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PeptideAI
In vitro onlylongevityimmune

SHLP-6

The shortest of the humanin-like family at 20 residues and the odd one out — it promotes apoptosis rather than blocking it, which makes it a tumour-suppression candidate instead of a cytoprotectant.

Also known as Small humanin-like peptide 6, SHLP6

In vitro only — Cell or tissue studies. A mechanism, not yet an effect in a living body.

Characterised in cell culture and in evolutionary genetics work. There is no animal efficacy programme, no human trial and no dosing precedent. It belongs on this list for completeness of the mitochondrial-derived peptide family, not as something anyone should be taking.

How it works

SHLP-6 comes from the same mitochondrial 16S rRNA region as humanin and the other SHLPs, but its biology runs the opposite way: rather than protecting cells from apoptotic death it promotes it, and in the original Cobb characterisation it reduced viability in cancer cell lines. That has made it a subject of tumour-suppression interest rather than a longevity supplement in the usual sense. A 2023 analysis found evidence of natural selection acting on the SHLP-6 coding region alongside humanin, suggesting these peptides are under real evolutionary constraint and not incidental translation products. Human data are limited to sequence and association work; nothing has been administered to a person.

Targets: Intrinsic apoptosis pathway, Tumour cell viability, Mitochondrial stress signalling

Dosing

ProtocolDoseFrequencyRoute
Research use only — no human protocol existsn/a—not establishedsubcutaneous
  • · No dosing has been established in any species for therapeutic use. SHLP-6 is a laboratory reagent; it does not have a self-administration protocol, and anything presented as one is fabricated.

Cycling

None exists. This compound has no human use pattern to describe.

Work out your exact syringe units →

Pharmacology

Half-life
Not established in any species.
Onset
Unknown.
Routes
subcutaneous
Molecule
Mitochondrial-derived peptide (20 residues)
Sequence length
20 amino acids

Handling

Diluent
Bacteriostatic water
Typical mix
1 or 2 mL
Lyophilised
Freezer.
Reconstituted
Refrigerated and used quickly; no stability data published.
Light sensitive
Yes — keep it out of the light

Mixing

Supplied in research quantities only.

Side effects

  • commonUnknown — no human exposure data— A systemically pro-apoptotic peptide with no safety characterisation is a meaningfully different risk proposition from the rest of this class.

Do not use if

  • Essentially all non-research human use — there is no established safe dose, and the mechanism is cell death rather than cell protection.
  • Pregnancy and breastfeeding — no data.

Combining it

  • conflictshlp-2 — Directly opposing effects on apoptosis within the same peptide family.
  • conflicthumanin — Humanin blocks BAX-mediated apoptosis; SHLP-6 promotes apoptosis.

What to monitor

  • · Nothing established.

Legal status

Not approved anywhere; a research reagent.

References

  • Cobb et al. 2016, Aging — characterisation of the SHLP family of mitochondrial-derived peptides (preclinical)
  • Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6, Scientific Reports 2023 (other)

Mechanism in depth

SHLP-6 is the family's outlier and the reason it is worth understanding is that it inverts the assumption people bring to this class. Humanin, SHLP-2 and SHLP-3 are cytoprotective — they hold the intrinsic apoptosis pathway shut. SHLP-6 does the opposite: in the original Cobb characterisation it promoted apoptosis and reduced viability in cancer cell lines, which is why it has been discussed as a tumour-suppression candidate rather than as a longevity supplement. The upstream molecular mechanism is not established. Nobody has identified what SHLP-6 binds, what receptor if any it engages, or why it should push the intrinsic pathway open when its near neighbours push it shut. The 2023 Scientific Reports analysis by Gruschus and colleagues found evidence of natural selection acting on both the humanin and SHLP6 coding regions, which is a genuinely useful piece of evidence: it argues these open reading frames are under real evolutionary constraint and are not incidental translation noise from a ribosomal RNA gene, which was a legitimate objection to the whole field. That is an argument for the peptide being biologically real. It is not an argument for anyone taking it. There is no animal efficacy programme, no dosing work, and nothing has been administered to a person.

What usually goes wrong

The category error. SHLP-6 appears on longevity lists because it shares a name and a genomic address with humanin, and people assume it belongs to the same therapeutic family. It does the opposite thing. A systemically administered pro-apoptotic peptide with no dose-finding work, no animal safety programme and no human exposure data is a materially different risk proposition from the cytoprotective members of the family, and it should not be reasoned about as though it were another anti-ageing peptide. There is no established safe dose, there is no protocol, and any protocol presented as one has been fabricated. This is a laboratory reagent.

Pharmacokinetics

Metabolism
Presumed proteolytic. Uncharacterised.
Elimination
Unknown.

Receptor targets

  • Intrinsic apoptosis pathway — No binding partner identified.

    Promotes apoptosis — the functional mirror image of humanin and SHLP-2. The molecular node at which it acts is unknown.

  • Tumour cell viability — Not applicable.

    Reduced viability in cancer cell lines in the original characterisation, which is the basis for tumour-suppression interest.

What to expect, and when

Unknown. Nothing has been administered to any animal on a therapeutic schedule, let alone a person, so there is no time course to describe.

Stacking and comparisons

There is no stacking guidance because there is no use pattern. What is worth stating is the internal contradiction: SHLP-6 is pro-apoptotic and humanin and SHLP-2 are anti-apoptotic, and they are all encoded in the same short stretch of mitochondrial DNA. If a vendor sells you a 'mitochondrial-derived peptide blend' containing several SHLPs, the components are pharmacologically opposed and the blend has no coherent net direction. That is not a subtle point — it is the single most useful thing to know about this peptide when you encounter it on a product page.

Against every other compound on this page: SHLP-6 is the one that is not a longevity intervention at all. It is included for completeness of the mitochondrial-derived peptide family and because people encounter the name in that context and assume it belongs alongside humanin. Its closest conceptual neighbours are not the other SHLPs but the senolytics — a compound whose therapeutic idea is making cells die. Unlike FOXO4-DRI, which at least has selectivity logic and a landmark animal study behind it, SHLP-6 has neither.

Rough cost

Not estimable. SHLP-6 is a research reagent sold at reagent pricing in research quantities, and there is no protocol against which to compute a monthly cost.

Genuinely uncertain

  • No pharmacokinetic data of any kind exist in any species.
  • No molecular binding partner or receptor has been identified.
  • The mechanism by which it promotes apoptosis, in contrast to its near-identical-origin siblings, is entirely unexplained.
  • There is no animal efficacy or safety programme.
  • Molecular weight is not stated in the Core record and no published value was resolved.
  • Whether circulating SHLP-6 changes with age — as documented for humanin and SHLP-2 — was not established in what I could access.
  • No stability, storage or handling data are published.

Papers