Topical Peptides: Skin Aging Research 

Studies suggest that many physiological systems, including defense, immunity, stress, growth, homeostasis, and reproduction, may rely on peptides for signaling or regulation. Short, stable, synthetic peptides for use in extracellular matrix production, pigmentation, innate immunity, and inflammation have been developed using these principles for application in dermatological research.

Peptides have come a long way since the discovery of penicillin. Research suggests topical peptides may potentially modulate neurotransmitter activity, extracellular matrix component signaling, and peptide transport. Scientists speculate that peptides may be attractive research candidates because they may be involved in various skin-related physiological processes, may act selectively, and do not appear to be immunogenic.

What are Peptides?

Peptides are chains of amino acids joined together by peptide bonds. Peptides are a chemical intermediate between simpler small molecule compounds and more complicated proteins. Studies suggest that natural peptides may involve many biological processes, from defense and immunity to stress, growth, homeostasis, and reproduction. They are best recognized for their signaling/regulatory potential in these areas. Scientists have recently created short, stable, and synthetic peptides hypothesized to play a role in extracellular matrix production, pigmentation, innate immunity, and inflammation.

Studies on Topical Peptides

Modulation of signaling by proteins of the extracellular matrix Collagen, fibronectin, elastin, and laminin are all proteins found in the skin’s extracellular matrix. Still, the production of these proteins reduces over time, and they break down faster. In addition to its structural role, the extracellular matrix regulates cellular activities, including proliferation and differentiation. Small peptides (matrikines) produced by the proteolytic breakdown of extracellular matrix proteins are hypothesized to mediate these actions. Matrikines are signaling proteins that mediate communication between cell-wall receptors and matrix components.

Topical Peptides and Collagen

Topical Peptides Skin Aging Research 

Research suggests that peptides may have a role in aging by altering collagen homeostasis. The oligopeptide pentapeptide-3 (Lys-Thr-Thr-Lys-Ser, KTTKS) was among the first to be researched for its potential in this regard. It is a portion of the propeptide found at the carboxyl terminus of type I collagen. The findings of a study implied this peptide fragment seemed to improve the fibroblasts’ ability to generate extracellular matrix. In addition, it is purported to increase the production of collagen types I and III and fibronectin in a concentration- and time-dependent way without affecting total protein synthesis or the ratio of secreted proteins to cell-associated proteins. Osborne et al. conducted an experiment including 180 research models and suggested that compared to controls, pal-KTTKS appeared to dramatically reduce bumpy texture and fine wrinkles.

Scientists speculate that palmitic acid may be conjugated with tripeptide-1 (glycyl-l-histidyl-l-lysine) to create pal-tripeptide-1. Studies in vitro have suggested that this mixture may increase collagen and glycosaminoglycan production.

Matrix metalloproteinases, a family of metal-dependent endopeptidases, primarily catalyze the degradation of extracellular matrix components. Matrix metalloproteinases become more active with age. As suggested by enzyme studies, the excessive degradation of the dermal matrix that occurs with photoaging and chronological aging may be mitigated by tripeptide-2. In addition to dysfunctional telomeres, senescence may be triggered by the reduction in progerin synthesis caused by trifluorotripeptide-2, studies suggest. Therefore, this peptide is hypothesized to supplement age-related cellular processes.

Thrombospondin is a natural signal peptide that is mimicked by the synthetic signal peptide palmitoyl tripeptide-5 (palmitoyl-lysyl-valyl-lysine), which is speculated to bind to the inactive form of transforming growth factor- and potentially trigger the release of active transforming growth factor. Creams containing 2.5% palmitoyl tripeptide-5, 10% palmitoyl pentapeptide-3, or placebo were applied twice daily for 84 days to 60 research models in a randomized controlled experiment. The findings purported the average and maximum parameters for pain alleviation appeared considerably reduced by 12% when palmitoyl tripeptide-5 was used.

Topical Peptides and Elastin Modulation

Microfibrils and matrix elastin make up elastic fibers, an essential part of the extracellular matrix. Age and excessive exposure to UV radiation bring degenerative alterations in the elastin fiber meshwork.

The hexapeptide Val-Gly-Val-Ala-Pro-Gly is a structural motif found in elastin molecules in mammals, including bovines and pigs. Scientists propose the production of elastin may be negatively regulated by this peptide, which seems to display a high degree of selectivity for these molecules. Investigations purport it may also promote angiogenesis and endothelial cell migration in skin fibroblasts. Products containing palmitoyl oligopeptide, which includes this elastin fragment, have been hypothesized to promote “reconstruction of the dermis” and induce “chemotaxis for restructuring and repair.”

Topical Peptides and Melanin

Melanin serves as an antioxidant and a shield for nuclear DNA from the damaging effects of sunlight. Research suggests that Tyrosinase may be activated during melanin formation when the melanocyte-stimulating hormone binds to the melanocortin-1 receptor. Topical substances containing various analogs of -melanocyte-stimulating hormones have been researched for photoprotection and avoiding photocarcinogenesis. Findings of recent research suggested that two of these peptides, a tetrapeptide (His-D-Phe-Arg-Trp) and a tripeptide (His-D-Phe-Arg), seemed more effective than -melanocyte-stimulating hormone at promoting melanogenesis, suppressing apoptosis, and H2O2 production, and facilitating the repair of DNA damage in melanocytes that have been exposed to UV light.

Buy topical peptides if you are a scientist interested in further studying these research compounds.


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[iii] Zhang L, Falla TJ. Cosmeceuticals and peptides. Clin Dermatol 2009;27:485-94.

[iv] López-Otín C, Matrisian LM. Emerging roles of proteases in tumor suppression. Nat Rev Cancer 2007;7:800-8.

[v] Bruno BJ, Miller GD, Lim CS. Basics and recent advances in peptide and protein drug delivery. Ther Deliv 2013;4:1443-67.

[vi] Kligman AM. Cosmetics. A dermatologist looks to the future: Promises and problems. Dermatol Clin 2000;18:699-709.

[vii] Peptide Therapeutics Market (by Applications, by Route of Administration, and by Marketing Status) – Global Industry Analysis, Size, Share, Growth, Trends and Forecast 2014-2020; April, 2015.

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