3AA Preclinical
Cartalax
Synthetic cartilage tripeptide (Ala-Glu-Asp) from the Khavinson school that activates SOX9/collagen-II/aggrecan expression in aging mesenchymal stem cells, suppresses MMP-9, and inhibits chondrocyte apoptosis in preclinical models.
In Plain English:
Cartalax is a three-amino-acid chain — alanine, glutamic acid, and aspartic acid — synthesised as the minimal bioactive sequence isolated from bovine cartilage tissue by Professor Vladimir Khavinson at the St. Petersburg Institute of Bioregulation and Gerontology. The sequence Ala-Glu-Asp appears in the alpha-1 chain of type XI collagen, a structural protein critical to cartilage integrity, and is proposed to act as a tissue-specific epigenetic signal: entering chondrocyte nuclei, binding histone and DNA promoter sites, and resetting gene expression patterns that drift toward degradation and apoptosis with age. In cell culture studies on aging human mesenchymal stem cells (MSCs), AED at 200 ng/mL activated gene expression and protein synthesis of four key chondrogenic markers — SOX9, aggrecan (ACAN), type II collagen (COL2A1), and cartilage oligomeric matrix protein (COMP) — at a tenfold lower concentration than the parent cartilage polypeptide complex required for the same effect. In skin fibroblast aging models, AED and its AEDG sibling (Epitalon) were the only peptides in a four-compound panel to suppress caspase-3-dependent apoptosis while also upregulating Ki-67 (proliferation) and CD98hc (regeneration) and inhibiting MMP-9 (matrix degradation). In MSC longevity gene expression studies, AED enhanced IGF1 gene expression 3.5–5.6-fold in two independent aging models and stimulated NFκB. No randomised controlled trials in humans have been published; all evidence is preclinical, originates from the Khavinson institute network, and has not been independently replicated by Western research groups. The commercial capsule form (Cytogen AC-4, 60 capsules × 0.2 g) classifies as a food supplement. Research-grade lyophilised powder is sold by Western peptide vendors for in vitro use.
Research Maturity
Preclinical (~8-12 peer-reviewed papers (2012-2023), mostly in vitro/in silico; no RCTs or independent replication+ Studies)
Focus
Cartilage Support
Joint Health
Origin
Identified and synthesised by Vladimir Kh. Khavinson and colleagues at the St. Petersburg Institute of Bioregulation and Gerontology (Russia) as part of the 'cytogen' directed-synthesis programme. The parent extract is a cartilage polypeptide complex (AC-4 / CPC) derived from bovine cartilage tissue; compositional analysis identified alanine, glutamic acid, and aspartic acid as the dominant regulatory amino acid motif, corresponding to a conserved segment of the alpha-1(XI) collagen chain. The commercial formulation is sold as Cartalax® by the institute-affiliated brand (Cytogens AC-4). First described alongside Chondroxide-type bioregulators in the Khavinson geroprotection programme in the 1990s; the synthesised tripeptide form entered the directed-cytogen catalogue in the 2000s. Research-grade lyophilised AED appeared on Western vendor catalogues from approximately 2018 onward.
Mechanism
Proposed to act through direct nuclear penetration and DNA/histone binding — consistent with the class mechanism characterised for ultrashort Khavinson peptides (PMID 34834147), where 2–7 amino acid peptides are modelled to bind N-terminal histone motifs and GC-rich DNA promoter sequences, resetting organ-specific transcription programmes. For AED specifically: (1) LAT1 (large neutral amino acid transporter 1) is identified by ICM-Pro molecular modelling as the likely transmembrane carrier (ICM-Score −26.65; PMC9323678), enabling intracellular access despite the peptide's slight negative charge; (2) activates SOX9 gene expression and protein synthesis in aging human MSCs — SOX9 is the master transcription factor for chondrogenic commitment (PMID 37176122, PMID 37782646); (3) upregulates aggrecan (ACAN) and type II collagen (COL2A1) gene expression and protein levels at 200 ng/mL in replicatively aged MSCs (PMID 37782646); (4) upregulates COMP (cartilage oligomeric matrix protein) in MSC aging models (PMID 37782646); (5) enhances IGF1 gene expression 3.5–5.6-fold in passage-based and stationary MSC aging models — IGF1 is a principal chondrocyte survival and anabolic signal (PMID 32399807); (6) stimulates NFκB gene expression in both MSC aging models (PMID 32399807); (7) suppresses Ki-67-negative, caspase-3-positive apoptotic phenotype in aging skin fibroblasts — a surrogate for chondrocyte ageing — while simultaneously upregulating Ki-67 (proliferation) and CD98hc (CD98 heavy chain, membrane amino acid transporter/regeneration marker) (PMID 27259496); (8) inhibits MMP-9 synthesis, an enzyme responsible for extracellular matrix collagen degradation that increases with cellular aging (PMID 27259496); (9) reduces p53 expression in chondrocyte culture models, interpreted as suppression of the apoptosis programme; (10) upregulates PCNA (proliferating cell nuclear antigen) in cartilage tissue cultures. Effects are observed at nanomolar to low microgram concentrations, consistent with epigenetic rather than pharmacological-receptor agonist mechanisms.
Outcome
SOX9 gene expression and protein synthesis in aging human MSCs (PMID 37782646, activated at 200 ng/mL); aggrecan (ACAN) gene expression and protein in aging MSCs (PMID 37782646); type II collagen (COL2A1) gene expression and protein in aging MSCs (PMID 37782646); COMP gene expression and protein in aging MSCs (PMID 37782646); IGF1 gene expression in MSC aging culture — 3.5–5.6-fold increase (PMID 32399807); NFκB gene expression in MSC aging culture — stimulated (PMID 32399807); Ki-67 proliferation marker in aging fibroblasts — increased (PMID 27259496); CD98hc glycoprotein — increased (PMID 27259496); caspase-3 expression — suppressed, indicating apoptosis inhibition (PMID 27259496); MMP-9 synthesis — inhibited (PMID 27259496); p53 expression in chondrocyte models — reduced; PCNA in cartilage tissue culture — increased; cartilage area index in rat tissue cultures (young and aged animals) — reported 18–38% increase versus untreated controls.
