Heart failure is one of the most debilitating conditions linked to old age, and there are no specific therapies for the most common form of this condition in the elderly. A study published by Cell Press May 9th in the journal Cell reveals that a blood hormone known as growth differentiation factor 11 (GDF11) declines with age, and old mice injected with this hormone experience a reversal in signs of cardiac aging. The findings shed light on the underlying causes of age-related heart failure and may offer a much-needed strategy for treating this condition in humans.
"There has been evidence that circulating bloodstream factors exist in mammals that can rejuvenate tissues, but they haven't been identified. This study found the first factor like this," says senior study author Richard Lee of the Harvard Stem Cell Institute and Brigham and Women's Hospital.
Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs, causing shortness of breath and fatigue, and it is becoming increasingly prevalent in the elderly. The most common form of age-related heart failure involves thickening of heart muscle tissue. But until now, the molecular causes and potential treatment strategies for this condition have been elusive.
To identify molecules in the blood responsible for age-related heart failure, a team led by Lee and Amy Wagers of the Harvard Stem Cell Institute and Joslin Diabetes Center used a well-established experimental technique: they surgically joined pairs of young and old mice so that their blood circulatory systems merged into one. After being exposed to the blood of young mice, old mice experienced a reversal in the thickening of heart muscle tissue. The researchers then screened the blood for molecules that change with age, discovering that levels of the hormone GDF11 were lower in old mice compared with young mice.
Moreover, old mice treated with GDF11 injections experienced a reversal in signs of cardiac aging. Heart muscle cells became smaller, and the thickness of the heart muscle wall resembled that of young mice. "If some age-related diseases are due to loss of a circulating hormone, then it's possible that restoring levels of that hormone could be beneficial," Wagers says. "We're hoping that some day, age-related human heart failure might be treated this way."
- Francesco S. Loffredo, Matthew L. Steinhauser, Steven M. Jay, Joseph Gannon, James R. Pancoast, Pratyusha Yalamanchi, Manisha Sinha, Claudia Dall’Osso, Danika Khong, Jennifer L. Shadrach, Christine M. Miller, Britta S. Singer, Alex Stewart, Nikolaos Psychogios, Robert E. Gerszten, Adam J. Hartigan, Mi-Jeong Kim, Thomas Serwold, Amy J. Wagers, Richard T. Lee. Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy. Cell, 2013; 153 (4): 828 DOI: 10.1016/j.cell.2013.04.015
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