Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy
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Jay, Steven M.
Pancoast, James R.
Singer, Britta S.
Hartigan, Adam J.
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CitationLoffredo, Francesco S., Matthew L. Steinhauser, Steven M. Jay, Joseph Gannon, James R. Pancoast, Pratyusha Yalamanchi, Manisha Sinha, et al. 2013. “Growth Differentiation Factor 11 Is a Circulating Factor That Reverses Age-Related Cardiac Hypertrophy.” Cell 153 (4) (May): 828–839.
AbstractThe most common form of heart failure occurs with normal systolic function and often involves cardiac
hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging,
we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in
which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the
circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by
reduced cardiomyocyte size and molecular remodeling. Reversal of age-related hypertrophy was not
attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor.
Using modified aptamer-based proteomics, we identified the TGF-b superfamily member GDF11 as a
circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to
youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a
therapeutic opportunity for cardiac aging.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13362665
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