Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy
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, 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
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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Figures
![Figure 1. Heterochronic parabiosis reverses age-related cardiac…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3677132/bin/nihms465691f1.jpg)
![Figure 2. Reversal of age-related cardiomyocyte hypertrophy…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3677132/bin/nihms465691f2.jpg)
![Figure 3. Reversal of cardiac hypertrophy in…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3677132/bin/nihms465691f3.jpg)
Figure 4. Differences in blood pressure between…
Figure 4. Differences in blood pressure between young CD45.1 and CD45.2 mice do not explain…
Figure 5. Molecular evidence for remodeling of…
Figure 5. Molecular evidence for remodeling of aged myocardium by a young systemic circulation
ANP…
Figure 6. Heterochronic sham parabiosis does not…
Figure 6. Heterochronic sham parabiosis does not reverse cardiac hypertrophy in aged mice
(A). Flow…
Figure 7. Circulating levels of GDF11 are…
Figure 7. Circulating levels of GDF11 are reduced in aged mice and restoring GDF11 to…
![Figure 4. Differences in blood pressure between…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3677132/bin/nihms465691f4.jpg)
![Figure 5. Molecular evidence for remodeling of…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3677132/bin/nihms465691f5.jpg)
![Figure 6. Heterochronic sham parabiosis does not…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3677132/bin/nihms465691f6.jpg)
![Figure 7. Circulating levels of GDF11 are…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3677132/bin/nihms465691f7.jpg)
Source: PubMed