Comparison
Humanin vs. LL-37
Two peptides side-by-side — identity, evidence base, legal status and known adverse events.
Identity
Category
Research other
Research other
CAS no.
330936-69-1
597562-32-8
Molecular weight
2687.27 g/mol
4493.33 g/mol
Half-life
no data
no data
Sequence
Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-AlaLLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTESMechanism of action
Humanin
Humanin arises from a short open reading frame within the 16S rRNA region of the mitochondrial genome (MT-RNR2) — it is therefore not encoded by nuclear DNA. Mechanistically, preclinical work describes a cytoprotective, anti-apoptotic effect via multiple pathways: an extracellular interaction with a trimeric receptor complex of gp130, CNTFR and WSX-1 with downstream activation of JAK2/STAT3 signalling, as well as intracellular interactions including inhibition of the pro-apoptotic protein BAX (and of tBID), binding to IGFBP-3 with modulation of the IGF-1 axis, and interaction with FPRL1/FPRL2 receptors. These models derive predominantly from cell culture and rodents; the extent to which they reflect human physiology after administration of exogenous synthetic humanin is not established by controlled human trials.
LL-37
LL-37 is a cationic, amphipathic helical peptide and the only member of the cathelicidin family in humans. It is generated by proteolytic cleavage from the C-terminal portion of the precursor protein hCAP18 (CAP-18). Mechanistically it associates with and can permeabilize microbial membranes; in addition it modulates immune cells, influences cytokine release, exerts chemotactic activity, and can bind extracellular self-DNA. Preclinical models have described both anti-inflammatory and pro-inflammatory effects, depending on concentration and tissue context.
Evidence base
Highest evidence
Human trial
Human trial
Studies
4
4
of which in humans
1
1
Effects recorded
4
4
Open conflicts
1
1
Documented adverse events
0
0
Legal status
Full entries
Frequently asked questions
- What is the difference between Humanin and LL-37?
- Humanin is classified as "Research other", while LL-37 is classified as "Research other". Humanin: Humanin is a 24-amino-acid mitochondrial-encoded peptide (mitochondrial-derived peptide, MDP) whose open reading frame lies within the 16S rRNA region (gene MT-RNR2) of mitochondrial DNA. It is considered the founding member of the MDP family and was discovered in 2001 by the Hashimoto/Nishimoto group while searching for neuroprotective factors in the brain of an Alzheimer's patient. In basic research (including the laboratory of Pinchas Cohen) humanin is described as a cytoprotective, anti-apoptotic peptide and is studied in the contexts of Alzheimer's/neuroprotection, metabolism/insulin action and aging. The evidence comes almost entirely from cell and animal models and from observations of endogenous levels in humans; controlled human trials of exogenous humanin as a therapeutic are lacking. It is not approved as a medicine anywhere and is traded on the grey market as a research chemical. LL-37: LL-37 is the only known human cathelicidin, a 37-amino-acid antimicrobial peptide generated by cleavage of the precursor protein hCAP18. In research it plays a central role in innate immune defence and wound healing, yet acts in a context-dependent manner as both anti- and pro-inflammatory and has been linked to autoimmune processes. LL-37 is not an approved drug; the evidence base is predominantly basic and preclinical. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, Humanin or LL-37?
- The highest available evidence level is "Human trial" for Humanin and "Human trial" for LL-37. A higher evidence level means more robust data, but says nothing about suitability for an individual. The full body of evidence is on each peptide's own page.
- What is the legal status of Humanin and LL-37 in Germany and the United States?
- Germany: Humanin — Unapproved, LL-37 — Research only. United States: Humanin — Research only, LL-37 — Research only. These are factual summaries with source and review date on the individual pages.