SHLP-2
Research OnlyAlso known as: Small Humanin-Like Peptide 2, SHLP2, Mitochondrial-Derived Peptide 2
A 26-amino acid mitochondria-derived peptide (MDP) discovered in 2016 from the same mitochondrial DNA region as humanin. Shows cytoprotective, metabolic, and potential longevity effects in preclinical studies. Part of an emerging class of mitochondrial signaling molecules, but human therapeutic data is lacking.
Research Statistics
Emerging mitochondrial-derived peptide; primarily US and limited international preclinical research. Mechanism as mitochondria-derived cytoprotective signal is plausible but early-stage without human trial data.
Research Dossier
Overview
What is SHLP-2 and what does the research say?
Mechanism of Action
The proposed mechanisms of SHLP-2 are based primarily on animal and in vitro studies. Human therapeutic data is lacking, though observational studies have identified protective genetic variants.
How It Works (Simplified)
SHLP-2 appears to act as a mitochondrial signaling molecule through several pathways:
Binds to chemokine receptor CXCR7, activating MAPK-ERK1/2 signaling cascade that regulates hypothalamic POMC neurons controlling appetite and thermogenesis.
Directly binds to mitochondrial complex 1, stabilizing this critical enzyme and protecting against dysfunction linked to neurodegeneration.
Exhibits chaperone-like properties, binding to misfolded protein seeds and preventing amyloid aggregation associated with metabolic and neurodegenerative diseases.
Activates anti-apoptotic pathways by reducing BAX/p53 and increasing BCL-2, while enhancing mitochondrial biogenesis through PGC-1a upregulation.
Scientific Pathways
CXCR7-MAPK Pathway (Energy Homeostasis)
SHLP-2 → CXCR7 binding → MAPK-ERK1/2 phosphorylation → POMC neuron activation
↓
Appetite suppression + ThermogenesisMitochondrial Protection (Neuroprotection)
SHLP-2 → Complex 1 binding → Enzyme stabilization → Preserved mitochondrial functionKey Research: Kim SJ et al. (Nature Communications, 2023) identified CXCR7 as the receptor for SHLP-2 and demonstrated its role in hypothalamic energy regulation. PMID:37468558
Important Limitations
- Research is recent (discovery in 2016) with limited independent replication
- Most studies from a single research group (USC Cohen lab)
- No human therapeutic administration studies exist
- Translation from animal models to human physiology is unconfirmed
- Pharmacokinetics and bioavailability in humans not characterized
Evidence-Chained Benefits
Evidence-Chained Benefits
Research findings linked to mechanisms and clinical outcomes
What to Expect
Timeline based on observations from published studies. Individual responses may vary.
Based on preclinical observations: Initial receptor binding and signaling cascade activation may begin. Animal studies show metabolic parameter changes within days of administration. No human timeline data available.
Animal studies suggest ongoing metabolic and mitochondrial effects. Mouse models showed improved insulin sensitivity and reduced weight gain during this period. Cytoprotective signaling likely established.
Preclinical models show sustained metabolic improvements. Studies demonstrate continued mitochondrial biogenesis enhancement and maintained cytoprotective effects over several weeks of treatment.
Long-term animal studies suggest persistent effects on mitochondrial function and metabolism. However, human pharmacokinetics, duration of effect, and optimal treatment length are completely unknown.
Research-Based Observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Quality Checklist
Visual indicators to help evaluate SHLP-2 product quality
Good Signs (6 indicators)
Warning Signs (5 indicators)
Bad Signs (6 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
Peptide Interactions
Known and theoretical interactions when combining SHLP-2 with other peptides. Based on published research and mechanistic considerations.
Humanin
SynergisticBoth are mitochondria-derived peptides from overlapping mtDNA regions. SHLP-2 and humanin share cytoprotective mechanisms but act through distinct receptors. Complementary protective effects likely without antagonism.
Mots-C
CompatibleDifferent mitochondria-derived peptide with metabolic effects. MOTS-C primarily affects AMPK pathway while SHLP-2 acts via CXCR7. Non-overlapping mechanisms suggest compatibility.
Shlp-6
CompatibleSame peptide family but different effects. SHLP-6 shows pro-apoptotic properties while SHLP-2 is anti-apoptotic. May have balancing effects in cellular stress response.
Ss-31
CompatibleBoth target mitochondria but through different mechanisms. SS-31 stabilizes cardiolipin while SHLP-2 binds complex 1. Potentially complementary mitochondrial support.
BPC-157
CompatibleNon-overlapping mechanisms. BPC-157 focuses on tissue repair while SHLP-2 provides mitochondrial protection. No known interactions or contraindications.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
References
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
Methodology Note
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
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