SHLP-6
Research OnlyA 22-amino acid mitochondria-derived peptide with the unique property of being pro-apoptotic—the opposite of its sister peptides humanin and SHLP-2. Discovered in 2016, SHLP-6 may have applications in cancer and senescent cell clearance. Research is very early-stage with minimal published data.
Small Humanin-Like Peptide 6 · SHLP6 · Mitochondrial-Derived Peptide 6
Preclinical evidence only
- Preclinical
- 100%
- Clinical
- 0%
Based on 12 cited sources
Historical editorial rating. No completed numerical assessment is established by this record. These scores are not formal GRADE assessments, measured treatment effects, or safety ratings.
- Recorded primary indication:
- Senolytic / pro-apoptotic cell clearance (theoretical)
- Compound / formulation, population, comparator, outcome and timepoint for the numeric assessment:
- Not recorded in this score record
Community usage signal; not evidence of efficacy or safety. Provenance is not established by this score.
Effectiveness is not established by the available evidence. This is not a safety assessment or recommendation.
Research Depth 9: for SHLP-6 specifically the only cited evidence is the Cobb 2016 discovery paper (PMID 27070352), which is in-vitro cell data and actually characterized SHLP-2/SHLP-3 in depth rather than SHLP-6 (1A in-vitro only =3; 1B high-RoB =2; 1C human N=0 →0; 1D indirect cell surrogates =2; 1E single weak preclinical characterization =2). Mechanism 11: dossier states no binding partner/receptor identified and the pro-apoptotic mechanism is "observed but not explained" (2A target unknown =0; 2B caspase/cytochrome-c pathway hand-wavy =5; 2C no dose-response =2; 2D in-vitro only =4). Plausibility 35: cancer + senolytic claims are large speculative leaps with no demonstrated selectivity (3A =8), pro-apoptotic effect is broadly coherent with mitochondrial apoptosis biology but unconfirmed for the specific claims (3B neutral =13), same-family peptides (humanin/SHLP-2) show the OPPOSITE cytoprotective effect so class analogy is mixed (3C =7), and the claim spans multiple systems without proven specificity (3D =7). Global Coverage 14: only one primary research group, one US lab, <5 SHLP-6-specific studies, no governance review (4A =4, 4B =5, 4C =5, 4D =0). Community Experience 29: niche enthusiast discussion only, short real-world track record, empty positive/negative report arrays, no adverse signal over negligible exposure (5A =8, 5B =8, 5C =6, 5D =7). Effectiveness not established: no quantified human efficacy estimate and no meaningful community effect signal (empty anecdotal reports).
The proposed mechanisms of SHLP-6 are based on limited in vitro studies. The pro-apoptotic activity is observed but the molecular mechanism remains unknown.
How It Works (Simplified)
SHLP-6 is unique among mitochondria-derived peptides for promoting cell death rather than protecting cells:
Unlike humanin and other SHLPs that protect cells, SHLP-6 promotes programmed cell death through unknown mechanisms.
Increased apoptosis (DNA fragmentation) in cultured cells. The specific death pathway (e.g. caspase cascade) was not characterized in the source study.
May counteract humanin’s BAX inhibition and promote cytochrome c release, triggering mitochondrial apoptosis pathway.
Encoded within the mitochondrial 16S rRNA region, like humanin and the other SHLPs. How its mitochondrial origin links to its pro-apoptotic effect is not established.
Key Research: Cobb LJ et al. (2016) discovered SHLP family and identified SHLP-6’s unique pro-apoptotic property. PMID:27070352
Important Limitations
- Mechanism is observed but not explained at the molecular level
- No binding partners or receptors have been identified
- No selectivity for unwanted cells (cancer, senescent) demonstrated
- Only one primary research group has published on SHLP-6
- In vivo effects and safety completely uncharacterized
- Translation to human physiology is entirely speculative
In the single in vitro study, SHLP-6 increased apoptosis (DNA fragmentation) and decreased cell viability in cultured cells over a 24-72h assay window. No in vivo or human timeline data available.
PMID:27070352No dedicated short-term studies exist. Effects beyond the initial apoptosis assay are uncharacterized, and in vivo pharmacokinetics are completely unknown.
No long-term studies exist for SHLP-6. Duration of effect, accumulation, and chronic exposure outcomes are entirely uncharacterized. This represents a critical knowledge gap.
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.
Mots-C
CompatibleMOTS-c focuses on metabolic regulation and exercise mimetic effects, different from SHLP-6's pro-apoptotic mechanism. No known interactions but both are mitochondria-derived peptides.
Foxo4-Dri
CompatibleBoth have potential senolytic applications through different mechanisms. FOXO4-DRI disrupts p53-FOXO4 interaction while SHLP-6's pro-apoptotic mechanism is unknown. Theoretical synergy for senescent cell clearance.
Humanin
AvoidSHLP-6 has opposite effects to humanin—pro-apoptotic vs anti-apoptotic. May counteract humanin's cytoprotective mechanisms. Could theoretically be used to balance humanin's effects in specific contexts.
Shlp-2
AvoidSHLP-2 is cytoprotective like humanin, while SHLP-6 promotes apoptosis. These sister peptides have opposing biological effects despite similar mitochondrial origin.
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.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
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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Compared With
4 comparisonsConditions Studied
2 entries- SHLP-6 for Senescent Cell Accumulation SHLP-6's pro-apoptotic properties suggest theoretical senolytic potential. Senescent cells resist normal apoptosis, and SHLP-6's a…
- SHLP-6 for Cancer Research The pro-apoptotic nature of SHLP-6 makes it conceptually interesting for cancer applications where inducing tumor cell death is de…