GDF11
⚠ Not a peptide — a 12 kDa TGF-β superfamily protein. Rose to prominence through Amy Wagers' 2013–2014 parabiosis studies suggesting it was a "youthful factor" that could reverse cardiac, skeletal muscle, and neural aging in mice. Subsequent independent work substantially walked back or contradicted several of the original claims, and the current consensus view is that GDF11's role in aging is considerably more complex and less uniformly "rejuvenating" than early reports suggested.
A mature 109-amino-acid (~12 kDa) protein in the TGF-β superfamily that became central to rejuvenation research after a series of 2013–2014 papers from Amy Wagers' group and collaborators reported that restoring youthful GDF11 levels to old mice could reverse cardiac hypertrophy, improve skeletal muscle regeneration, and enhance hippocampal neurogenesis. Subsequent work from Novartis and other groups challenged both the assay specificity (GDF11 and the related myostatin/GDF8 cross-react in most commercial assays) and the phenotypic claims. The field has not converged on a unified view: GDF11 likely has context-dependent roles in tissue homeostasis and aging that were initially oversimplified. Included in the encyclopedia as a longevity-adjacent compound commonly discussed in aging and grey-market contexts, with the caveat that it is a protein rather than a short peptide and that the scientific consensus on its "rejuvenating" properties is contested.
Mechanism of action
Binds the activin type II receptors (ActRIIA, ActRIIB) and the ALK4/5/7 type I receptors, activating SMAD2/3 signaling — the canonical TGF-β superfamily pathway shared with myostatin (GDF8). Because GDF11 and myostatin share very high sequence identity in their mature domains, their biological roles have been difficult to disentangle, and much of the controversy about "GDF11 as a youthful factor" traces to cross-reactivity issues in assays and to differences between in-vivo tissue context and in-vitro activity.
Primary uses
- Aging and rejuvenation research (preclinical; contested)
- Cardiac hypertrophy research (preclinical)
- TGF-β superfamily biology
Typical dosing
⚠ No human dosing established. Rodent rejuvenation studies used 0.1–1 mg/kg daily intraperitoneal recombinant GDF11. Any human use would be entirely unregulated and unsupported by any clinical evidence, and would raise substantial safety concerns given GDF11's myostatin-family signaling and potential effects on skeletal muscle mass and cardiovascular remodeling.
Regulatory status
Not FDA-approved. Not in any registered human clinical trial. Research reagent only; available from recombinant-protein vendors.
References
- [pubmed] Loffredo FS, et al. "Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy." Cell, 2013;153:828-839 (original parabiosis paper).
- [pubmed] Egerman MA, et al. "GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration." Cell Metab, 2015;22:164-174 (Novartis counter-paper reporting opposite direction of effect).
- [pubmed] Schafer MJ, et al. "Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease." Cell Metab, 2016;23:1207-1215 (assay specificity critique).
Related peptides
This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.