Comparison. Research use only.
MOTS-c vs NAD+
MOTS-c and NAD+ both sit at the centre of mitochondrial and metabolic-aging research, which is why they are often mentioned together. They are different kinds of molecule entirely: MOTS-c is a 16-residue peptide encoded by mitochondrial DNA that signals through AMPK, while NAD+ is a dinucleotide cofactor that carries electrons and is consumed by sirtuins, PARPs and CD38.
What is the difference between MOTS-c and NAD+?
MOTS-c is a 16-amino-acid peptide encoded by mitochondrial DNA that activates AMPK through the folate cycle; NAD+ is not a peptide but a redox cofactor that carries electrons and is consumed by sirtuins, PARPs and CD38. MOTS-c's evidence is preclinical, with human data limited to exercise observations and preliminary pharmacokinetics. NAD+ human trials tested precursors and mostly reported null functional results.
| Attribute | MOTS-c | NAD+ |
|---|---|---|
| Molecule class | Mitochondrial-derived peptide (16 amino acids) | Dinucleotide redox cofactor (not a peptide) |
| Molecular weight | 2174.5 Da | 663.43 g/mol (free acid) |
| Origin | Encoded in the 12S rRNA gene of mitochondrial DNA; discovered by Lee et al. (2015) | Endogenous metabolite made via salvage, de novo and Preiss-Handler pathways |
| Proposed mechanism | Inhibits ATIC in the folate cycle; AICAR accumulates and activates AMPK | Electron carrier in glycolysis, TCA cycle and beta-oxidation; substrate for sirtuins, PARPs and CD38 |
| Human evidence | Exercise induced endogenous MOTS-c (Reynolds et al., 2021); trial data limited to preliminary pharmacokinetics | Precursor trials with nicotinamide riboside (Martens 2018; Dollerup 2018; Elhassan 2019) |
| Regulatory status | Investigational; no approved use; not on the WADA list | Not an approved drug; endogenous metabolite and laboratory reagent |
What is MOTS-c?
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid mitochondrial-derived peptide (MDP). It is encoded within a previously unrecognized open reading frame in the 12S rRNA gene of the mitochondrial genome.
Read the full MOTS-c research summary →What is NAD+?
NAD+ is a redox cofactor, a molecule cells use to shuttle electrons. It cycles between an oxidized and a reduced state, accepting a hydride at the C4 position of its nicotinamide ring.
Read the full NAD+ research summary →MOTS-c and NAD+ specifications
Frequently asked questions
Is NAD+ a peptide like MOTS-c?
No. MOTS-c is a 16-amino-acid peptide, notable as a regulatory peptide encoded by mitochondrial rather than nuclear DNA (Lee et al., Cell Metabolism 2015). NAD+ (nicotinamide adenine dinucleotide) is a dinucleotide cofactor present in every cell, where it carries electrons in glycolysis and the TCA cycle. MOTS-c and NAD+ are grouped together because both are central to mitochondrial and metabolic-aging research.
Do MOTS-c and NAD+ act through the same pathway?
No. MOTS-c inhibits the folate-cycle enzyme ATIC, which lets AICAR accumulate and activate AMPK, the cell's energy sensor; under stress it also moves to the nucleus and switches on Nrf2-driven genes. NAD+ works as a redox carrier and as a substrate that sirtuins, PARPs and CD38 consume. The two pathways intersect in energy metabolism but are not the same mechanism.
Have MOTS-c and NAD+ been studied in humans?
Only partially. For MOTS-c, Reynolds et al. (Nature Communications 2021) reported that exercise raised endogenous MOTS-c in human muscle and blood, and human trial data are limited to preliminary pharmacokinetic studies. Human NAD+ trials mostly tested precursors such as nicotinamide riboside; they raised measured NAD+ levels but reported null results on functional endpoints such as insulin sensitivity (Dollerup et al., 2018).
What is the regulatory status of MOTS-c and NAD+?
MOTS-c is an investigational peptide with no approved therapeutic use in any jurisdiction, and it is not currently on the WADA prohibited list. NAD+ is an endogenous metabolite and common laboratory reagent, not an approved drug, and intravenous NAD+ preparations are unapproved drug products. Veridian supplies both MOTS-c and NAD+ strictly for in vitro and non-human research.
Other research peptide comparisons
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