SHLP-2 (Small Humanin-Like Peptide 2)
SHLP-2 is a 12-aa mitochondrial-derived peptide (MDP) encoded in the 12S rRNA mitochondrial gene. More potent than humanin, it reduces oxidative stress, inhibits beta-amyloid-induced apoptosis, and promotes cell survival. Plasma levels decline with age.
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Compound Profile
SHLP-2 (Small Humanin-Like Peptide 2)
Key Data
Research reference only
Research Focus
Preclinical data
⚠ Research & Educational Use Only. SHLP-2 (Small Humanin-Like Peptide 2) is a research chemical documented here for scientific education. All information references peer-reviewed literature and preclinical/clinical study data. Not for human consumption. Not medical advice. Consult a licensed researcher or healthcare professional before any laboratory use.
- More potent than humanin in blocking beta-amyloid-induced apoptosis in neuronal cell lines
- Reduces mitochondrial reactive oxygen species (ROS) and oxidative stress markers
- Promotes cell survival under metabolic stress conditions (glucose deprivation, oxidative insult)
- SHLP-2 (Small Humanin-Like Peptide 2) is not FDA-approved for human use. It is a research chemical for scientific study only.
Research At a Glance
- More potent than humanin in blocking beta-amyloid-induced apoptosis in neuronal cell lines
- Reduces mitochondrial reactive oxygen species (ROS) and oxidative stress markers
- Promotes cell survival under metabolic stress conditions (glucose deprivation, oxidative insult)
- Decreases lipogenesis and fat deposition in adipocytes — favorable metabolic effects
In Plain English
Simple summarySHLP-2 (Small Humanin-Like Peptide 2) is one of six small mitochondria-derived peptides discovered in 2016 by Changhan David Lee's lab at USC -- the same lab that discovered humanin and MOTS-c. These six peptides (SHLP1-6) are encoded in the 16S rRNA region of the mitochondrial genome, like humanin. SHLP-2 is the most biologically active of the six in the initial research: it activates the gp130/JAK/STAT pathway (the same pathway as humanin), reduces reactive oxygen species, promotes mitochondrial biogenesis, and showed protective effects against prostate cancer cell growth and diabetic complications in cell models. Circulating SHLP-2 levels in human blood decline with age, paralleling the pattern seen with humanin.
- More potent than humanin in blocking beta-amyloid-induced apoptosis in neuronal cell lines
- Reduces mitochondrial reactive oxygen species (ROS) and oxidative stress markers
- Promotes cell survival under metabolic stress conditions
The full scientific detail, mechanisms, citations, and dosing data, follows below.
What is SHLP-2 (Small Humanin-Like Peptide 2)?
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SHLP-2 (Small Humanin-Like Peptide 2) is a 12-amino acid mitochondria-derived peptide (MDP) encoded within the 12S ribosomal RNA (mt-RNR1) gene of the mitochondrial genome. It is part of the growing family of mitochondrial-derived peptides — small bioactive peptides encoded within the mitochondrial genome in regions previously thought to be non-coding.
The MDP family was pioneered by Pinchas Cohen's laboratory at the USC Leonard Davis School of Gerontology. Humanin (HN) was the founding member, discovered in 2001 as a 21-amino acid peptide neuroprotective against Alzheimer's-related neuronal death. SHLP-1 through SHLP-6 were subsequently identified from the same mt-12S rRNA region.
**SHLP-2 vs Humanin:** Both are encoded within the same 12S rRNA mitochondrial locus and have similar but distinct sequences. In direct comparison studies, SHLP-2 demonstrated 3-10x greater potency than humanin in blocking beta-amyloid peptide (Aβ25-35 and Aβ1-42)-induced neuronal apoptosis in SH-SY5Y and primary cortical neuron cultures. The greater potency of SHLP-2 at lower concentrations makes it a more interesting research tool.
**Mechanisms of action:** - **Mitochondrial ROS reduction**: Reduces superoxide generation in the mitochondrial electron transport chain; protects against Complex I dysfunction - **Anti-apoptotic**: Inhibits cytochrome c release and caspase-3 activation in response to amyloid and other apoptotic stimuli - **Metabolic effects**: SHLP-2 reduces de novo lipogenesis in adipocytes (downregulates FASN, ACC1) — potentially beneficial for obesity and metabolic syndrome - **Signaling**: Proposed to interact with formyl peptide receptor-like 1 (FPRL1) similar to humanin, activating STAT3 and PI3K/Akt pro-survival pathways
**Aging biomarker:** A cross-sectional study of 134 men from the Baltimore Longitudinal Study of Aging (Cobb et al., 2016) found that circulating SHLP-2 levels inversely correlated with chronological age and positively correlated with various health and vitality measures. Diabetes, cardiovascular disease, and frailty were associated with lower circulating SHLP-2, suggesting it as a potential longevity biomarker.
By the Numbers
Key Research Benefits
Documented effects observed in preclinical and clinical studies on SHLP-2 (Small Humanin-Like Peptide 2). See all Immune System peptides for comparison.
Side Effects & Risks
Adverse effects reported in the research literature. All data sourced from preclinical and clinical study reports. View all peptides' side effects →
Dosing Data from the Literature
Doses referenced below are sourced from published preclinical and clinical studies. Use the peptide dose calculator to convert these values to injection volume.
SHLP-2 is primarily used as a research tool in mitochondrial biology and aging studies:
In vitro studies: 0.1-100 nM for neuroprotection and metabolic assays In vivo (rodent): 50-200 mcg/kg SC or IP for metabolic and aging studies Human circulating levels: Measured in plasma aging studies — levels decline with chronological age
Active areas: Alzheimer's research (amyloid toxicity protection), metabolic aging, mitochondrial function assessment
Administration in Research Settings
Standard reconstitution and administration methodology for laboratory research use.
SC or IP injection in research settings. In vitro addition to cell culture media for neuroprotection and mitochondrial studies.
What the research doesn't show
SHLP-2 is genuinely new science -- the 2016 discovery paper is the primary reference. Most research is in cell cultures and mouse models. The aging-related decline in circulating SHLP-2 is documented in humans, but whether supplementing it back produces meaningful benefits in aging humans is not established. This is a research area worth following but very far from clinical application.
Medical Expert Videos
Physicians, researchers, and pharmacologists explain SHLP-2 (Small Humanin-Like Peptide 2), covering mechanisms of action, clinical context, and study findings.
Videos sourced from YouTube search. KnowYourPeptide does not endorse any individual creator. For research education only.
The Bottom Line
SHLP-2 (Small Humanin-Like Peptide 2) has a growing body of preclinical evidence and a well-characterised safety profile in research settings. The most-studied application is: more potent than humanin in blocking beta-amyloid-induced apoptosis in neuronal cell lines.
The most commonly reported side effect in research subjects is minimal adverse effects observed in preclinical studies at physiological doses. It is a research chemical, not approved for human use.
Frequently Asked Questions
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Quick Reference
How It Compares
Humanin is the best-characterized mitochondria-derived peptide from the 16S rRNA region -- SHLP-2 was discovered later and has a smaller research base. MOTS-c is the 12S rRNA-derived mitochondrial peptide with metabolic/AMPK effects. SHLP-6 has shown anti-obesity properties in preliminary research. The entire SHLP family is very new science and the individual peptides' distinct functions are still being worked out.
Compare SHLP-2 (Small Humanin-Like Peptide 2) side-by-sideResearch Use Only
This information is for educational research purposes only. This is not medical advice. Consult a qualified healthcare professional.