GDF-11

Not a peptide. GDF-11 is a protein of the TGF-β superfamily — a disulphide-linked dimer of two ~12.5 kDa mature chains (about 109 amino acids each) released from a larger precursor. It is included because it is constantly discussed alongside peptides as a "young blood" rejuvenation factor. The same evidence standards apply.

GDF11, growth differentiation factor 11, bone morphogenetic protein 11 (BMP-11)

Longevity & cellular

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Naturally occurring TGF-β-family signalling protein; about 90% identical in its mature domain to myostatin (GDF-8)
Mechanism: Binds activin type II receptors (ActRIIA/B) with ALK4/5/7 and signals through SMAD2/3 — the same pathway as myostatin, which is why its effects on muscle are contested
Routes studied: Daily intraperitoneal injection of recombinant GDF-11 (mice); parabiosis and plasma transfer (mice, as the original "young blood" context); cell culture
Dose range reported: Mice: 0.1 mg/kg/day IP in the original rejuvenation studies (Loffredo 2013; Sinha 2014); 0.1–1 mg/kg in later studies that found muscle atrophy at higher exposures. No human dose exists. Community-reported: microgram-range daily or weekly injections of recombinant protein of unverified identity
Half-life: Not well characterised; recombinant GDF-11 is cleared from mouse plasma within hours; much circulating GDF-11 is in latent complexes
Storage: Recombinant protein: frozen, with carrier protein, avoid freeze–thaw; reconstituted dilute solutions lose activity quickly. Not suited to home handling
Regulatory status: Not approved anywhere; research reagent only

Doses are as reported in studies or by the community — never recommendations.

1What it is

GDF-11 is a developmental signalling protein, essential for patterning the skeleton and organs in the embryo. It became famous in 2013–2014 when a Harvard group reported that it declined with age in mouse blood and that restoring it reversed age-related heart thickening, improved muscle regeneration and strength, and rejuvenated blood vessels and neurogenesis in the aged mouse brain — apparently explaining the earlier "young blood" parabiosis results. Within two years, other laboratories reported the opposite: that GDF-11 did not fall with age (the original assay had cross-reacted with myostatin), did not rescue the ageing heart, and at higher doses caused muscle wasting and weight loss — exactly what one would predict from a myostatin relative.

The result is one of the more instructive controversies in ageing research, and a reason for caution: the "rejuvenation factor" and the "muscle-wasting factor" are the same protein, and the difference appears to be dose, context and assay. It is a natural protein. Products sold as "GDF-11" for self-injection are of unverified identity and activity.

2How it's thought to work

Receptor signalling. GDF-11 binds ActRIIA/ActRIIB with type I receptors ALK4/5/7, activating SMAD2/3. Myostatin uses the same receptors, so the two have overlapping — and partly opposing — reported effects depending on tissue and concentration.

Reported rejuvenation mechanisms (contested). reduced cardiomyocyte hypertrophy via FOXO signalling; improved satellite-cell (muscle stem cell) function and DNA integrity; increased cerebral blood flow and neurogenesis; in later work, increased adiponectin and a calorie-restriction-like metabolic state (Katsimpardi 2020).

Catabolic mechanisms. at supraphysiological exposure GDF-11 activates the same atrophy programme as myostatin — reduced protein synthesis, increased muscle protein breakdown, loss of body weight (Hammers 2017; Egerman 2015).

Circulating GDF-11 is largely bound in latent complexes with its prodomain and with binding proteins such as follistatin, so total level and active level are not the same thing.

GDF-11, a TGF-beta family member closely related to myostatin, signalling through activin receptors. Its level falls with age; whether restoring it rejuvenates tissue is contested, because the assays that first reported the fall could not reliably tell it from myostatin.Schematic — not to scale

3What the research shows

Graded C (contested)

Cardiac rejuvenation in aged mice

Daily GDF-11 for 30 days reversed age-related cardiac hypertrophy in old mice and was associated with reduced hypertrophy markers (Loffredo 2013, Cell). An independent group using the same dose and a different GDF-11 source found no effect on cardiac hypertrophy and no decline in GDF-11 with age (Smith 2015, Circ Res). [1][5]

Graded C (contradictory)

Skeletal muscle in aged mice

Restoring GDF-11 improved satellite-cell function, muscle structure, grip strength and endurance in old mice (Sinha 2014, Science). Other groups then reported that GDF-11 levels rise rather than fall with age, that the original assay cross-detected myostatin, and that GDF-11 inhibits muscle regeneration (Egerman 2015, Cell Metab). Supraphysiological GDF-11 caused striated-muscle atrophy and weight loss in mice (Hammers 2017, EMBO Mol Med). [2][4][7]

Brain vasculature and neurogenesis

GDF-11 increased cerebral blood vessel density and neurogenesis in the aged mouse brain (Katsimpardi 2014, Science). Later mouse work reported anti-depressant-like and pro-neurogenic effects and a calorie-restriction-like metabolic profile (Katsimpardi 2020, Aging Cell). Not independently contradicted as strongly as the muscle data, but not independently replicated at scale either. [3][8]

Graded B (observational, contradictory)

Human circulating levels

In two cardiovascular cohorts, higher combined GDF-11/8 levels were associated with lower risk of cardiovascular events and death (Olson 2015, Eur Heart J). Other cohorts have found no association or associations with frailty. Assays struggle to separate GDF-11 from myostatin, so most human data measure the pair. [6]

Administration to humans

No published trial. Community reports from people injecting recombinant GDF-11 describe effects ranging from "nothing" through "more energy and better skin" to fatigue and weight loss; these are unblinded, product identity is unverified, and the weight-loss reports are consistent with the catabolic mechanism.

4Reported side effects and interactions

Literature-reported

No human data. In mice, higher exposure caused muscle atrophy, cachexia-like weight loss and, in some studies, reduced bone mass — serious outcomes that are mechanistically expected from a myostatin relative.

Community-reported

Fatigue, unexpected weight loss, nausea, injection-site reactions, mood changes; some report improvements in skin and recovery. All anecdotal.

Theoretical. TGF-β-family signalling has roles in fibrosis and in tumour biology (both suppressing and promoting, depending on stage); chronic activation is not something to assume is benign. Immunogenicity of an injected foreign protein.

Interactions. None established. Anything that modulates the myostatin/activin axis (follistatin, ActRII-blocking antibodies in trials) is the relevant class.

Markers researchers commonly monitor

No markers are established for administration. From the mechanism and the mouse data, members commonly discuss:

Marker	Why it's watched
Body weight, lean mass (DEXA or bioimpedance) and grip strength	the muscle-wasting signal in mice is the single most important thing to watch; losses here are a reason to stop.
Serum GDF-11 (research assay)	commercially available ELISAs cross-react with myostatin and are not standardised; results are hard to interpret.
CBC	GDF-11 regulates late-stage red-cell maturation (the basis of the approved drug luspatercept, which traps GDF-11), so haemoglobin is a mechanism-relevant marker.
Lipid panel, fasting glucose, adiponectin	the metabolic claims from the 2020 mouse work.
CMP	general baseline.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Genuine recombinant GDF-11 is a research reagent supplied frozen, often as a dimer that must be in a specific buffer with carrier protein and used quickly; it is not stable for weeks in in a fridge. No home-use preparation is established. The calculator is for mass-to-volume arithmetic on a labelled product only, and says nothing about whether the product is active GDF-11.

Open in calculator, pre-loaded →

6Commonly studied alongside

Klotho (#89) — the other "young blood" protein; follistatin and myostatin inhibitors as the mechanistic counterparts; in community discussion alongside Epitalon (#13), Humanin (#15) and MOTS-c in "longevity stacks", with no combined data. In the literature, young-plasma transfer is the parent intervention.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; research reagent. Not on the compounding bulk-substance lists †
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport (WADA)	Growth factors and their modulators are prohibited under S2; GDF-11 fits that class †, and S0 applies regardless

8Open questions

Does GDF-11 rise or fall with age in humans? The assays still cannot cleanly separate it from myostatin.
Is there any dose window in which benefits appear without muscle loss, and does it exist in humans?
Are the brain and vascular findings reproducible in independent hands?
Do any products sold as GDF-11 contain active dimeric protein? No independent analysis is published.

9References

1Loffredo FS et al. (2013). Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell. PubMed · DOI
2Sinha M et al. (2014). Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science. PubMed · DOI
3Katsimpardi L et al. (2014). Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science. PubMed · DOI
4Egerman MA et al. (2015). GDF11 increases with age and inhibits skeletal muscle regeneration. Cell Metab. PubMed · DOI
5Smith SC et al. (2015). GDF11 does not rescue aging-related pathological hypertrophy. Circ Res. PubMed · DOI
6Olson KA et al. (2015). Association of growth and differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts. Eur Heart J. PubMed · DOI
7Hammers DW et al. (2017). Supraphysiological levels of GDF11 induce striated muscle atrophy. EMBO Mol Med. PubMed · DOI
8Katsimpardi L et al. (2020). Systemic GDF11 stimulates the secretion of adiponectin and induces a calorie restriction-like phenotype in aged mice. Aging Cell. PubMed · DOI

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

26 Oct 2026Profile published — awaiting medical review

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