⚡
SS-31
CARDIOLIPIN / ETC
Protects the structural integrity of the electron transport chain at the inner mitochondrial membrane
🔄
MOTS-c
AMPK / MITOPHAGY
Activates the master metabolic switch — triggers mitochondrial quality control and energy sensing
🧬
5-Amino-1MQ
NAD⁺ / SIRT1
Elevates intracellular NAD⁺ by blocking its consumption — fuels the enzymatic machinery of the ETC and sirtuins
01 — Overview
What Is the Mitochondrial Reset
The Mitochondrial Reset is a focused 10–12 week three-peptide block targeting the three most mechanistically distinct and non-redundant points of mitochondrial dysfunction. It is designed to be run as a standalone protocol or as Tier 2 of the full Longevity Stack — twice per year, in Q1 and Q3.
Each compound in the stack addresses a completely different cellular target. SS-31 works at the structural level — protecting cardiolipin and restoring ETC supercomplex architecture. MOTS-c works at the signaling level — activating AMPK to drive mitochondrial quality control, mitophagy, and metabolic flexibility. 5-Amino-1MQ works at the substrate level — elevating NAD⁺ by blocking the enzyme that consumes it in fat tissue, fueling everything else in the chain.
Together they address the three primary reasons mitochondria fail with aging: structural membrane degradation, impaired quality control signaling, and declining fuel substrate availability. No other combination in the research peptide space covers all three simultaneously.
02 — The Problem
Why Mitochondrial Decline Drives Aging
Mitochondrial dysfunction is not just a symptom of aging — accumulating evidence positions it as a primary driver. As mitochondria fail, ATP production drops, ROS increases, NAD⁺ declines, and the cellular energy budget that powers every repair process in the body shrinks. This creates a self-reinforcing spiral: less energy → less repair → more damage → less energy.
The three specific failure modes this stack addresses:
CARDIOLIPIN LOSS
The phospholipid scaffold that organizes ETC supercomplexes oxidizes and fragments with age — causing electron leakage, ROS production, and ATP inefficiency. SS-31 addresses this directly.
AMPK DECLINE
AMPK — the energy sensor that triggers mitophagy (clearing damaged mitochondria) and new mitochondrial biogenesis — becomes less responsive with age. Dysfunctional mitochondria accumulate rather than being replaced. MOTS-c restores this signal.
NAD⁺ COLLAPSE
NAD⁺ levels drop 50%+ between age 40 and 60. Sirtuins (SIRT1–3) that regulate mitochondrial biogenesis, repair, and stress resistance are NAD⁺-dependent. Without adequate NAD⁺, these longevity enzymes can't function. 5-Amino-1MQ restores the pool.
03 — The Three Compounds
Mechanism Deep Dive
TARGET 1 — STRUCTURE
SS-31
CARDIOLIPIN → ETC
Selectively concentrates in the inner mitochondrial membrane. Binds cardiolipin — preventing oxidation and preserving the lipid scaffold that holds ETC supercomplexes together. Restores ATP synthesis efficiency and reduces pathological ROS.
TARGET 2 — SIGNALING
MOTS-c
AMPK → MITOPHAGY
Mitochondria-encoded peptide. Activates AMPK → triggers mitophagy (clearance of damaged mitochondria) and biogenesis of new ones. Regulates the folate-methionine cycle. Exercise mimetic — rises with physical activity; declines with age and inactivity.
TARGET 3 — FUEL
5-Amino-1MQ
NNMT → NAD⁺ → SIRT1
Blocks NNMT in adipose tissue — the enzyme that consumes SAM and depresses NAD⁺ precursor availability. Elevating NAD⁺ activates SIRT1/SIRT3, which deacetylate and activate key mitochondrial enzymes, PGC-1α, and DNA repair proteins.
▸ SYNERGISTIC INTERACTIONS — WHY ALL THREE TOGETHER
SS-31 + NAD⁺ (5-Amino-1MQ)
SS-31 restores ETC structural integrity; NAD⁺ provides the electron carrier substrate for Complex I that the restored ETC needs to function efficiently. Structure without fuel, or fuel without structure — neither alone achieves full mitochondrial restoration.
MOTS-c + SS-31
MOTS-c's AMPK activation triggers mitophagy — clearing damaged mitochondria. SS-31 simultaneously protects the healthy mitochondria that remain. Together they execute a quality-control reset: remove the damaged, protect the functional.
NAD⁺ + MOTS-c
AMPK and sirtuins are synergistic partners — AMPK elevates NAD⁺ through its own pathways; NAD⁺ activates SIRT1 which deacetylates and activates LKB1 (the AMPK kinase). A positive feedback loop: 5-Amino-1MQ raising NAD⁺ amplifies MOTS-c's AMPK signal.
04 — Block Protocol
The 12-Week Reset Block
WEEKS 1–2
Load
Start all three at low end of dose range. Allow body to adapt. Monitor for any unexpected responses. Energy dip common in week 1–2 as mitophagy begins clearing damaged mitochondria.
WEEKS 3–10
Core Block
Titrate to full working doses by week 3. This is where the structural and signaling reset occurs. Most users report measurable improvements in energy, exercise capacity, and sleep quality from week 4–6 onward.
WEEKS 11–12
Maintain
Hold at working doses. Run final biomarker panel at week 12 to capture end-of-cycle data. Do not taper — simply complete the cycle and enter the break period.
WEEKS 13–20
Break
6–8 week break. The mitochondrial structural and signaling changes achieved persist well into the off period. Use this time for the Q2 tissue maintenance layer (Glow/Klow).
| Compound | Starting Dose | Working Dose | Route | Frequency | Timing |
|---|
| SS-31 | 5–10 mg | 10–30 mg | SC | Daily | AM — either fed state |
| MOTS-c | 50 mcg | 100–300 mcg | SC | 3–5×/week | AM fasted / pre-workout |
| 5-Amino-1MQ | 50 mg | 100–200 mg | Oral | Daily | AM with food |
The week 1–2 energy dip is expected and is mechanistically meaningful — MOTS-c-driven AMPK activation triggers mitophagy, temporarily increasing cellular energy demand as dysfunctional mitochondria are cleared. This typically resolves by week 3 and is followed by a noticeable improvement in baseline energy. If the dip is severe, reduce MOTS-c dose and titrate more gradually. SS-31 and 5-Amino-1MQ do not typically cause this — it is MOTS-c-specific.
05 — Individual Protocols
Per-Compound Protocol Details
MECHANISM
Penetrates IMM via electrostatic attraction to cardiolipin. Prevents cardiolipin peroxidation — preserving the lipid scaffold that organizes Complexes I, III, IV into supercomplexes for efficient electron transfer. Reduces cytochrome c release. Reverses cristae architecture collapse. Nature Aging 2021: reversed cardiac aging in mice within weeks.
PROTOCOL
DOSE10–30 mg/day
ROUTESC injection
FREQUENCYDaily
TIMINGAM — either fed state
HALF-LIFE~30 min plasma
NOTEMitochondrial retention prolonged despite short plasma t½
MECHANISM
Encoded in mitochondrial DNA — the first mitochondria-derived peptide with systemic metabolic effects. Translocates to nucleus under metabolic stress. Activates AMPK → triggers mitophagy, PGC-1α-driven biogenesis, and GLUT4 translocation for insulin-independent glucose uptake. Regulates folate-methionine cycle. Centenarian studies: elevated in exceptionally long-lived individuals.
PROTOCOL
DOSE100–300 mcg
ROUTESC injection
FREQUENCY3–5×/week
TIMINGAM fasted / pre-workout
NOTEPre-workout timing mimics natural exercise-induced MOTS-c surge
MECHANISM
Selective NNMT inhibitor — blocks the enzyme in adipose tissue that consumes SAM and suppresses NAD⁺ precursor availability. Unlike NMN/NR which add NAD⁺ precursors, 5-Amino-1MQ stops their consumption. Raises intracellular NAD⁺ → activates SIRT1 → promotes fat oxidation, mitochondrial biogenesis, and DNA repair. Animal studies: 7–10% body fat reduction without caloric restriction.
PROTOCOL
DOSE100–200 mg/day
ROUTEOral capsule
FREQUENCYDaily (1–2× split)
TIMINGAM with food
MONITORHomocysteine / SAM:SAH ratio
06 — Storage
Reconstitution & Storage — All Three
| Compound | Dry (Lyophilized) | Reconstituted | Shelf Life (Recon) | Special Notes |
|---|
| SS-31 | –20°C freezer | 36–46°F / 2–8°C fridge | 4–6 weeks | Light-sensitive; no freeze-thaw once reconstituted |
| MOTS-c | –20°C freezer | 36–46°F / 2–8°C fridge | 4–6 weeks | Stable small peptide; handle gently |
| 5-Amino-1MQ | Room temp (sealed) | N/A — oral capsule | 12–24 months | Protect from moisture and heat; no refrigeration required for capsules |
SS-31 and MOTS-c require full cold chain. 5-Amino-1MQ as an oral small molecule is significantly more stable — capsules can be kept at room temperature. Reconstitute SS-31 and MOTS-c separately with BAC water; they can be drawn into the same syringe for a single daily injection on days when both are dosed.
07 — Monitoring
Biomarkers — Before, Week 6, Week 12
Run baseline before starting, mid-cycle at week 6, and end-of-cycle at week 12. These are the most direct indicators of mitochondrial function improvement available through commercial labs.
▸ Primary Mitochondrial Markers
| Biomarker | Lab Test | Clinical Range | Goal on Protocol |
|---|
NAD⁺ (Intracellular)
5-Amino-1MQ primary marker | Jinfiniti Intracellular NAD⁺ | CLINICALNo standard reference | GOAL>40 µM whole blood; expect measurable rise from week 4 |
CoQ10 (Ubiquinol)
ETC function cofactor | Plasma CoQ10 | CLINICAL0.4–1.9 µg/mL | GOAL1.5–3.5 µg/mL; trending up on SS-31 + MOTS-c |
GDF-15
Mitochondrial stress signal | Serum GDF-15 | CLINICAL<1200 pg/mL | GOAL<400 pg/mL; declining trend = reduced mito stress |
Resting Lactate
Aerobic efficiency marker | Serum Lactate (resting) | CLINICAL0.5–2.2 mmol/L | GOAL0.5–1.0 mmol/L; declining = improved aerobic metabolism |
▸ Oxidative Damage
| Biomarker | Lab Test | Clinical Range | Goal on Protocol |
|---|
8-OHdG
Oxidative DNA damage | Urine 8-OHdG | CLINICAL<15 ng/mg creatinine | GOAL<5 ng/mg creatinine; SS-31 reduces pathological ROS |
Oxidized LDL
Lipid peroxidation | Serum oxLDL | CLINICAL<60 U/L | GOAL<40 U/L; declining on mito reset |
▸ Metabolic Response
| Biomarker | Lab Test | Clinical Range | Goal on Protocol |
|---|
HOMA-IR
Insulin resistance — MOTS-c target | Fasting glucose + insulin (calculated) | CLINICAL<2.0 | GOAL<1.0; expect improvement from MOTS-c AMPK activation |
Triglycerides
5-Amino-1MQ fat oxidation marker | Lipid Panel | CLINICAL<150 mg/dL | GOAL<80 mg/dL; declining on 5-Amino-1MQ + MOTS-c |
| Fasting Glucose | Fasting Blood Glucose | CLINICAL70–99 mg/dL | GOAL75–90 mg/dL |
▸ Methylation (5-Amino-1MQ Specific)
| Biomarker | Lab Test | Clinical Range | Goal on Protocol |
|---|
Homocysteine
Methylation cycle proxy | Serum Homocysteine | CLINICAL<15 µmol/L | GOAL5–8 µmol/L; NNMT inhibition affects methionine cycle — monitor |
| SAM:SAH Ratio | Plasma SAM/SAH (specialty) | CLINICALSAM/SAH >4.5 | GOAL>6.0; 5-Amino-1MQ should improve this ratio |
▸ Safety
| Biomarker | Lab Test | Clinical Range | Goal |
|---|
| AST / ALT | CMP | CLINICALAST 10–40 / ALT 7–56 U/L | GOALAST <26 / ALT <26; stable throughout |
| CBC | Complete Blood Count | CLINICALStandard ranges | GOALMid-range; WBC 4.5–6.0; stable |
⚠ None of the three compounds in this stack are FDA-approved for the indications listed. 5-Amino-1MQ has no published human clinical trials — monitor homocysteine and SAM:SAH closely, especially in individuals with MTHFR variants or elevated baseline homocysteine. SS-31 had Phase 2/3 clinical trials but did not receive final approval. MOTS-c has early human data from aging studies. Work with a qualified practitioner.
08 — Summary
Mitochondrial Reset at a Glance
MITOCHONDRIAL RESET — PROTOCOL SUMMARY
SS-31 + MOTS-c + 5-Amino-1MQ | Three Targets: Cardiolipin · AMPK · NAD⁺
Wk 1–2 dip
EXPECT MITO ADAPT
NAD⁺ / GDF-15
PRIMARY MARKERS
READY TO RUN THIS PROTOCOL?
Build Your Mitochondrial Reset Stack
Add SS-31, MOTS-c, and 5-Amino-1MQ to your personal tracker with a single click — cycle timer, dose calculator, and daily log included.
OPEN MY PROTOCOL TRACKER →