OBJECTIVE: Following previous clinical trials, an antiaging product (Restorative Skin complex [RSC]; Alastin Skin Care Carlsbad, a Galderma company), was investigated for its effects on Klotho gene regulation, telomere length, and histological biopsy changes to provide a comprehensive picture of the mechanism and efficacy of its anti-aging effect. METHODS: Neonatal human fibroblasts were used for telomere length studies to examine the effect of the full RSC formulation and the amino acid components Tripeptide-1 and Hexapeptide-12 (TriHex™) on these cellular aging mechanisms. In addition, RNA sequencing was conducted using human keratinocytes specifically investigating Klotho and related genes. This was supplemented by a clinical study using biopsy samples. RESULTS: TriHex™ significantly upregulated the Klotho gene and related FGF23, FGFR1 and FOXO3B anti-aging genes. Significant telomere shortening reduction over control was demonstrated with the RSC formulation at four weeks and with TriHex™ at six weeks for all percentiles tested. Previous clinical studies demonstrated that the use of the antiaging regimen for 12 weeks produced a statistically significant improvement in scores for all evaluated parameters. Restaining of previous biopsy blocks from the clinical trial revealed positive ECM changes, stimulation of collagen, fibrillin, CD44 and elastin. LIMITATIONS: The study was limited by a relatively small numbers of patients in the clinical trial and the non-competitive nature of the trial. CONCLUSION: RSC anti-aging formulation and its TriHex™ components demonstrated significant reduction in telomere shortening, upregulation of Klotho and FOXO3 genes and biopsy validation of antiaging efficacy. This new science supplements previous trials that demonstrated clinical efficacy of the formulation