1. Circulating Growth Differentiation Factor 11/8 Levels Decline With Age
- Author
-
Jill M. Goldstein, Emilia Gonzalez, Miook Cho, Tommaso Poggioli, Aysu Uygur, Amy J. Wagers, Claudio Macias-Trevino, Francesco S. Loffredo, Ryan G. Walker, Rachel M Tandias, Peiguo Yang, Ana Vujic, Richard T. Lee, James R. Pancoast, Yick W. Fong, Thomas B. Thompson, Poggioli, Tommaso, Vujic, Ana, Yang, Peiguo, MacIas-Trevino, Claudio, Uygur, Aysu, Loffredo, Francesco S., Pancoast, James R., Cho, Miook, Goldstein, Jill, Tandias, Rachel M., Gonzalez, Emilia, Walker, Ryan G., Thompson, Thomas B., Wagers, Amy J., Fong, Yick W., and Lee, Richard T.
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Aging ,Physiology ,SMAD ,Myostatin ,Biology ,Bone morphogenetic protein ,Horse ,03 medical and health sciences ,Gdf11 protein, mouse ,Mice ,0302 clinical medicine ,In vivo ,Internal medicine ,medicine ,Animals ,Horses ,Mice, Knockout ,Sheep ,Animal ,Bone Morphogenetic Protein ,Growth differentiation factor ,transforming growth factor-β ,Biomarker ,Rats ,Growth Differentiation Factors ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,intercellular signaling peptides and protein ,Growth Differentiation Factor ,Mstn protein, mouse ,GDF11 ,Bone Morphogenetic Proteins ,biology.protein ,Rat ,Antibody ,Cardiology and Cardiovascular Medicine ,030217 neurology & neurosurgery ,Biomarkers ,Transforming growth factor - Abstract
Rationale: Growth differentiation factor 11 (GDF11) and GDF8 are members of the transforming growth factor-β superfamily sharing 89% protein sequence homology. We have previously shown that circulating GDF11 levels decrease with age in mice. However, a recent study by Egerman et al reported that GDF11/8 levels increase with age in mouse serum. Objective: Here, we clarify the direction of change of circulating GDF11/8 levels with age and investigate the effects of GDF11 administration on the murine heart. Methods and Results: We validated our previous finding that circulating levels of GDF11/8 decline with age in mice, rats, horses, and sheep. Furthermore, we showed by Western analysis that the apparent age-dependent increase in GDF11 levels, as reported by Egerman et al, is attributable to cross-reactivity of the anti-GDF11 antibody with immunoglobulin, which is known to increase with age. GDF11 administration in mice rapidly activated SMAD2 and SMAD3 signaling in myocardium in vivo and decreased cardiac mass in both young (2-month-old) and old (22-month-old) mice in a dose-dependent manner after only 9 days. Conclusions: Our study confirms an age-dependent decline in serum GDF11/8 levels in multiple mammalian species and that exogenous GDF11 rapidly activates SMAD signaling and reduces cardiomyocyte size. Unraveling the molecular basis for the age-dependent decline in GDF11/8 could yield insight into age-dependent cardiac pathologies.
- Published
- 2015