Mitochondrial Peptide Triad (Research)
Restore mitochondrial signaling using three endogenous mitochondrial-derived peptides β SHLP2, MOTS-c, and Humanin β to reduce cellular apoptosis, improve metabolic efficiency, and support neuronal and retinal resilience in aging.
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This protocol is an educational example only. It does not apply to your specific health situation. Medical supervision is required. Peptide therapy is not approved by regulatory bodies for many of the described indications.
Protocol Stack
SHLP2
PrimaryDose
Experimental β not established in humans
Frequency
3x/week SC (research protocol)
Timing
Morning
Duration
8 weeks on / 4 weeks off
MOTS-c
SupportingDose
5β10 mg
Frequency
3x/week SC
Timing
Pre-exercise or morning
Duration
8 weeks on / 4 weeks off
Humanin
OptionalDose
2β4 mg
Frequency
3x/week SC
Timing
Evening
Duration
8 weeks on / 4 weeks off
Monitoring Parameters
- βMitochondrial function proxy: lactate/pyruvate ratio, plasma acylcarnitines
- βMetabolic panel: fasting glucose, insulin (HOMA-IR), HbA1c β baseline and every 8 weeks
- βInflammatory markers: IL-6, TNF-alpha, hs-CRP
- βCognitive function: MoCA score, reaction time testing
- βRetinal OCT (optional, for macular degeneration research arm)
- βmtDNA copy number (if lab access available)
- βBody composition (DEXA) β baseline and every 16 weeks
Expected Outcomes
Weeks 1β4: Improved energy metabolism markers (reduced fasting lactate), enhanced exercise capacity
Weeks 4β8: Reduction in inflammatory cytokines; potential improvement in insulin sensitivity (MOTS-c primary driver)
Cycle 2 (weeks 12β20): Cumulative anti-apoptotic effect; cognitive function testing may show measurable improvement
Long-term: Theoretical slowing of mtDNA copy number decline; reduced all-cause neurodegeneration risk
Contraindications
- βTIER 4 β SHLP2 and Humanin have no established human dosing. For research/educational purposes only.
- βActive malignancy (anti-apoptotic peptides may theoretically protect cancer cells)
- βMitochondrial myopathies with unknown mutation status
- βPregnancy and breastfeeding
- βConcurrent mitochondria-targeting chemotherapy (e.g., high-dose metformin)
Clinical Notes
All three peptides β SHLP2, MOTS-c, and Humanin β are encoded in overlapping reading frames of mitochondrial 12S and 16S rRNA, making them a biologically coherent family. Their effects are complementary: MOTS-c acts primarily on nuclear AMPK pathways and glucose metabolism; Humanin inhibits the pro-apoptotic BAX protein and protects neurons; SHLP2 reduces mitochondrial ROS and supports retinal/neuronal survival. This protocol represents the first conceptual attempt to stack all three in a single therapeutic model. MOTS-c is the most studied of the three (Tier 3) β it anchors the protocol's evidence base. The 8-weeks-on/4-weeks-off cycle is borrowed from analogous mitochondrial support protocols and prevents receptor desensitisation.
Case Study
Clinical Practice Example
Female, 61, presenting with progressive fatigue, mild cognitive complaints (MoCA 24/30), impaired glucose tolerance (fasting glucose 6.2 mmol/L, HOMA-IR 3.8), and plasma lactate 2.4 mmol/L (mildly elevated). Enrolled in hypothetical longitudinal research protocol. Baseline mtDNA copy number: 180 copies/cell (low for age). After 8-week cycle with MOTS-c + SHLP2 + Humanin: fasting glucose 5.4 mmol/L, HOMA-IR 2.1, lactate 1.6 mmol/L. MoCA 27/30 at week 12. Self-reported energy 8/10 vs. 4/10 at baseline. Note: Hypothetical educational case β SHLP2 has no published human trial data.