Protocolsβ€ΊMitochondrial Peptide Triad (Research)
AdvancedLongevityOngoing

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.

Patient profile: Research context only. Adults 55+ with documented mitochondrial decline indicators: elevated lactate/pyruvate ratio, low mtDNA copy number, age-related metabolic syndrome, or early neurodegeneration markers.

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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

Primary

Dose

Experimental β€” not established in humans

Frequency

3x/week SC (research protocol)

Timing

Morning

Duration

8 weeks on / 4 weeks off

MOTS-c

Supporting

Dose

5–10 mg

Frequency

3x/week SC

Timing

Pre-exercise or morning

Duration

8 weeks on / 4 weeks off

Humanin

Optional

Dose

2–4 mg

Frequency

3x/week SC

Timing

Evening

Duration

8 weeks on / 4 weeks off

Monitoring Parameters

  • βœ“Mitochondrial function proxy: lactate/pyruvate ratio, plasma acylcarnitines
  • βœ“Metabolic panel: fasting glucose, insulin (HOMA-IR), HbA1c β€” baseline and every 8 weeks
  • βœ“Inflammatory markers: IL-6, TNF-alpha, hs-CRP
  • βœ“Cognitive function: MoCA score, reaction time testing
  • βœ“Retinal OCT (optional, for macular degeneration research arm)
  • βœ“mtDNA copy number (if lab access available)
  • βœ“Body composition (DEXA) β€” baseline and every 16 weeks

Expected Outcomes

1

Weeks 1–4: Improved energy metabolism markers (reduced fasting lactate), enhanced exercise capacity

2

Weeks 4–8: Reduction in inflammatory cytokines; potential improvement in insulin sensitivity (MOTS-c primary driver)

3

Cycle 2 (weeks 12–20): Cumulative anti-apoptotic effect; cognitive function testing may show measurable improvement

4

Long-term: Theoretical slowing of mtDNA copy number decline; reduced all-cause neurodegeneration risk

Contraindications

  • βœ—TIER 4 β€” SHLP2 and Humanin have no established human dosing. For research/educational purposes only.
  • βœ—Active malignancy (anti-apoptotic peptides may theoretically protect cancer cells)
  • βœ—Mitochondrial myopathies with unknown mutation status
  • βœ—Pregnancy and breastfeeding
  • βœ—Concurrent 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.