Patricia Farris, MD, on AP31’s Anti-Aging Power

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In a recent conversation with Dermatology Times, Patricia Farris, MD, elaborated on research recently published in the Journal of Drugs in Dermatology. The study, titled, “Acetyl Dipeptide-31 Amide: A Novel Cosmetic Anti-Inflammatory Peptide That Demonstrates Anti-Aging, Firming, and Lifting Benefits,” explores the potential of AP31, a micropeptide designed to address both aging and inflammation in the skin.

The study is a response to the growing demand for safe and effective cosmetic ingredients capable of treating common signs of aging, such as fine lines, wrinkles, sagging, and discoloration. Unlike most cosmeceutical peptides, AP31 stands out for its dual benefits as an anti-inflammatory and anti-aging agent while maintaining a small molecular size.

Over a 16-week clinical evaluation, AP31 demonstrated significant positive results, including improved skin firmness, reduced inflammation markers, and enhanced facial contouring, all while being well-tolerated by participants.

Farris, a board-certified dermatologist with over 35 years of experience in research, aesthetics, and clinical dermatology, shed light on the innovative methods used in this study, the science behind AP31, and its implications for both patients and healthcare professionals.

Q&A

Q: How does AP31 compare to other anti-aging treatments?

A: Although there seems to be an endless stream of anti-aging products entering the marketplace, very few offer something that is truly novel. This paper chronicles the 8-year research and development of acetyl dipeptide31-amide (AP31), a low molecular weight cosmetic peptide. The goal was to develop a peptide that would provide multimodal skin benefits. AP31 is only 229.3 D, far below the 500 D threshold required for skin penetration. In addition, the chemical structure and pH were optimized and a niosomal carrier added to further enhance skin penetration. Studies on human cadaveric skin confirm excellent skin penetration for cream, lotion, and water in silicone preparations of AP31. So, while cosmetic peptides are known to be difficult to deliver to the skin, this dipeptide was synthesized, engineered and formulated to maximize bioavailability.

Q: What are the most significant improvements from the study? 

A: This paper outlines a series of studies that were conducted to confirm the biologic activity of AP31. Pre-clinical, in vitro studies, demonstrate that AP31mitigates the release of inflammatory mediators including IL-4, IL-6, IL-8, IL-17 and tumor necrosis factor alpha (TNF-α)when compared to dexamethasone and tacrolimus. These inflammatory mediators play a role in skin disorders such as eczema and contribute to aging via the inflammaging pathway. In vitro studies also show that AP31 enhances expression of 5 extracellular matrix components including pro-collagen, elastin, decorin, fibronectin and hyaluronic acidin cultured fibroblasts. Ex vivo studies confirm that application of an AP31cream to human skin explants significantly increased collagen III and elastin compared to untreated control.Thus, by modulating important extracellular matrix components, AP31improves the biomechanical and viscoelastic properties of aging skin, restoring them to a more youthful state.

Gene analysis in full thickness human skin equivalents treated with AP31 revealed a positive effect on many genes including those involved with barrier function, skin hydration, skin plumping, and epidermal metabolism. There was also a downregulation of genes involved in cellular senescence. AP31 upregulated 7 pathways previously shown to be downregulated in aging skin and downregulated 4 pathways known to be upregulated in skin aging.

A 16-week, prospective, single arm, single center clinical study was conducted of 38 women aged 45 to 60 with Fitzpatrick Skin Types I-IV. Subjects had mild to moderate jawline sagging, mild to moderate wrinkles, and moderate fine lines according to the Griffiths scale at baseline, and no cosmetic treatment or procedures from a physician or skincare professional for 6 months prior to initiating the study. After 16 weeks of use, a test formulation containing AP31 0.4%, a low concentration glycolic acid, gluconolactone and acetyl tyrosinamide produced significant improvements in the lower face including jawline sagging, appearance of nasolabial folds, and global lift. These lifting benefits are unusual for a topical formulation and can be explained by volume boosting benefits of AP31. Other attributes of skin aging were also significantly improved including fine lines and wrinkles, skin tone, and smoothness. There was no tolerability issues noted, and subject self-assessment data with consistent with investigator grading.

Q: What do the results mean for patients and clinicians?

A: This data confirms that AP31 is a novel, gentle, effective multi-modal anti-aging ingredient with firming, lifting, and facial contouring benefits. Dermatologists and their patients can find AP31 in several over-the-counter cosmeceuticals marketed to rejuvenate aging skin. 

Q: What are the next steps in research?

A: Studies have just been completed to evaluate the effects of AP31 across diverse skin types and age ranges. The ECM boosting benefits of AP31 suggest that it may be helpful in patients with early signs of collagen decline and offer a cosmetic solution for younger patients with the clinical findings associated with pre-aging. 

References

1. Edison BL, Parsa R, Dufort M, et al. Acetyl dipeptide-31 amide: A novel cosmetic anti-inflammatory peptide that demonstrates anti-aging, firming, and lifting benefits. J Drugs Dermatol. 2025;24(1):23-33. doi:10.36849/JDD.8786