Anti-Aging

Cardiogen is a synthetic tetrapeptide Ala-Glu-Asp-Arg (AEDR), developed as a cardiac muscle bioregulator by the Khavinson group at the St. Petersburg Institute of Bioregulation and Gerontology. It is derived from bovine cardiac tissue and proposed to promote cardiomyocyte survival and proliferation through epigenetic mechanisms. Cardiogen's research evidence consists of organotypic rat myocardial culture experiments demonstrating cardiomyocyte proliferation and anti-apoptotic effects at picomolar concentrations — results reported in review articles by the developing research group. No independent replication, Western peer-reviewed animal studies, or human clinical trials have been published.

Cartalax (Ala-Glu-Asp) is a synthetic tripeptide developed by Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology as part of the bioregulator peptide program. It belongs to a class of ultra-short peptides (2-4 amino acids) that Khavinson's group has investigated for tissue-specific regulatory effects over several decades. Cartalax was designed to target cartilage and musculoskeletal tissue, with the aim of preserving cartilage integrity and promoting chondrocyte function during aging. The bioregulator peptide concept posits that short peptides can interact directly with DNA through sequence-specific binding to the minor groove, influencing gene expression without requiring membrane receptor activation. This is a non-conventional mechanism for peptide action and remains an area of active research, primarily within Russian academic institutions. Cartalax is part of a larger family of Khavinson peptides that includes Epitalon (AEDG), Pinealon (EDR), and others, each claimed to have tissue-specific tropism.

Epitalon (also spelled Epithalon) is a synthetic tetrapeptide with the sequence Ala-Glu-Asp-Gly, developed by Professor Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology in Russia. It is the synthetic analogue of Epithalamin, a peptide extract derived from the bovine pineal gland that was studied for its anti-aging properties beginning in the 1980s. Epitalon was designed to reproduce the biological activity of Epithalamin in a defined, reproducible synthetic form. The primary research interest in Epitalon centers on its reported ability to activate telomerase, the enzyme responsible for maintaining telomere length at chromosome ends. Telomere shortening is a hallmark of cellular aging, and interventions that preserve telomere length have been hypothesized to extend cellular and organismal lifespan. While Epitalon research has generated intriguing in vitro and animal data, the evidence base consists primarily of studies from a single research group, and no large-scale clinical trials have been conducted outside of Russia.

FOXO4-DRI is a synthetic all-D-amino acid retro-inverso peptide that acts as a senolytic agent — a compound that selectively triggers apoptosis in senescent cells while sparing non-senescent tissue. It was developed by Baar et al. and published in Cell in 2017, representing one of the most influential papers in the cellular senescence field. FOXO4-DRI stands for: **FOXO4** (the target transcription factor) + **D** (D-amino acid configuration) + **RI** (retro-inverso — reversed sequence). The D-retro-inverso strategy produces a mirror-image peptide that mimics the three-dimensional shape of the parent L-amino acid peptide but is highly resistant to proteolytic degradation. As a research compound, FOXO4-DRI has no approved indication, no human clinical trial data, and no established human dosing. It is sold by research peptide vendors as a lyophilized compound for preclinical investigation.

GHK-Cu (glycyl-L-histidyl-L-lysine:copper(II)) is a naturally occurring copper-binding tripeptide first identified in human plasma in 1973 by Loren Pickart. It consists of three amino acids — glycine, histidine, and lysine — complexed with a copper(II) ion at a 1:1 ratio. The peptide is found in plasma, saliva, and urine, with circulating levels that decline significantly with age: from approximately 200 ng/mL at age 20 to roughly 80 ng/mL by age 60. GHK-Cu has attracted research interest for its unusually broad biological activity profile relative to its small size. It modulates the expression of over 4,000 human genes, representing roughly 6% of the genome, with a net effect that shifts gene expression patterns toward tissue repair, anti-inflammatory, and antioxidant states. It is commercially available in cosmetic formulations and remains under investigation for wound healing, tissue remodeling, and anti-aging applications.

Livagen is a synthetic tetrapeptide Lys-Glu-Asp-Ala (KEDA), developed as a liver and immune bioregulator by the Khavinson group at the St. Petersburg Institute of Bioregulation and Gerontology. Despite its classification as a "liver" bioregulator based on its origin from bovine liver tissue extract, the published evidence for Livagen focuses primarily on its effects on chromatin structure in lymphocytes — positioning it more accurately as an immune/epigenetic aging compound.

Melanotan I (afamelanotide, brand name Scenesse) is a synthetic analog of alpha-melanocyte-stimulating hormone (α-MSH), an endogenous peptide that regulates skin pigmentation and photoprotection. It is the first melanocortin peptide to receive regulatory approval: the European Medicines Agency (EMA) approved it in 2014, and the FDA approved it in October 2019 for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP). EPP is a rare inherited metabolic disorder caused by mutations in the ferrochelatase (FECH) gene, resulting in accumulation of protoporphyrin IX in red blood cells, plasma, and skin. Exposure to visible light triggers a severe, painful phototoxic reaction in affected individuals, restricting sun exposure and severely limiting quality of life. Afamelanotide addresses this by constitutively inducing eumelanin production independent of UV exposure, raising the photosensitivity threshold. Melanotan I is structurally distinct from Melanotan II (PT-141 analog) and has a different receptor profile and approved indication. The two should not be confused.

SNAP-8 (acetyl octapeptide-3, INCI name: Acetyl Octapeptide-3) is a synthetic cosmetic peptide developed by Lipotec as an extension of Argireline (acetyl hexapeptide-3). It is an 8-amino acid peptide with an N-terminal acetyl group and C-terminal amide, designed to competitively inhibit SNAP-25, a SNARE complex protein essential for neurotransmitter vesicle fusion at the neuromuscular junction. The proposed result is partial reduction of muscle contraction amplitude, attenuating dynamic wrinkle formation. SNAP-8 is a cosmetic ingredient — not a pharmaceutical drug. It is not subject to clinical trial requirements or drug approval pathways. All efficacy data in circulation comes from manufacturer-sponsored studies (Lipotec), which are not independently peer-reviewed clinical trials. No independent RCT for SNAP-8 has been published in the medical literature.

SS-31 (elamipretide, formerly Bendavia/MTP-131) is a synthetic tetrapeptide that selectively targets the inner mitochondrial membrane. Developed by Hazel Szeto at Weill Cornell Medical College, it is the lead compound in a class of mitochondria-targeted peptides (Szeto-Schiller peptides) designed to restore mitochondrial function in aging and disease. The peptide carries a 3+ charge at physiological pH due to its D-arginine and lysine residues, which drives its rapid, energy-independent accumulation in mitochondria at concentrations 1,000-5,000 fold greater than in the cytoplasm. Elamipretide is in clinical development by Stealth BioTherapeutics for several mitochondrial diseases, including Barth syndrome, primary mitochondrial myopathy, and age-related macular degeneration. It represents a fundamentally different approach to antioxidant therapy — rather than scavenging reactive oxygen species after they form, SS-31 optimizes mitochondrial electron transport to prevent excessive ROS generation at the source. This mechanism has generated interest in the anti-aging research community, as mitochondrial dysfunction is a hallmark of cellular aging.

Testagen is a synthetic tetrapeptide Lys-Glu-Asp-Gly (KEDG), developed as a testicular/gonadal tissue bioregulator by the Khavinson group at the St. Petersburg Institute of Bioregulation and Gerontology. It is derived from bovine testicular tissue and proposed to modulate testosterone biosynthesis and Leydig cell function through epigenetic mechanisms. **Important nomenclature note:** Testagen (KEDG) should not be confused with Vesugen (KED). Vesugen is the Lys-Glu-Asp **tripeptide** (3 amino acids). Testagen is the Lys-Glu-Asp-**Gly tetrapeptide** (4 amino acids, with Gly added at the C-terminus). These are distinct compounds despite overlapping names in some vendor catalogs. **Evidence status:** Testagen has no confirmed peer-reviewed publications with a PubMed-indexed PMID for standalone characterization. It is referenced within Khavinson's comprehensive bioregulator review articles but lacks the primary animal study data that other Khavinson tetrapeptides (Pancragen, Vesugen, Livagen) have published. It represents the thinnest evidence base in the vendor-sold Khavinson peptide series.

Vesugen is a synthetic tripeptide Lys-Glu-Asp (KED), developed as a vascular endothelial bioregulator by the Khavinson group at the St. Petersburg Institute of Bioregulation and Gerontology. It is proposed to restore age-related decline in endothelial cell proliferative capacity through epigenetic mechanisms, specifically by binding the promoter region of the Ki-67 (MKI67) gene to upregulate endothelial cell division programs. Note on nomenclature: Vesugen is the KED tripeptide (Lys-Glu-Asp). It should not be confused with Testagen, which is the KEDG tetrapeptide (Lys-Glu-Asp-Gly — an additional Gly residue). These are distinct compounds with different vendor designations. Some listings conflate the two.

Vilon is the Lys-Glu (KE) dipeptide — the shortest synthetic peptide bioregulator in the Khavinson bioregulator series. It is one of three active fractions isolated from Thymalin (the heterogeneous calf thymus extract), alongside Crystagen (EDP) and Thymogen (EW). As the dipeptide fraction, Vilon represents the minimal pharmacophore of thymic peptide activity: two amino acids that retain measurable biological effects in cell and animal models. Vilon has a published animal lifespan extension study (PMID 10944717) — one of the few Khavinson bioregulators with this type of longitudinal outcome data. In CBA female mice, Vilon inhibited spontaneous tumor growth and extended mean lifespan compared to untreated controls.