Growth Differentiation Factor 11 is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy

By F. Loffredo, M. Steinhauser, S. Jay, Joseph Gannon, James R. Pancoast, Pratyusha Yalamanchi, M. Sinha, C. Dall’Osso, D. Khong, J. Shadrach and 10 more. Cell, 2013

905 citations recorded by the source corpus.

Summary 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 TGFβ 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 new therapeutic opportunity for cardiac aging.

Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/d30e06feb496056a1200e13d2fb8c3621b353c49

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Rheumatology

J. Campisi

Citations in the corpus

TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. (2016, background): “Recently, GDF-11 has been identified as a circulating factor in young mice, which reverses age-related dysfunction in mouse cardiac and skeletal muscle (Loffredo et al. 2013; Sinha et al. 2014).”
Measuring biological age using omics data (2022, background): “Studies on hetero-chronic parabiosis and plasma exchange in animals have demonstrated that circulating proteins can have a causal influence on ageing phenotypes across the body, including in skeletal muscle 107,108 , heart 109 and brain 15,110–112 .”
The hallmarks of aging. (2013, background): “…in this regard are the DR approaches to extend healthy lifespan (Piper et al., 2011; Sanchez-Roman et al., 2012) and the rejuvenation strategies based on the use of blood-borne systemic factors identified in parabiosis experiments (Conboy et al., 2005; Loffredo et al., 2013; Villeda et al., 2011).”
Hallmarks of Cellular Senescence. (2018, neutral): “In normal aging, the decline in growth factors, such as GDF11, might also contribute to the activation of mTORC1 and the hypertrophy observed, particularly in cardiac cells [114].”
Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. (2014, background): “Three prominent examples are the ability of a young blood supply to rejuvenate tissue repair in aged skeletal muscle (25) and the capability of young serum to rejuvenate the proliferative and differentiation capacity of human muscle stem cells (satellite cells) from old donors (26), the ability of s”
Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal (2014, background): “Although decreased TGFb signaling has been implicated in aging of cardiac and neural tissue (Blaney Davidson et al., 2005; Loffredo et al., 2013), we observed genes involved in specific signaling modules that are most likely mediating the altered TGF-b response.”