Longevity Peptides: Epithalon, MOTS-c, NAD+ and More

Longevity peptides focus on the mechanisms at the core of aging, including telomeres, mitochondria, NAD+ production, and the pathways associated with exercise. The studies supporting this research reach back to studies performed years ago and others that have just been revealed. This article provides documentation supporting this work across companies and shows where the evidence is scarce.

What Longevity Peptides Target

Telomerase and Cellular Aging

Telomeres are extensions at the ends of a chromosome that shorten over time. When they become adjoined to a shorter threshold, cells cease to divide and die. Telomerase is the enzyme that can elongate telomeres. Epithalon is being investigated for its capability of stimulating telomerase. The assumption is that restoring the function of telomerase may impact cellular aging, although the association between telomeres and organismal aging is rather complex and far from being straightforward.

Mitochondrial Function

MOTS-c is a mitochondrial-derived peptide, it is encoded in the mitochondrial genome rather than the nuclear genome. Published research suggests MOTS-c plays a role in metabolic homeostasis, insulin sensitivity and exercise physiology. A 2018 study in Cell Metabolism demonstrated that MOTS-c treatment improved exercise capacity in mice. The mitochondrial origin of this peptide makes it biologically distinct from the synthetic peptides in other categories.

NAD+ Metabolism

NAD+ (which stands for nicotinamide adenine dinucleotide) is a coenzyme that is important for cellular metabolism, DNA repair, and sirtuin activation. With aging, the levels of NAD+ decrease, and restoring them is an area of concern in the field of aging research. Even though NAD+ is not a peptide, it appears in catalogs of peptide vendors along with NMN (nicotinamide mononucleotide) and is supplied using injections in research studies. The company Real Peptides offers injectable NAD+ as part of their offer.

Epithalon: Telomerase Research

Khavinson Studies on Pineal Peptides

Epithalon (also spelled Epitalon) is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) designed to mimic the natural peptide Epithalamin, which is produced by the pineal gland. The primary research on Epithalon comes from the laboratory of Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology. A 2003 study by Anisimov et al. in Biogerontology reported that repeated courses of Epithalon treatment in mice were associated with telomerase activation in somatic cells and modest lifespan extension.

Published In Vitro and Animal Data

In vitro studies show that Epithalon activates telomerase in human fetal fibroblast cell cultures. Animal studies report effects on melatonin secretion, reproductive function in aging rats and lifespan markers. The body of evidence is smaller and less independently replicated than BPC-157's, most published Epithalon data originates from a single research group. This is an important caveat when evaluating the strength of the evidence. Limited human data exists from early Russian studies with small sample sizes.

MOTS-c: Mitochondrial-Derived Peptide

Exercise Mimetic Research

The 2018 Cell Metabolism study demonstrated that MOTS-c improved physical performance in mice subjected to exercise testing, earning it the label "exercise mimetic" in popular science coverage. The mechanism involves activation of AMPK (AMP-activated protein kinase), a master metabolic regulator that coordinates glucose uptake, fatty acid oxidation and mitochondrial biogenesis. MOTS-c treatment in mice improved treadmill endurance and glucose disposal during exercise.

Metabolic Studies in Mouse Models

In addition to the effects of exercise, published studies on the peptide MOTS-c show remarkable results on insulin sensitivity and diet-induced obesity in mouse studies. A 2015 study in Cell Metabolism first characterized MOTS-c as a mitochondrial-derived peptide that regulates metabolic homeostasis and prevents insulin resistance in mice, which is brought about by age and diet. There is a lack of sufficient human experiments in the studies on the peptide MOTS-c.

NAD+ Supplementation Research

Precursor vs Direct Administration

One can increase their NAD+ levels either by the oral precursor which is NMN and NR or through IV or subcutaneous injection of NAD+. The oral precursors cause the transfer of the NMN into NAD+ through a series of reactions. Since direct injection does not require conversion into the NAD+ form, it includes the cold-chain management. There remains lack of consensus in scientific discussions on the actual efficiency of both methods of delivery, although the study data suggest that both oral and injectable methods can give results.

Published Dose-Response Data

Human studies on NMN supplements have involved doses ranging from 250 to 1,200 mg daily, but the outcomes have shown significant increases in plasma levels of NAD+ metabolites. On the other hand, injectable NAD+ protocols are defined only in a speculative manner in literature. Some companies like Real Peptides market injectable forms of NAD+. Research on NAD+ is among the most active areas in the field of anti-aging studies, with many clinical trials currently ongoing.

SLU-PP-332: Exercise Mimetic Compound

Mechanism and Early Data

SLU-PP-332 is an ERRα/ERRγ agonist (estrogen-related receptor alpha/gamma) studied for exercise-mimetic properties. It is not a peptide in the strict sense but appears in peptide vendor catalogs as part of the longevity and performance research category. Published data is early, the compound was characterized in preclinical studies showing effects on muscle fiber type switching and endurance markers in mice. Real Peptides offers SLU-PP-332 at the highest price point in this category ($84.00), reflecting both the novelty of the compound and limited supply.