Why these four sit together
They share a catalogue heading and not much else. Two were developed in Russian institutes and have most of their literature in Russian; one was discovered in a Californian ageing laboratory in 2015; one is a metabolite present in every living cell. The useful comparison is by origin, by what has been measured, and by how much of that measurement was done in humans.
Side by side
| Compound | What it is | Origin | Models in the cited papers | Human evidence and status |
|---|---|---|---|---|
| Semax | Heptapeptide Met-Glu-His-Phe-Pro-Gly-Pro: the ACTH(4-10) fragment with a Pro-Gly-Pro tail that slows its breakdown | Institute of Molecular Genetics, Russian Academy of Sciences | Rat hippocampus and basal forebrain: BDNF and trkB expression (Dolotov 2006, two papers) | Registered as a medicine in Russia as a nasal solution. Not approved in the United States or the European Union; clinical literature is largely Russian-language. |
| Epithalon | Tetrapeptide Ala-Glu-Asp-Gly, a synthetic analogue of a pineal-gland extract | St Petersburg Institute of Bioregulation and Gerontology (Khavinson) | Human fetal fibroblast cultures: telomerase activity (Khavinson 2003); female SHR mice: ageing biomarkers and tumour incidence over the lifespan (Anisimov 2003) | Human reports exist only in the Russian literature from the originating group. Not approved anywhere. |
| MOTS-c | 16-residue peptide encoded in the 12S rRNA region of mitochondrial DNA, one of the mitochondrial-derived peptides | Discovered 2015 in the Cohen laboratory, University of Southern California | Mice on a high-fat diet: prevented obesity and insulin resistance, acting on skeletal muscle through AMPK (Lee 2015) | A synthetic analogue developed by a biotechnology company has been through phase 1 trials. MOTS-c itself is not approved anywhere. |
| NAD+ | Nicotinamide adenine dinucleotide, a coenzyme of cellular redox reactions. Not a peptide. | Endogenous; first described in 1906 as a yeast fermentation cofactor | The cited papers are reviews of the ageing and precursor literature (Covarrubias 2021, Yoshino 2018, Rajman 2018) | Oral precursors (NMN, NR) have been in small human trials. NAD+ itself is not an approved drug; its use in clinics is outside any trial evidence. |
What the cited studies found
Semax
Dolotov and colleagues published two papers in 2006. In rat hippocampus, Semax raised the expression of brain-derived neurotrophic factor and its receptor trkB. In rat basal forebrain, it bound specifically to membrane preparations and raised BDNF protein levels. Those are mechanism studies in rodents. The compound's clinical record is a Russian one, and we do not summarise trials we cannot cite from an indexed journal.
Epithalon
Khavinson and colleagues (2003) reported that the tetrapeptide induced telomerase activity and telomere elongation in cultured human fetal fibroblasts. Anisimov and colleagues (2003) followed female SHR mice over their lifespan and reported slowed ageing biomarkers and fewer spontaneous tumours. Both come from the originating group; independent replication is thin.
MOTS-c
Lee and colleagues (2015, Cell Metabolism) identified the peptide, showed it is encoded within the mitochondrial genome, and found that in mice it acted on skeletal muscle through the AMPK pathway and the folate–methionine cycle, preventing diet-induced obesity and insulin resistance. Later work from the same field links it to exercise; we cite only the discovery paper because it is the one we verified.
NAD+
The three cited reviews cover the same ground from different angles: NAD+ levels decline with age, the enzymes that consume it (PARPs, CD38, sirtuins) are known, and raising it with precursors has been tested mostly in animals with small human trials of NMN and NR. None of the reviews is a trial of NAD+ itself, and none should be read as one.
Handling notes for this group
- Semax begins with methionine, which oxidises in solution. Keep reconstituted material dark and capped.
- MOTS-c contains two methionines, a tryptophan and two tyrosines: the most oxidation- and light-sensitive sequence in our catalog. Reconstitute what will be used, store solutions dark and cold, and aliquot rather than re-open.
- Epithalon has no oxidation-prone residues. It does contain an aspartate–glycine pair, which can isomerise through a succinimide intermediate in solution; keep solutions cold and use them promptly.
- NAD+ is hygroscopic and hydrolyses in solution, faster warm and at alkaline pH. Keep the powder sealed and cold, prepare solutions fresh, and expect the certificate to report content rather than a purity percentage, because NAD+ is assayed as a small molecule rather than a peptide.
- All four ship as dry solids and are stored at −20°C. Storage horizons by form are on the storage guide; the sequence-specific notes above are also printed on each product page.
In our catalog
Semax, Epithalon, MOTS-c and NAD+, each with specifications, the references above with PubMed links, and the certificate for the lot in stock where one exists.