SS-31 vs Humanin

Humanin is a natural 24-amino-acid peptide encoded in mitochondrial DNA and studied as a cytoprotective factor. SS-31 is a synthetic tetrapeptide designed to stabilise mitochondrial membranes.

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SS-31

A mitochondria-targeted tetrapeptide that binds cardiolipin in the inner mitochondrial membrane — approved in the US in 2025 for Barth syndrome.

BEST STUDIED FOR

Mitochondrial & longevity

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	SS-31	Humanin
The key difference	Synthetic membrane-targeting peptide	Native mitochondrial-derived peptide
Class	Mitochondrial & longevity	Mitochondrial & longevity
Mechanism	SS-31 concentrates in the inner mitochondrial membrane and binds cardiolipin, the lipid that holds the electron-transport chain together.	Humanin was discovered protecting neurons from Alzheimer’s-related insults.
Status	Accelerated US approval (September 2025) to improve muscle strength in Barth syndrome; further trials in other mitochondrial disorders.	Preclinical and observational research; the S14G analogue (HNG) is a more potent research form. No approved medicine.
Reported safety signals	Clinical programmes report injection-site reactions as the most common effect.	No human interventional safety data.
A key study	Summarises the September 2025 US accelerated approval of elamipretide for muscle strength in Barth syndrome. (Drugs 2026, PMID 41335372)	Reviews humanin as a 24-residue factor that suppresses neuronal death from Alzheimer’s-related insults. (Mol Neurobiol 2004, PMID 15655255)

SS-31 for mitochondrial-membrane pharmacology; humanin for endogenous signalling research. Both are discussed here strictly as research compounds; nothing on this page is medical advice or a dosing guide.

REFERENCES (PUBMED)

[SS-31] Elamipretide: First Approval — Drugs 2026. PMID 41335372
[SS-31] Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential — Int J Mol Sci 2025. PMID 39940712
[SS-31] The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin — J Am Soc Nephrol 2013. PMID 23813215
[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

FREQUENTLY ASKED

What is the difference between SS-31 and Humanin?

Humanin is a natural 24-amino-acid peptide encoded in mitochondrial DNA and studied as a cytoprotective factor. SS-31 is a synthetic tetrapeptide designed to stabilise mitochondrial membranes.

What is the regulatory status of SS-31 and Humanin?

SS-31: Accelerated US approval (September 2025) to improve muscle strength in Barth syndrome; further trials in other mitochondrial disorders. Humanin: Preclinical and observational research; the S14G analogue (HNG) is a more potent research form. No approved medicine.

What safety signals have been reported?

SS-31: Clinical programmes report injection-site reactions as the most common effect. Humanin: No human interventional safety data.

Which studies is this comparison based on?

For SS-31: “Elamipretide: First Approval” (PMID 41335372); “Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential” (PMID 39940712); “The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin” (PMID 23813215). 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).