Circulating Growth Differentiation Factor 11/8 Levels Decline with Age
Rationale: Growth differentiation factor 11 (GDF11) and 8 (GDF8) are members of the TGF-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 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 due 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 nine 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.
- Received September 25, 2015.
- Revision received October 19, 2015.
- Accepted October 21, 2015.