麻豆传媒

Mice with age-related heart failure but preserved systolic function regained a youthful heart when given a protein extracted from the blood of young mice, researchers found.

At first, researchers observed a "stunning" reversal of cardiac hypertrophy when young and old mice shared blood circulation, but were unable to pinpoint the blood component responsible for the change, according to Richard T. Lee, MD, of Harvard Medical School and Brigham and Women's Hospital, and colleagues.

After several years of searching, however, they identified GDF (growth differentiation factor)-11 as the protein that relatively quickly gave old hearts new life and injected it into the older animals, they reported in the journal Cell.

"The changes to the hypertrophic hearts were so dramatic that they could be seen with the naked eye," Lee said during a press conference.

"Heart failure with preserved systolic function, also called diastolic heart failure, is one of the most frustrating diseases cardiologists face because there are no successful therapies," Lee said. "But the initial experiments with GDF-11 were stunningly positive from the outset."

GDF-11, which belongs to the TGF (transformational growth factor)-beta superfamily, declines with age. As it does, ventricular "stiffening" slowly takes place, eventually leading to heart failure with preserved systolic function.

But "emerging evidence indicates that systemic factors profoundly influence tissue aging," researchers wrote.

Some of this evidence has come from experiments using a process called parabiosis -- where two mice are surgically joined so that they share blood circulation.

Co-author Amy Wagers, PhD, a professor in Harvard's department of stem cell and regenerative biology, had previously shown that factors in the blood of young animals, which until now were unidentified, have a rejuvenating effect upon various tissues in older animals, particularly in the spinal cord and musculature.

"One of the interests of my laboratory is in understanding why a decline in the function of our bodies happens and whether it is an inevitable consequence of aging, or if it might be reversible," Wagers said at the press conference.

In the present study, Wagers said, they identified a substance in the blood that is abundant in youth and lower in the elderly.

"We further found that when we supplemented the low levels of this substance that were present in old animals to the levels normally seen in youth, this could have a dramatic effect on the heart."

One precaution researchers took was to determine whether the change in the aging hearts had anything to do with a reduction in blood pressure.

They worked for a year, using a custom-built apparatus to measure blood pressure off the tails of mice, before they could conclude that the change in the heart's shape and size was not the result of lowered blood pressure.

Researchers have not investigated yet whether the morphological cardiac change correlates with a longer life span.

However, they intend to examine the effect of GDF-11 in other organ systems, and eventually will test the protein in humans.

They also noted that GDF-11 may not be the only protein or factor with anti-hypertrophic properties.

From the American Heart Association:

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