Humanin

Molecular identity

Sequence

Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala

Formula

C119H204N34O32S2

Molecular weight

2687.2 g/mol

CAS

330936-69-1

PubChem CID

16131438

What it acts on

• IGFBP-3 and the IGF-I axis — the peptide is reported to bind IGFBP-3 and to lower circulating IGF-I, while IGF-I in turn appears to regulate peptide levels; the review authors state the mechanism of this reciprocal regulation has still to be elucidated.
• Cell-death signalling — described in the founding literature as an antagonising factor against neuronal death induced by Alzheimer-associated insults, working through multiple intracellular and extracellular anti-cell-death actions rather than a single receptor event.
• Amyloid-associated pathomechanisms — the same review reports antagonism of several Alzheimer-associated pathomechanisms, amyloid plaque accumulation among them.
• Oxidative-stress and apoptosis pathways in ovary and testis — a review reports modulation of several signalling pathways in gonadal tissue, chiefly when the body is in an abnormal state.
• Mitochondrial function under senescence — as a peptide encoded by mitochondrial DNA it is described as cytoprotective, preserving mitochondrial function and cell viability in stressed and senescent cells.

What the studies report

Each item below summarises the paper it is numbered to, written from that paper's own abstract. The badge says how the evidence was produced.

1. 1.
   reviewBiochim Biophys Acta Gen Subj (2022)

   A review of the comparatively thin reproductive literature. In ovary and testis the peptide is reported to regulate the cellular response to oxidative stress and apoptosis through several signalling pathways, chiefly when the body is in an abnormal state. The authors themselves note that relatively few studies have addressed reproduction, that the detailed mechanism needs urgent exploration, and that the applications they raise — male and female infertility, male contraception, glucose metabolism in polycystic ovary syndrome — are proposed directions for further study rather than results.

2. 2.
   reviewBiology (Basel) (2023)

   A systematic review of the link between cellular senescence, this peptide, aging and disease. It presents the peptide as encoded by mitochondrial DNA and cytoprotective — preserving mitochondrial function and cell viability under stress and senescence — and discusses cardiovascular disease, neurodegeneration and cancer as the contexts of interest. The abstract is internally inconsistent: the same passage also describes the peptide as promoting the death of damaged or malfunctioning cells and contributing to inflammation. The authors state that neither senescence nor the peptide's mechanisms have been fully clarified and call for further research.

3. 3.
   reviewBiochim Biophys Acta Gen Subj (2022)

   A narrative review written by the group that discovered the peptide, retracing the identification of the gene in the brain of an Alzheimer's disease patient — where it was found as an antagonising factor against neuronal cell death induced by disease-associated insults — and summarising what has accumulated since. It reports multiple intracellular and extracellular anti-cell-death actions and antagonism of Alzheimer-associated pathomechanisms including amyloid plaque accumulation. It contains no new experiments, and the authors present it as a perspective on a field they themselves call new.

4. 4.
   reviewGrowth Horm IGF Res (2016)

   A review of the functional interface with IGF-I. It records that the authors' own laboratory found the peptide binds IGFBP-3, that later work found it decreases circulating IGF-I, and that IGF-I appears to regulate peptide levels in return. Neuroprotection is named as the original observation, with stroke, cardiovascular and cancer models added since. The review states directly that the exact mechanism by which the peptide and IGF-I regulate each other still needs to be elucidated.

Used in research on