Mechanism: Mitochondrial

    MOTS-c vs NAD+: Mitochondrial Mechanism Comparison

    Both target mitochondrial function, the cornerstone of healthy ageing research. MOTS-c is a 16 amino acid mitochondrial derived peptide, NAD+ is a coenzyme central to energy metabolism.

    Side-by-side comparison

    AttributeMOTS-cNAD+
    ClassMitochondrial derived peptideCoenzyme
    MechanismAMPK activation, insulin sensitivitySirtuin and PARP substrate, redox balance
    RouteSubcutaneous injectionInjection, IV, or oral precursors (NR, NMN)
    Strongest evidenceRodent insulin sensitivity, exercise mimeticRodent lifespan, human metabolic markers with NR
    Typical research dose5 to 10 mg weekly100 to 500 mg IV or 250 to 500 mg oral precursor

    Key differences

    • ·MOTS-c is a peptide signal that activates AMPK and metabolic homeostasis
    • ·NAD+ is a substrate consumed by sirtuins and PARPs
    • ·MOTS-c declines with age in human plasma (Lee et al. 2015)
    • ·NAD+ declines tissue wide with age, supplementation strategies include precursors NR and NMN

    Research summary

    Lee et al. (2015) characterised MOTS-c as an insulin sensitiser and metabolic regulator. Martens et al. (2018) showed NR raised NAD+ in humans with modest cardiovascular markers. Both target ageing biology but through orthogonal pathways and can be researched in parallel.

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