Humanin vs SHLP2

SHLP2 belongs to a family of six small humanin-like peptides found in the same mitochondrial gene region as humanin, with overlapping cytoprotective effects in cell models.

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Humanin

A 24-amino-acid peptide encoded in the mitochondrial genome — the first mitochondrial-derived peptide described — studied for cytoprotection.

BEST STUDIED FOR

Mitochondrial & longevity

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SHLP2

A mitochondrial-derived peptide encoded in the 16S rRNA region, studied as an insulin sensitiser and cytoprotective signal.

BEST STUDIED FOR

Mitochondrial & longevity

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SIDE BY SIDE

	Humanin	SHLP2
The key difference	First-described mitochondrial-derived peptide	Small humanin-like peptide 2
Class	Mitochondrial & longevity	Mitochondrial & longevity
Mechanism	Humanin was discovered protecting neurons from Alzheimer’s-related insults.	SHLP2 belongs to the humanin-like peptide family.
Status	Preclinical and observational research; the S14G analogue (HNG) is a more potent research form. No approved medicine.	Preclinical and observational human biomarker studies only.
Reported safety signals	No human interventional safety data.	No human interventional safety data.
A key study	Reviews humanin as a 24-residue factor that suppresses neuronal death from Alzheimer’s-related insults. (Mol Neurobiol 2004, PMID 15655255)	In mice, systemic and central SHLP2 protected against diet-induced obesity and improved insulin sensitivity via POMC neurons. (Nat Commun 2023, PMID 37468558)

WHEN TO RESEARCH WHICH

Humanin is the reference; SHLP2 a newer family member. Both are discussed here strictly as research compounds; nothing on this page is medical advice or a dosing guide.

REFERENCES (PUBMED)

[Humanin] Humanin: after the discovery — Mol Neurobiol 2004. PMID 15655255
[Humanin] Humanin: Functional Interfaces with IGF-I — Growth Horm IGF Res 2016. PMID 27082450
[Humanin] Humanin and Its Pathophysiological Roles in Aging: A Systematic Review — Biology (Basel) 2023. PMID 37106758
[SHLP2] Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons — Nat Commun 2023. PMID 37468558
[SHLP2] Mitochondrial-derived peptides in energy metabolism — Am J Physiol Endocrinol Metab 2020. PMID 32776825
[SHLP2] Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration — Sci Rep 2018. PMID 30310092

FREQUENTLY ASKED

What is the difference between Humanin and SHLP2?

SHLP2 belongs to a family of six small humanin-like peptides found in the same mitochondrial gene region as humanin, with overlapping cytoprotective effects in cell models.

What is the regulatory status of Humanin and SHLP2?

Humanin: Preclinical and observational research; the S14G analogue (HNG) is a more potent research form. No approved medicine. SHLP2: Preclinical and observational human biomarker studies only.

What safety signals have been reported?

Humanin: No human interventional safety data. SHLP2: No human interventional safety data.

Which studies is this comparison based on?

For Humanin: “Humanin: after the discovery” (PMID 15655255); “Humanin: Functional Interfaces with IGF-I” (PMID 27082450); “Humanin and Its Pathophysiological Roles in Aging: A Systematic Review” (PMID 37106758). For SHLP2: “Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons” (PMID 37468558); “Mitochondrial-derived peptides in energy metabolism” (PMID 32776825); “Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration” (PMID 30310092).