blood on aging in various tissues. The researchers saw that something in the blood of the young mouse had a rejuvenating effect on the older mouse’s heart. Then, they started a systematic hunt for the factor that could be causing the change, ultimately finding that a protein called GDF-11 was the trigger.
“I’m really intrigued by this idea,” said Saul Villeda, a faculty fellow at the University of California, San Francisco. “What I’m interested in is how many [of these factors] will be tissue-specific. Will others be specific for the liver or the brain?”
In 2011, Villeda, who was not involved in the current research, found that blood from old mice could decrease the creation of new brain cells in young mice. Villeda identified a factor in the blood that seemed to be behind the effect, which also impaired learning and memory in young mice.
The Harvard researchers now plan to try and understand whether the protein they’ve identified could be involved in the rejuvenation of other tissue that has been observed when young and old mice share a circulatory system, for example in muscle stem cells.
While the researchers are hopeful that their insight could prove useful against diastolic heart failure in people, a cardiac specialist cautioned that the work, though rigorous and interesting, had not yet made the case that it would have an effect on disease.
“They’ve elucidated a mechanism of normal aging which may, at the level of plausibility, have something to do with heart failure,” said Dr. Eduardo Marbán, director of Cedars-Sinai Heart Institute. He added, “there’s absolutely no demonstration in this paper that GDF-11 will help heart failure, or be involved at all in any disease state. ... This is the beginning of a long road.”
Marbán said that as all people age, their hearts naturally change, with cells getting larger and the muscle walls thickening. But he noted that most of those people never develop heart failure, so it is unclear whether the effect the researchers achieved would be a way to successfully treat heart failure.
Problems may also arise in translating the insight into a drug because the protein is known to be involved in other functions in the body.
Mark Mercola, a professor of engineering at the University of California, San Diego, said that the protein GDF-11 is part of a family of molecules that also affect cells that break down bone. It’s possible, then, that administering the protein could cause a loss of bone density.
“To think about using it as a drug, you also have to think about what it might be doing elsewhere,” Mercola said. “So I think the translation of this is not apparent, but it’s certainly groundbreaking” to show that a molecule can have such profound anti-aging effects on the heart.