Epithalon
A synthetic tetrapeptide (Ala-Glu-Asp-Gly) based on epithalamin, a natural extract from the pineal gland. Studied primarily for its ability to activate telomerase, the enzyme that maintains telomere length at chromosome ends. Telomere shortening is a fundamental mechanism of cellular aging, making Epitalon one of the most discussed peptides in anti-aging research. Originally developed by Dr. Vladimir Khavinson in Russia.
Typical Dosage
Standard: 5-10 mg subcutaneous once daily for 10-20 days. Cycled two or three times per year. Some protocols use 10 days on, followed by a 4-6 month break before repeating.
Administration
Subcutaneous or intravenous injection
Mechanism of Action
Epithalon (also spelled Epitalon) is a synthetic tetrapeptide (Ala-Glu-Asp-Gly) based on epithalamin, a peptide extract from the pineal gland first studied by Professor Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology. Its primary reported mechanism is the activation of telomerase — the ribonucleoprotein enzyme complex responsible for maintaining telomere length at chromosome ends.
Telomeres are repetitive nucleotide sequences (TTAGGG in humans) that cap and protect chromosome ends from degradation, fusion, and recognition as DNA damage. With each cell division, the DNA replication machinery cannot fully copy the very end of the lagging strand (the 'end replication problem'), resulting in progressive telomere shortening. When telomeres reach a critical length, cells enter replicative senescence (permanent growth arrest) or apoptosis — a fundamental mechanism of cellular aging. Telomerase, composed of the catalytic subunit hTERT (human telomerase reverse transcriptase) and the RNA template component hTR/TERC, can add TTAGGG repeats back to chromosome ends, counteracting this shortening.
Epithalon reportedly activates the expression of the hTERT gene, increasing telomerase activity in somatic cells. In cell culture studies, epithalon treatment was associated with increased telomere length and extended replicative lifespan in human fibroblasts and retinal pigment epithelial cells. The peptide also reportedly stimulates melatonin production by the pineal gland, potentially through gene-regulatory effects on pineal cells. Melatonin itself is a potent antioxidant and circadian regulator, and its decline with age correlates with numerous age-related changes. Additional reported effects include normalization of T-cell function, modulation of neuroendocrine signaling, and improved antioxidant enzyme expression. It should be noted that the majority of published research comes from Russian institutions, and large-scale, peer-reviewed Western clinical trials are lacking.
Regulatory Status
Not FDA approved. Research from St. Petersburg Institute of Bioregulation and Gerontology (Russia). Available through research peptide suppliers.
Risks & Safety
Common: injection site irritation, mild headache, transient drowsiness. Serious: theoretical concern about telomerase activation in pre-cancerous or cancerous cells (telomerase is overexpressed in most cancers), limited Western clinical data (most studies are from Russian institutions). Rare: allergic reactions. Generally reported as well tolerated in available studies. Long-term effects of periodic telomerase activation are not fully understood. Not FDA approved.
Research Papers
2Published: December 31, 2025
Abstract
Therapeutic peptides are emerging as promising adjuncts in the management of orthopaedic injuries, grounded in their ability to modulate molecular signaling networks central to cellular medicine. By acting on key pathways such as PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK, peptides exert influence over tissue regeneration, inflammation resolution, and neuromuscular recovery. Wound-healing peptides such as BPC-157, TB-500, and GHK-Cu promote angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, whereas growth hormone secretagogues like ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 activate IGF-1 signaling and satellite cell repair. Recovery-enhancing agents such as epithalon, delta sleep-inducing peptide, and pinealon target circadian and mitochondrial regulators, and neuroactive peptides like selank, semax, and dihexa enhance brain-derived neurotrophic factor and HGF/c-Met pathways critical to neuroplasticity. Although preclinical studies are promising, there is a current lack of clinical trials. This review integrates current mechanistic insights with orthopaedic relevance, emphasizing safety, efficacy, and future directions for responsible integration into musculoskeletal care.
Published: March 16, 2025
Abstract
Epitalon, also known as Epithalon or Epithalone, is a tetrapeptide, Ala-Glu-Asp-Gly (AEDG), which was synthesized based on the amino acids composition of Epithalamin, a bovine pineal gland extract, prior to its discovery in pineal gland polypeptide complex solution. During the last 25 years, this compound has been extensively studied using in vitro, in vivo, and in silico methods. The results of these studies indicate significant geroprotective and neuroendocrine effects of Epitalone, resulting from its antioxidant, neuro-protective, and antimutagenic effects, originating from both specific and nonspecific mechanisms. Although it has been demonstrated that Epitalon exerts, among other effects, a direct influence on melatonin synthesis, alters the mRNA levels of interleukin-2, modulates the mitogenic activity of murine thymocytes, and enhances the activity of various enzymes, including AChE, BuChE, and telomerase, it remains uncertain whether these are the sole mechanisms of action of this compound. Moreover, despite the considerable volume of research on the biological and pharmacodynamic characteristics of Epitalon, the quantity of physico-chemical and structural investigations of this peptide remains quite limited. This review aims to conclude the most important findings from such studies, thus presenting the current state of knowledge on Epitalon.
Related Peptides
AEDG Peptide
A tetrapeptide (Ala-Glu-Asp-Gly) identical to Epithalon's core active sequence — effectively the same compound. Studied for telomerase activation and pineal gland regulation, promoting melatonin production and potentially slowing cellular aging through telomere maintenance. Part of the Khavinson bioregulator peptide family developed at the Institute of Bioregulation and Gerontology in St. Petersburg.
CJC-1295 (no DAC)
A synthetic GHRH analogue (also called Mod GRF 1-29) consisting of the first 29 amino acids of native GHRH with four amino acid substitutions for increased enzymatic stability. Stimulates natural, pulsatile growth hormone release while preserving the body's somatostatin feedback regulation. One of the most commonly prescribed GH peptides, often combined with Ipamorelin for synergistic effects.
CJC-1295 + Ipamorelin
The most commonly prescribed peptide combination in anti-aging and regenerative medicine. Pairs the GHRH analogue CJC-1295 (Mod GRF 1-29) with the selective ghrelin-mimetic Ipamorelin for synergistic, pulsatile growth hormone release. Exploits two complementary signaling pathways — cAMP (GHRH) and calcium/PLC (ghrelin receptor) — to amplify GH pulses while maintaining minimal side effects.
CJC-1295 with DAC
CJC-1295 with Drug Affinity Complex — the same core GHRH analogue as Mod GRF 1-29 but with a reactive succinimide linker that covalently binds to circulating albumin after injection. This albumin binding dramatically extends the half-life from 30 minutes to nearly a week, allowing weekly dosing. Produces sustained rather than pulsatile GH elevation, which some practitioners consider less physiological.