STUDresearch · Peptide
SHLPs (small humanin-like peptides)
Also known as
SHLP1–6 · SHLP1 · SHLP2 · SHLP3 · SHLP4 · SHLP5 · SHLP6 · small humanin-like peptides · small humanin-like peptide 2 · mitochondrial-derived peptides SHLP · MT-RNR2 SHLPs · 16S rRNA SHLPs · K4R-SHLP2 · K4R SHLP2 · m.2158T>C SHLP2 variant
Community talk. May be wrong. Not medical advice. Not a protocol. Not for human or animal use.
Peptide
Niche talk
Systemic
SubQ / animal IP–ICV
Mitochondrial & metabolic peptides
Systemic class — circulating mitochondrial-derived signals encoded in mtDNA 16S rRNA (MT-RNR2), same genomic neighborhood as humanin.
What people say
SHLP1–6 are distinct mitochondrial-derived peptides encoded within MT-RNR2. SHLP2 and SHLP3 were cytoprotective in founding assays, while SHLP6 showed different pro-apoptotic behavior.
Doses people talk about
The first row preserves unverified SHLP6 retail history, not a recommendation. The remaining rows are animal designs, not human translations; isoform, sequence, species and route matter.
How it may feel
Legacy notes mention little acute effect, subtle energy or recovery, and vague well-being over weeks. These remain unverified reports; the inspected forum thread did not supply a quantified standalone course.
Legacy SHLP6 retail chart50–150 mcg SC every other day or 3×/week
Inherited ~2 mg vial and morning-stack lore, not human dose-ranging; SHLP6 and SHLP2/3 had opposing apoptotic behavior in founding assays.
SHLP2 male-mouse metabolic study2 mg/kg IP once daily for about 3 weeks
Systemic male-mouse high-fat-diet design; it does not establish human SC dosing or a community schedule.
SHLP2 central animal studies3 µg ICV; separate continuous 0.16 µg/kg/min rat infusion
Laboratory-only central administration in acute assessments and clamp work; not a self-administration route.
Half-life & effect duration
- Half-life in the body
- SHLP1–6No single settled estimate
- Felt duration people report
- Existing community reportsDay-1 sensations or no effect; subtle energy or recovery around weeks 1–2
- Longer claimsWell-being changes around weeks 4–8
Cycles people discuss
Four-to-twelve-week blocks are vendor or borrowed mitochondrial-peptide culture, not an empirical SHLP human calendar. Published interventions are short cell or animal designs.
Timing
Morning SubQ appears in legacy vendor timing notes as stack logistics, not PK-based scheduling; the proposed SHLP2/SHLP6 pairing remains biologically contested.
Stacks
Humanin, MOTS-c and SS-31 appear in mitochondrial-peptide stacks, but there is no validated combination protocol and combining different SHLP isoforms can obscure their opposing cell-assay profiles.
Watch for
Human safety gap: No solid human adverse-event database, interaction table, pregnancy data, or long-term dose-ranging for exogenous SHLP1–6. Silence is not proof of safety.
Tap a line to jump into the full notes. Research only — may be wrong.
Timing context & sources
Half-life in the body
No dependable human half-life or bioavailability was established for SHLP1–6.
The literature documents cell assays, endogenous human associations and rodent interventions. K4R-SHLP2 was more stable than wild type in experimental systems, but that is not a human elimination value.
Different isoforms and sequences, preclinical routes and no exogenous human PK study; a dosing interval cannot be inferred from animal schedules.
- Cobb et al. (2016): naturally occurring small humanin-like peptides (opens in a new tab)Abstract, figures and methods context reviewed: discovery of SHLP1–6; distinct viability/apoptosis effects; SHLP2/3 mitochondrial and insulin-sensitivity experiments; cell assays and animal infusion designs.Foundational preclinical study, not a human administration, safety, dose-ranging or pharmacokinetic trial.
- Kim et al. (2024): naturally occurring K4R-SHLP2 variant in Parkinson's disease (opens in a new tab)Abstract and figure descriptions reviewed: K4R-SHLP2 showed greater experimental stability than wild type, complex-I binding, cell protection and protection in an MPTP mouse model.Genetic association plus cell and mouse model; not a human exogenous-treatment PK or dose-comparison study.
- Kim et al. (2023): SHLP2 regulates energy homeostasis through hypothalamic neurons (opens in a new tab)Abstract and indexed figures/methods reviewed: systemic and ICV SHLP2 in male high-fat-diet mice, insulin sensitivity, POMC-neuron and CXCR7 mechanistic findings.Male-mouse intervention and mechanistic work; no human efficacy, safety, SC bioavailability or felt timing.
Felt duration people report
No dependable single-dose human SHLP felt-duration window was established.
Legacy notes retain uncertain day-1/null reports, subtle energy or recovery at weeks 1–2 and vendor or vague well-being timelines at weeks 4–8. The short inspected forum thread asked about SHLP2 without documenting an amount, route and observed course; it neither validates nor disproves the inherited reports.
The inspected community evidence is limited, and the cited interventions are preclinical. An incomplete report does not establish absence of effect, a typical response or safety.
- SHLP2 peptide/new? community thread (opens in a new tab)Complete visible thread reviewed: the opening author asked whether anyone had heard of or taken SHLP2; a later commenter discussed having seen research and not finding a source, without reporting a personal amount, route or outcome course.Very short multi-author thread and no complete first-person intervention report; sourcing text was not copied into the reader summary.
What people say
- Sparse self-experiments: Rare longevity-forum and MDP-stack footnotes mention “mito resilience,” subtle energy, or metabolic steadiness—far thinner logs than MOTS-c or HNG. anecdote
- Cell survival (SHLP2/3): At ~100 nM in serum-free culture, SHLP2 and SHLP3 increased viability and decreased apoptosis in NIT-1 β-cells and 22Rv1 prostate cancer cells. lab
- Proliferation split: SHLP2 and SHLP4 promoted BrdU proliferation in NIT-1 β-cells; not a uniform class effect. lab
- Opposite pole (SHLP6): SHLP6 significantly increased apoptosis in the same NIT-1 / 22Rv1 panels where SHLP2/3 were protective—founding reason community lore says “don’t treat SHLPs as interchangeable.” lab
- Mito energy (SHLP2/3): Raised oxygen consumption rate (OCR) and cellular ATP in 22Rv1 cells after ~100 nM overnight exposure. lab
- ROS dampening: Pre-incubation with SHLP2 or SHLP3 suppressed serum-starvation-driven ROS (DHE) in NIT-1 and 22Rv1 cells. lab
- STS / caspase axis: SHLP2 and SHLP3 blocked staurosporine-induced apoptosis and related mitochondrial membrane / caspase-3 activation in NIT-1 cells. lab
- Signaling: SHLP2 activated ERK and STAT3 phosphorylation with different kinetics than humanin; SHLP3 activated ERK later and did not activate STAT3 in the same NIT-1 readouts—mechanism is not a single shared cascade. lab
- Adipocyte differentiation: With insulin, ~100 nM SHLP2 or SHLP3 for 7 days accelerated 3T3-L1 pre-adipocyte differentiation (Oil Red-O). lab
- Central insulin sensitization (SHLP2, rats): Continuous ICV SHLP2 at ~0.16 μg/kg/min during hyperinsulinemic-euglycemic clamp raised glucose infusion rate ~50%, suppressed hepatic glucose production, and increased peripheral glucose uptake. SHLP3 did not show the same in vivo clamp effect in that design. animal
- Peripheral biomarker pulse (mice): SHLP2 or SHLP3 at 2 mg/kg/dose IP BID for 5 days raised leptin; SHLP3 also raised IL-6 and MCP-1, which authors linked to why SHLP3 lacked the in vivo insulin-sensitizing clamp signal. animal
- Diet-induced obesity / body comp (SHLP2): Daily IP SHLP2 ~2 mg/kg for ~3 weeks in HFD mice protected against weight gain, reduced fat mass and leptin, shrank inguinal/epididymal WAT depots, and reduced hepatic steatosis endpoints in published metabolic work. animal
- Acute food-intake dose finding: IP dose-ranging identified ~2 mg/kg as an effective acute food-intake suppression dose for SHLP2 in the Kim et al. energy-homeostasis study. animal
- ICV energy homeostasis: Third-ventricle SHLP2 ~3 μg protected male mice from HFD obesity phenotypes, increased thermogenic gene / UCP1 signaling in iBAT, and improved glucose tolerance in that model. animal
- Metabolomics (short course): SHLP2 2.5 mg/kg IP twice daily for 3 days in DIO mice altered plasma lipid/amino-acid metabolite profiles (including sphingolipid pathway intermediates). Humanin/HNG was run in parallel in the same design. animal
- Parkinson’s / K4R variant: mtSNP m.2158 T>C produces K4R-SHLP2 (Lys→Arg at position 4), associated with reduced PD risk and greater peptide stability than wild-type; K4R 2.5 mg/kg IP BID protected striatal TH better than WT in MPTP mice; both WT and K4R rescued striatal dopamine vs MPTP alone in reported HPLC data. animal
- Cellular PD toxins: ~2.5 μM WT or K4R SHLP2 in SH-SY5Y + MPP+ and related mito readouts (TFAM/mtDNA, NAD+, complex I binding discussion). lab
- Amyloid-β neurons: SHLP2 (not SHLP3) reduced Aβ1–42 cytotoxicity in primary cortical neurons across ~1 nM–10 μM co-treatment ranges in the Cobb panel. lab
- IAPP chaperone angle: SHLP2 (with HNG) studied for chaperone-like activity against islet amyloid polypeptide misfolding—T2D mechanism interest, not a clinical diabetes therapy. lab
- Circulating decline: Mouse plasma SHLP2 falls with age (young ~3 mo vs old ~18 mo; males higher than females in that ELISA); human serum SHLP2 reported lower in obesity/diabetes cohorts and declines with age in MDP literature; inverse associations discussed with prostate-cancer risk / fat measures in observational work. trial
- AMD RPE cybrids (SHLP2): Exogenous SHLP2 preserved OXPHOS complex subunits, supported mtDNA copy / PGC-1α framing, downregulated effector caspases 3/7, and protected against amyloid-β toxicity in AMD transmitochondrial RPE models. lab
Doses people talk about
- Class sparsity: There is no stable, multi-forum consensus mcg chart for SHLP1–6 comparable to BPC-157 or MOTS-c. Most human-facing numbers are vendor extrapolations or single-site research-peptide tables. forum
- Legacy SHLP6 retail chart: Inherited vendor/community notes list ~50–150 mcg SC every other day or 3×/week from ~2 mg vial products, sometimes morning SubQ alongside SHLP2 in “full MDP protocol” language. This is unverified retail/stack lore, not a human PK, safety or dose-ranging result; SHLP6 and SHLP2/3 showed opposing apoptotic behavior in founding cell assays, making that pairing controversial rather than a biology-aligned default. The inspected forum thread did not supply a complete firsthand course. forumlab
- Schedule culture vs animal daily IP: Community EOD/3× weekly schedules are convenience/analog habit, not matched to the daily (or BID) IP designs that drive most rodent endpoints. forum
- Purity flag: Emerging MDP peptides often lack independent HPLC/identity verification; under-dose, over-dose, and wrong sequence are documented gray-market failure modes across the class. forum
- Isoform caution: Confirm SHLP2 vs SHLP3 vs SHLP6 on the COA/label. A “SHLP blend” without ratios is especially high mislabel risk. forum
- Framing: Preclinical doses and sparse gray-market charts only—not medical advice; no established human therapeutic dose, no FDA-approved SHLP product, no large human PK/PD table. forum
- Cell assay concentrations (context only): ~100 nM SHLP2/3 for viability, OCR, ROS, STS, and differentiation assays; ~2.5 μM in some PD/mito cell systems; Aβ neuron rescue tested from ~1 nM to 10 μM. These do not convert 1:1 into injectable human mcg charts. lab
- Variant caution: Wild-type SHLP2 vs K4R differ in stability and PD-model performance—do not assume equal potency or copy doses across sequences. Most gray-market vials do not specify K4R. trial
- Mouse metabolic IP (SHLP2): ~2 mg/kg IP once daily for ~3 weeks for HFD body-composition / steatosis endpoints (Kim et al., Nat Commun 2023 and related summaries). animal
- Mouse metabolic short course: ~2.5 mg/kg IP twice daily for 3 days for plasma metabolomics in DIO mice (Mehta et al. 2019). animal
- Mouse biomarker pulse: ~2 mg/kg/dose IP BID for 5 days for leptin/cytokine panels (Cobb et al. 2016). animal
- MPTP PD model: ~2.5 mg/kg IP BID SHLP2 (WT or K4R), often with multi-day pretreatment before MPTP; MPTP itself in those designs is a multi-mg/kg neurotoxin regimen—not a human template. animal
- Allometric warning: Multi-mg/kg mouse IP does not safely or simply map to 50–200 mcg human SC charts. Any “mouse-to-human calculator” for SHLPs is speculative. animal
- ICV research only (SHLP2): ~3 μg into the third ventricle for acute/short-window metabolic assessments; continuous ICV ~0.16 μg/kg/min in rat clamp work. Neither is a self-administration route. animal
How it may feel
- Honest baseline: Public self-experiment volume is thin. Most “feel” language is borrowed from humanin/MOTS-c culture or from multi-MDP stacks, not from large standalone SHLP trial logs. forum
- Day 0 / injection: Inherited gray-market discussion describes SC site awareness—sting, warmth or redness—and does not frame a stimulant kick as class-typical. These are general injection expectations, not a documented SHLP first-dose pattern. The originally inspected forum thread asked about SHLP2 but supplied no complete firsthand course. forum
- Days 1–7: Inherited notes describe sparse acute systemic reports and little or no distinct day-1 effect beyond injection logistics. That is uncertain legacy/null-response context, not a prediction that most people will feel nothing. The inspected community material did not establish a same-author first-week course with an amount and route. anecdoteforum
- Weeks 1–2: Inherited anecdotal notes mention occasional subtle energy, “metabolic steadiness” or recovery, described as less dramatic than stimulants or GLP-1s. These unverified reports are retained separately from cell and male-mouse SHLP2 findings; the inspected forum thread does not corroborate a quantified standalone human course. anecdoteforum
- Weeks 3–4: Community caution is to check whether any change is separable from diet, sleep, training, or co-stacked MOTS-c / HNG / NAD agents. forum
- Weeks 4–8: Inherited vendor charts claim that cellular benefits take 4–8 weeks to measure, alongside vague well-being stories and concern that null responses are under-reported. These are retail/legacy expectations, not established human outcomes or a measured frequency of nonresponse. The inspected literature and short forum discussion do not validate that timeline. forum
- Months 2–3: Very thin public logging; more “I’m running the MDP suite” habit than SHLP-specific outcome series. forum
- SHLP6-specific framing: Anyone chasing longevity/cytoprotection who unknowingly runs SHLP6 is on the wrong polarity relative to SHLP2/3 cell data—feel logs cannot fix isoform error. forum
Cycles people discuss
- Vendor/community blocks: ~8–12 week research cycles appear on some SHLP2/SHLP6 product pages, mirroring broader MDP longevity planning. forum
- Shorter exploratory blocks: ~4–8 weeks still appear when people treat SHLPs as footnotes to humanin/MOTS-c seasons. forum
- Off periods: Sparse SHLP-specific guidance; users often borrow humanin/MOTS-c style off blocks (e.g. multi-week off after multi-month on) as precaution given absent long-term human safety databases. forum
- Re-runs: Occasional “mito season” restarts once or a few times per year; no solid long-term safety or tachyphylaxis database. forum
- Animal design lengths: Daily IP ~3 weeks (metabolic body-comp); 5-day BID biomarker pulses; multi-day pretreatment + toxin windows in PD models—none of these define a human on/off calendar. animal
- SHLP6 oncology framing: Any research interest in pro-apoptotic biology is not the same as a longevity cycle and should not be mixed casually into anti-apoptotic MDP stacks. forum
Timing
- Downstream vs plasma: Plasma disappearance ≠ pathway effects gone; mito metabolism, cytoprotection, and hypothalamic-peripheral glucose flux are discussed as durable pathway effects after exposure. anecdote
- Morning SubQ habit: Vendor timing notes often say morning injection—habit and stack logistics, not PK-proven peak matching. forum
- Human PK: No solid published human half-life, bioavailability, or SC vs IV table for SHLP1–6 as of last research pass. trial
- Class assumption: Short circulating duration is assumed for these small peptides—similar lore as humanin (~tens of minutes in mouse HNG PK discussions)—but SHLP-specific plasma t½ numbers are not established like clinical drugs. trial
- Animal schedule context: Daily or BID IP regimens appear in metabolic and Parkinson’s-disease papers. The inherited interpretation is that investigators sought ongoing exposure rather than a monthly depot, but an administration schedule does not measure elimination or establish a human interval. animal
- K4R stability: K4R-SHLP2 reported more stable than wild-type, which is part of the PD-protection mechanistic story—not a community half-life chart. trial
- Tissue detection (mice): SHLP1 heart/kidney/spleen; SHLP2 liver/kidney/muscle; SHLP3 brain/spleen; SHLP4 liver/prostate; SHLP6 liver/kidney (SHLP5 antibody generation failed in the founding paper). animal
More on what it is
- Why people search: Lesser-known siblings of humanin and MOTS-c. Search volume concentrates on SHLP2 (metabolism, aging decline, PD K4R variant, AMD cybrids) and occasionally SHLP6 (pro-apoptotic / oncology angle). forum
- What they are: Six short mitochondrial-derived peptides (SHLP1–6), ~20–38 amino acids, encoded by small open reading frames inside the mitochondrial 16S rRNA gene (MT-RNR2)—the same region that encodes humanin. Lengths commonly listed: SHLP1 24 aa, SHLP2 26 aa, SHLP3 38 aa, SHLP4 26 aa, SHLP5 24 aa, SHLP6 20 aa. trial
- Discovery: Identified in silico then validated (immunoblot, transcript work) in the Pinchas Cohen / USC–UCLA mitochondrial peptide program; foundational functional paper Cobb et al., Aging 2016. trial
- Not one drug: SHLP2 and SHLP3 generally support cell survival, raise OCR/ATP, and reduce ROS in cell models; SHLP6 increases apoptosis in the same founding assays—so isoform identity is a first-order safety and goal question. lab
- Evidence honesty: Almost entirely cell and rodent work, plus human circulating-level associations. No large human RCTs establishing longevity, metabolic, or neuroprotective “use” protocols. trial
- Not the same as: Native humanin, HNG (S14G-humanin), MOTS-c (12S rRNA / MT-RNR1), or SS-31 (synthetic mito-targeting tetrapeptide). Related MDP neighborhood, different sequences and mechanisms. trial
- Conservation note: Across vertebrates, humanin and SHLP6 show stronger conservation / selection signals than SHLP1–3/5 in some analyses—interesting for biology, not a community dosing rule. trial
Stacks
- MDP trio / suite: SHLP2 + humanin (or HNG) + MOTS-c is the longevity-cluster stack people name most—cytoprotection + metabolic reprogramming narrative. Ratios/doses vary; no validated combo protocol. forum
- Mito membrane + signal: SHLP2 (or class) next to SS-31 / elamipretide-class for “membrane repair + MDP signaling.” forum
- NAD-axis: With NMN, NR, or injectable NAD+ in energy/aging stacks—common confounding when people credit SHLP alone. forum
- Prefer isolate SHLP2: Isolation is repeatedly advised so SHLP6’s pro-apoptotic cell profile is not co-administered with SHLP2/3 survival goals. forum
- SHLP2 + SHLP6 “full protocol” charts: A minority of vendor tables suggest running both—biologically contested because founding assays put them on opposite apoptotic poles; treat as marketing, not consensus biology. forum
- Avoid treating “SHLP blend” as optimized: Without stated mg ratios and identity testing, blends are opacity, not synergy. forum
- Vs humanin alone: Users who bounce from MOTS-c sometimes chase SHLP2 for neuroprotective rather than exercise-mimetic goals—thin evidence, real search pattern. forum
- “Fourth pillar” lore: Some research-peptide writeups cast SHLP2 as completing a suite with humanin (anti-apoptosis), MOTS-c (AMPK/metabolic), and SS-31 (membrane cardiolipin/ETC framing). Marketing taxonomy, not a clinical regimen. forum
Storage notes
- No mix instructions here: STUDresearch does not list reconstitution, diluent volumes, or syringe unit charts. People reconstitute many different ways and vial labels differ — that content creates more confusion than clarity. forum
- Storage (general talk only): Unopened research products are usually kept cool, dry, and away from light per the seller label. Anything after first use is product-specific — follow the label, not a universal forum SOP. forum
Watch for
- Injection logistics: Local irritation, redness, itch, and sterile-technique infection risk like other SC research peptides. forum
- Cancer / malignancy-history debate: Survival signaling (SHLP2/3) vs apoptosis induction (SHLP6) fuels theoretical concern on both sides—anti-apoptotic MDPs in people with cancer history, and pro-apoptotic peptides without oncology supervision. Discussion only; no clinical risk table. forum
- Source / identity quality: Mislabel (wrong SHLP number), under-purity, endotoxin, and absent sequence confirmation are practical gray-market risks for an Emerging class. forum
- Stack confound: Effects (or sides) are hard to attribute when stacked with humanin/HNG, MOTS-c, SS-31, and NAD-axis agents. forum
- Low discussion volume: Few documented failure modes means unknown unknowns dominate—Emerging compounds fail closed on safety claims. forum
- Class split risk (highest conceptual caution): SHLP6 is pro-apoptotic in founding cell models while SHLP2/3 are cytoprotective—wrong isoform or unlabeled blend can oppose the intended goal. lab
- Human safety gap: No solid human adverse-event database, interaction table, pregnancy data, or long-term dose-ranging for exogenous SHLP1–6. Silence is not proof of safety. trial
- SHLP3 inflammatory markers: In the 5-day mouse biomarker study, SHLP3 raised IL-6 and MCP-1 alongside leptin—reason authors gave for lacking in vivo insulin sensitization despite in vitro adipocyte effects. animal
- Dose translation hazard: Multi-mg/kg mouse IP and μg ICV designs are not safe templates for human mcg SC charts. animal
- Variant mismatch: K4R research interest does not mean commercial “SHLP2” is K4R or that WT doses equal K4R. trial
- Hypoglycemia theoretical talk: Insulin-sensitizer framing (especially central SHLP2 clamp data) leads some researchers to mention glucose-monitoring caution if combined with diabetes drugs—speculative for exogenous SHLP self-experimentation, not a labeled interaction. forum
- CNS routes: ICV is lab-only; never a community self-admin path. animal
Evidence mix
More trial/lab tags than forum tags
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