Author/Authors :
Francesco S. Loffredo، نويسنده , , Matthew L. Steinhauser، نويسنده , , Steven M. Jay، نويسنده , , Joseph Gannon، نويسنده , , James R. Pancoast، نويسنده , , Pratyusha Yalamanchi، نويسنده , , Manisha Sinha، نويسنده , , Claudia Dall’Osso، نويسنده , , Danika Khong، نويسنده , , Jennifer L. Shadrach، نويسنده , , Christine M. Miller، نويسنده , , Britta S. Singer، نويسنده , , Alex Stewart، نويسنده , , Nikolaos Psychogios، نويسنده , , Robert E. Gerszten، نويسنده , , Adam J. Hartigan، نويسنده , , Mi-Jeong Kim، نويسنده , , Thomas Serwold، نويسنده , , Amy J. Wagers، نويسنده , , Richard T. Lee، نويسنده , , et al.، نويسنده ,
Abstract :
The 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-β 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.
