GDF-11 and Myostatin Correlate with Heart Disease Outcomes

Here researchers study natural variations in GDF-11 and myostatin levels, finding correlations with health outcomes in heart disease patients. This is one of a number of lines of research emerging from the search for cell signals that differ between old and young tissues, and that might be altered to induce old cell populations to behave more like young cell populations despite the damage they have suffered. In recent years researchers have demonstrated the use of GDF-11 to spur greater levels tissue maintenance in aged mice, for example:

Individuals previously diagnosed with heart disease may be less likely to experience heart failure, heart attacks, or stroke, or to die from these events, if they have higher blood levels of two very closely related proteins. One of these proteins, known as GDF11, has attracted great interest since 2013, when researchers showed that it could rejuvenate old mice. Based on these findings, scientists have speculated that drugs that increase GDF11 levels might reverse physiological manifestations of aging that lead to heart failure in people.

The study population included 1,899 men and women with heart disease who ranged in age from 40 to 85 (average 69 years). Because they already had been diagnosed with stable ischemic heart disease, in which blood supply to the heart is reduced due to coronary artery disease, the participants were at elevated risk for stroke, heart attack, hospitalization for heart failure, and death. Hundreds of the participants experienced one or more of these outcomes during the course of the study, in which they were monitored for nearly nine years.

Researchers used a lab test to measure combined blood levels of GDF11 and a very similar protein called myostatin - the test could not distinguish between the two, because they are quite similar both structurally and functionally. The scientists determined that research subjects who had relatively high blood levels of these two proteins at the beginning of the study - in the top 25 percent of all participants - were less than half as likely to die from any cause, in comparison to participants whose blood levels ranked them in the bottom 25 percent. Those in the highest 25 percent also experienced fewer adverse health events associated with heart disease. "We also found that combined levels of GDF11 and myostatin in humans decline with advancing age, but that the rate of this decline varies among individuals."

In mouse studies published in 2013 researchers found that four weeks of GDF11 treatment in old mice that restored the youthful level of this protein reversed potentially harmful thickening of heart muscle. In humans this thickening of heart muscle, known as ventricular hypertrophy, is associated with aging and contributes to heart failure and death. In the new study, the researchers used standard clinical imaging tests to measure ventricular hypertrophy and found that participants with lower levels of the GDF11 and myostatin proteins were more prone to having thickened heart muscle. "This association with less ventricular hypertrophy and death suggests the possibility that GDF11 might act similarly in humans as in mice. Restoring GDF11 or myostatin to their higher, youthful levels might potentially serve as a so-called 'fountain-of-youth' treatment, but far more work remains to be done,"

Link: https://www.ucsf.edu/news/2015/08/131386/study-fountain-youth-protein-points-possible-human-health-benefit

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