Acetyl Dipeptide-31 Amide: A Novel Cosmetic Anti-Inflammatory Peptide That Demonstrates Anti-Aging, Firming, and Lifting Benefits

BACKGROUND: There is continuous demand for safe, effective cosmetic ingredients to treat the signs of aging skin, including fine lines, wrinkles, brown spots, discoloration, laxity, and sagging. While there are a plethora of cosmeceutical peptides, few combine anti-aging and anti-inflammatory benefits with small size. METHODS: Preclinical and clinical studies evaluated the anti-inflammatory properties, anti-aging benefits, and tolerability of acetyl dipeptide-31 amide (AP31), a novel, small, anti-aging micropeptide, to understand its impact as a multifaceted, cosmetic, anti-aging, and anti-inflammaging ingredient. RESULTS: In vitro, AP31 statistically significantly reduced the release of inflammatory mediators interleukin (IL)-4, IL-6, IL-8, IL-17, and tumor necrosis factor alpha, and statistically significantly increased levels of dermal extracellular matrix components, ie, procollagen, elastin, decorin, fibronectin, and hyaluronic acid (all P<0.05 vs vehicle controls). Statistically significant increases in extracellular matrix biomarker levels were also seen in AP31-treated human skin explants (8 days). In human skin equivalents, AP31 favorably influenced cellular pathways known to contribute to skin aging. AP31 positively impacted genes involved in barrier function, skin hydration, skin plumping, and epidermal metabolism. Clinical evaluations of a finished product over 16 weeks demonstrated improvements in jawline sagging, global lift, nasolabial fold appearance, fine lines and wrinkles, smoothness, skin tone, and hyperpigmentation. Subject self-assessment of efficacy was consistent with the clinical grading. No statistically significant changes from baseline in tolerability assessments of edema, erythema, dryness, burning, stinging, itching, or tightness were reported. CONCLUSIONS: AP31 is a novel, multifunctional, non-irritating, cosmeceutical micropeptide that improves clinical signs of aging, lifts and contours facial skin, and reduces inflammation markers. J Drugs Dermatol. 2025;24(1):23-33. doi:10.36849/JDD.8786.