Two Harvard Stem Cell Institute (HSCI) researchers — a stem cell biologist and a practicing cardiologist at Brigham and Women’s Hospital — have identified a protein in the blood of mice and humans that may prove to be the first effective treatment for the form of age-related heart failure that affects millions of Americans.
When the protein, called GDF-11, was injected into old mice, which develop thickened heart walls in a manner similar to aging humans, the hearts were reduced in size and thickness, resembling the healthy hearts of younger mice.
Even more important than the implications for the treatment of diastolic heart failure, the finding by Richard T. Lee, a Harvard Medical Schoolprofessor at the hospital, and Amy Wagers, a professor in Harvard’sDepartment of Stem Cell and Regenerative Biology, ultimately may rewrite our understanding of aging.
“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,” said Lee, who, like Wagers, is a principal faculty member at HSCI.
“In this study, we were able to show that a protein that circulates in the blood is related to this aging process, and if we gave older mice this protein, we could reverse the heart aging in a very short period of time,” Lee said. “We are very excited about it because it opens a new window on the most common form of heart failure.”
“The blood is full of all kinds of things,” the biologist said, “and trying to narrow down what might be the responsible factor was going to be a big challenge. I think that’s where the collaboration was so wonderful, in that we could take advantage of the expertise in both of our laboratories to really home in on what might be the responsible substance.”
Lee explained, “We thought it was interesting right away, and we repeated it right away. But we had to show that this was not a blood pressure effect, that the young mice didn’t just cause the old mice to have lower blood pressure. We 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.
“After about 2½ years we were convinced, and said, ‘We really have to identify this factor.’ It took about six months to find something, and another year to be convinced that it was real,” Lee said. “We looked at lipids; we looked at metabolites. Then we set up a collaboration with a startup company in Colorado, called SomaLogic, that had an interesting technology for analyzing factors in blood. And by working closely with SomaLogic, we found the likely factor.”
What the researchers found was that at least one of the factors causing the rejuvenation of the hearts was GDF-11, “a member of a very important family of proteins called TGF-beta proteins, for transforming growth factor. There are around 35 members of the family,” Lee said. “Some have been very well studied, and this is one that is relatively obscure.”