Research goal
Covers compounds researched for their potential effects on aging biology — telomere maintenance, mitochondrial function, cellular senescence, and age-related metabolic decline.
| Compound | Class | Primary Mechanism | Commonly Reported For | Link |
|---|---|---|---|---|
| Epitalon | Tetrapeptide / epigenetic regulator | Telomerase activation; pineal gland peptide; melatonin regulation | Telomere length, sleep regulation, anti-aging | View profile → |
| GHK-Cu | Copper tripeptide | Activates tissue remodelling; anti-inflammatory; antioxidant gene expression | Skin aging, collagen synthesis, cellular repair | View profile → |
| SS-31 | Mitochondria-targeting peptide | Cardiolipin stabilisation on inner mitochondrial membrane; reduces ROS | Mitochondrial function, cardiac research, longevity | View profile → |
| MOTS-c | Mitochondria-derived peptide | AMPK activation; metabolic regulation; exercise mimetic properties | Metabolic health, insulin sensitivity, longevity | View profile → |
| NAD+ | Dinucleotide coenzyme (not a peptide) | Sirtuin activation; PARP repair; mitochondrial electron transport | Cellular energy, DNA repair, anti-aging | View profile → |
Contemporary longevity biology has converged on several interacting hallmarks of aging as research targets: telomere attrition, mitochondrial dysfunction, cellular senescence, and epigenetic dysregulation. Compounds on this page address different nodes within these hallmarks. Epitalon has been studied primarily in the context of telomere biology and epigenetic regulation of the pineal gland, with a body of research — largely from Russian laboratories — investigating its capacity to activate telomerase in somatic cell lines and to normalise age-related decline in melatonin secretion. GHK-Cu operates at the gene expression level, having been shown in transcriptomic studies to modulate hundreds of genes involved in tissue repair, antioxidant defence, and anti-inflammatory signalling, positioning it at the cellular maintenance axis of longevity research.
Mitochondrial dysfunction is increasingly recognised as a central driver of aging phenotypes rather than a secondary consequence. SS-31 (Elamipretide) addresses this directly through its affinity for cardiolipin, a phospholipid embedded in the inner mitochondrial membrane that is essential for organising the electron transport chain complexes responsible for ATP production. With aging, cardiolipin undergoes oxidative modification and redistribution, contributing to decreased respiratory efficiency and increased reactive oxygen species (ROS) generation. SS-31's mechanism — stabilising cardiolipin and reducing mitochondrial ROS — has been investigated in cardiac, renal, and skeletal muscle aging models, with several published human research trials in specific cardiovascular contexts.
NAD+ occupies a critical position in cellular metabolism and aging research due to its role as a substrate for sirtuins (NAD+-dependent deacetylases involved in epigenetic regulation and stress response) and for PARP enzymes that mediate DNA damage repair. Systemic NAD+ levels decline substantially with age, and this decline has been implicated in reduced sirtuin activity, impaired DNA repair capacity, and diminished mitochondrial function. MOTS-c is a more recently characterised mitochondria-derived peptide encoded within mitochondrial ribosomal RNA; research has investigated MOTS-c for its potential role in AMPK-mediated metabolic regulation and its exercise-mimetic properties in aged animal models, suggesting that mitochondria themselves may function as endocrine signalling organelles with systemic anti-aging effects.
Epitalon is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) derived from epithalamin, a pineal gland polypeptide preparation studied extensively by Vladimir Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology. Research has investigated Epitalon for its potential role in telomerase activation in human somatic cells, regulation of melatonin production in aging pineal tissue, and extension of lifespan in animal models. The Khavinson research program produced a substantial body of literature across several decades, including reported longevity extension in rodent studies and normalisation of circadian function in elderly human cohorts. Commonly reported protocols in the research context involve cyclical administration, with doses typically ranging from 5 to 10 mg per cycle.
GHK-Cu (glycyl-L-histidyl-L-lysine copper complex) is a naturally occurring copper-binding tripeptide found in human plasma, urine, and saliva at concentrations that decline significantly with age. Research has investigated GHK-Cu for its potential role in activating over 4,000 human genes involved in tissue repair, collagen synthesis, antioxidant enzyme production, and anti-inflammatory signalling — a breadth of transcriptomic influence unusual for a three-amino-acid peptide. Its most documented applications in research literature involve dermal aging and wound healing models, where it has been shown to stimulate collagen and glycosaminoglycan synthesis. Anecdotal reports suggest improvement in skin texture and healing, and it is commonly used topically in cosmetic research contexts as well as subcutaneously in more interventional protocols.
SS-31 (Elamipretide; also known as MTP-131 or Bendavia) is a tetrapeptide developed by Hazel Szeto and Peter Schiller, designed specifically to concentrate within the inner mitochondrial membrane via electrostatic interaction with cardiolipin. Research has investigated SS-31 for its potential role in preserving mitochondrial cristae architecture, reducing pathological ROS generation, and improving ATP synthesis efficiency in aged and diseased tissues. Human research trials have been conducted in heart failure with preserved ejection fraction (HFpEF), acute kidney injury, and Barth syndrome — a rare genetic cardiolipin disorder. Commonly reported doses in research trial contexts range from 0.05 to 0.25 mg/kg administered by infusion or subcutaneous injection.
MOTS-c is a 16-amino acid peptide encoded within the 12S ribosomal RNA region of the mitochondrial genome, making it one of a small class of mitochondria-derived peptides (MDPs) with endocrine signalling functions. Research has investigated MOTS-c for its potential role in AMPK pathway activation, regulation of glucose and lipid metabolism, and exercise-mimetic effects that attenuate age-related metabolic decline in rodent models. Circulating MOTS-c levels have been shown to decline with age and increase with physical exercise, suggesting it may function as a mitochondrial signal that coordinates systemic metabolic adaptation. Commonly reported doses in research animal models range from 5 to 15 mg/kg, with limited human pharmacokinetic data available at this stage.
NAD+ (nicotinamide adenine dinucleotide) is not a peptide but a dinucleotide coenzyme present in all living cells and essential to hundreds of metabolic reactions. It is included on this page because of its mechanistic overlap with longevity peptide research and its frequent co-investigation alongside peptide compounds in aging biology contexts. Research has investigated NAD+ repletion — typically via precursors such as NMN or NR rather than direct NAD+ administration — for its potential role in restoring sirtuin activity, improving PARP-mediated DNA repair fidelity, and recovering mitochondrial function in aged tissue. Intravenous NAD+ administration has been used in human research trial settings, with commonly reported doses ranging from 250 to 1000 mg per infusion session.
No established stack protocols documented for this goal at this time.
Is NAD+ actually a peptide?
No. NAD+ is a dinucleotide coenzyme — a small molecule composed of two nucleotides joined by a phosphate linkage — not a peptide or amino acid chain. It is included on this reference page because longevity researchers frequently investigate it alongside peptide compounds as part of a broader biological context, and because its mechanisms (sirtuin activation, PARP-dependent DNA repair, mitochondrial electron transport) intersect significantly with the pathways targeted by compounds like MOTS-c and SS-31. Understanding this distinction matters when evaluating research literature, as peptide and small-molecule pharmacology operate through fundamentally different routes and regulatory frameworks.
What does the research on Epitalon's telomerase mechanism actually show?
The primary evidence for Epitalon's telomerase-activating properties comes from in vitro studies published by the Khavinson research group, demonstrating that the tetrapeptide induced telomerase activity and telomere elongation in human fetal fibroblasts. Rodent longevity studies from the same group reported increased mean and maximum lifespan in treated animals. These findings, while intriguing, have not been widely independently replicated in peer-reviewed literature outside the originating institution, and human trial data remains limited. The mechanistic hypothesis — that an exogenous pineal-derived tetrapeptide can reproducibly activate telomerase in somatic tissue — is biologically plausible but awaits more rigorous independent validation before conclusions should be drawn about its magnitude of effect in humans.
How do SS-31 and MOTS-c differ in their mitochondrial targets?
SS-31 and MOTS-c address mitochondrial biology at distinct levels. SS-31 operates structurally — it accumulates within the inner mitochondrial membrane by binding cardiolipin, physically stabilising the membrane architecture required for electron transport chain efficiency and reducing the ROS that cardiolipin oxidation generates. MOTS-c operates as a signalling molecule — it is secreted from mitochondria into the cytoplasm and nucleus, where it activates AMPK and regulates gene expression programs governing glucose uptake, fatty acid oxidation, and stress response. In simplified terms, SS-31 is a membrane-level structural intervention while MOTS-c is a mitochondria-originating hormone with systemic metabolic effects; they are complementary rather than redundant research targets.
Are these longevity compounds typically researched together or independently?
In formal research settings, these compounds are almost exclusively studied independently in controlled single-agent trials, as combination protocols introduce confounding variables that make mechanistic conclusions impossible to draw. Anecdotal reports from self-experimenting researchers describe combinations of NAD+ precursors, Epitalon, and GHK-Cu within broader longevity regimens, but no controlled combination trial data exists to characterise interaction effects, altered pharmacokinetics, or additive versus synergistic outcomes. The compounds target sufficiently different biological axes — telomere maintenance, mitochondrial membrane integrity, gene expression remodelling, coenzyme repletion — that in principle they are not directly redundant, but this reasoning is not a substitute for combination safety and efficacy data.