Function of trifluoroacetyl tripeptide-2 in human skin


Trifluoroacetyl tripeptide-2 (TFA-T2) is an innovative peptide compound that has garnered significant attention in dermatological and cosmetic research. Known for its unique structural modification, which includes the addition of a trifluoroacetyl group, TFA-T2 enhances skin's resilience and mitigates the effects of aging.

What is trifluoroacetyl tripeptide-2?

Trifluoroacetyl tripeptide-2 (sequence: TFA-Val-Try-Val-OH) is a synthetic peptide designed as a matrix metalloproteinase and an elastase inhibitor, consisting of three amino acids modified with a trifluoroacetyl group. This modification confers increased stability and enhances the peptide's bioavailability. The trifluoroacetyl group, being highly electronegative, improves the peptide's interaction with skin receptors and cellular components, thereby potentiating its biological activity. The in vitro studies were conducted to assess the effects of trifluoroacetyl-tripeptide-2 (TT2) on ECM protection, on the synthesis of proteoglycans in cell-matrix interactions, and on the synthesis of progerin in mature human normal fibroblasts, a protein identified as a co-inducer of cellular senescence. The results show that trifluoroacetyl-tripeptide-2 has the broader anti-aging properties. It can decrease progerin synthesis, increase proteoglycan production and contract collagens, therefore it can reduce wrinkles and increase firmness of the tissue. In addition, it was evaluated in two in vitro split face studies about its anti-wrinkle, anti-sagging and skin firmness effects. According to the studies, trifluoroacetyl-tripeptide-2 has progressive effects on wrinkles, firmness, elasticity and sagging.

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Trifluoroacetyl tripeptide-2 mechanisms of action

Modulation of extracellular matrix (ECM) components

The extracellular matrix (ECM) is critical for maintaining skin structure and function. TFA-T2 influences ECM dynamics by modulating both the synthesis and degradation of its components. A key aspect of TFA-T2's action is its regulation of matrix metalloproteinases (MMPs), enzymes that degrade collagen and other ECM proteins. Specifically, TFA-T2 downregulates MMP-1, an enzyme responsible for collagen breakdown, thereby preserving collagen integrity. Simultaneously, TFA-T2 stimulates the production of collagen and elastin by upregulating genes such as COL1A1 and ELN. This dual action—reducing collagen degradation while enhancing its synthesis—helps maintain a robust and resilient dermal matrix, crucial for youthful and firm skin.

Enhancement of cellular communication

Effective intercellular communication is essential for skin homeostasis and repair. TFA-T2 influences several signaling pathways that are pivotal for cellular interactions and skin health. One such pathway is the Transforming Growth Factor-beta (TGF-β) pathway, which is instrumental in regulating ECM production and wound healing. TFA-T2 enhances TGF-β signaling, promoting fibroblast activity and boosting collagen production. Moreover, TFA-T2 affects the expression of microRNAs (miRNAs) involved in skin aging. For instance, it can downregulate miR-29, a microRNA that inhibits collagen synthesis. By modulating these regulatory RNAs, TFA-T2 fosters an environment conducive to ECM maintenance and skin rejuvenation.

Antioxidant activity

Oxidative stress, primarily caused by reactive oxygen species (ROS), is a major factor in skin aging. TFA-T2 exhibits significant antioxidant properties, counteracting oxidative damage. It enhances the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase, which neutralize ROS. Additionally, TFA-T2 activates the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a critical regulator of antioxidant defense mechanisms. This activation leads to the upregulation of various antioxidant proteins, providing comprehensive protection against oxidative stress.

What does trifluoroacetyl tripeptide-2 do for the skin?

As a cosmetic ingredient, trifluoroacetyl-tripeptide-2 has excellent emulsifying, dispersing, antistatic, smearing and wetting ability. It can avoid the damage of residual substances to the skin's natural protective layer. Therefore, trifluoroacetyl-tripeptide-2 is important for controlling the phenomenon of aging.

Improvement of skin elasticity and firmness

One of the most notable benefits of trifluoroacetyl tripeptide-2 (TFA-T2) is its capacity to enhance skin elasticity and firmness. This improvement is primarily due to its dual action on the extracellular matrix (ECM). TFA-T2 downregulates matrix metalloproteinases (MMPs), particularly MMP-1, which are enzymes responsible for the degradation of collagen. By inhibiting these enzymes, TFA-T2 reduces collagen breakdown, preserving the structural integrity of the dermal matrix. Simultaneously, TFA-T2 upregulates the production of collagen and elastin by stimulating the expression of genes like COL1A1 and ELN. This increase in collagen and elastin synthesis contributes to a denser and more elastic dermal layer, which manifests as firmer and more resilient skin. This dual mechanism not only helps in maintaining the skin's structural framework but also reduces visible signs of sagging and loss of firmness that are commonly associated with aging.

Promotion of skin regeneration

TFA-T2 plays a crucial role in promoting skin regeneration by enhancing the activity and proliferation of dermal fibroblasts. Fibroblasts are vital for the production and maintenance of ECM components. By stimulating these cells, TFA-T2 boosts the synthesis of collagen, elastin, and other essential proteins, which are necessary for skin repair and regeneration. This increased fibroblast activity accelerates the skin's natural healing processes, aiding in the repair of damaged tissues and the renewal of the skin's structural components. The result is an overall improvement in skin texture and appearance, with a more youthful and regenerated skin surface.

Reduction of inflammation

Chronic inflammation is a significant contributor to skin aging and various dermatological conditions. TFA-T2 has demonstrated anti-inflammatory properties, which help mitigate the inflammatory responses in the skin. It achieves this by downregulating the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). By reducing these inflammatory markers, TFA-T2 helps prevent the chronic inflammation that can lead to accelerated aging and the exacerbation of skin conditions like acne, rosacea, and eczema. This anti-inflammatory effect is crucial for maintaining a calm and balanced skin environment, promoting overall skin health and reducing the likelihood of inflammatory-induced damage.

Hydration and barrier function

The skin's barrier function is essential for maintaining hydration and protecting against environmental aggressors. TFA-T2 enhances the skin barrier by promoting the synthesis of barrier lipids and proteins such as filaggrin, which are crucial for barrier integrity and function. Improved barrier function leads to better moisture retention, reducing transepidermal water loss (TEWL) and keeping the skin hydrated. This enhanced hydration helps in maintaining skin softness and suppleness, preventing dryness and the associated rough texture. Additionally, a strong barrier function provides a protective shield against external pollutants and pathogens, further supporting skin health.

Antioxidant activity

Oxidative stress, primarily caused by reactive oxygen species (ROS), is a significant factor in skin aging. TFA-T2 exhibits potent antioxidant properties, which help neutralize ROS and protect skin cells from oxidative damage. It enhances the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase. Furthermore, TFA-T2 activates the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a master regulator of the antioxidant response. Activation of this pathway leads to the upregulation of various antioxidant proteins, providing a comprehensive defense against oxidative stress. This antioxidant protection is crucial for preventing the damage caused by environmental factors such as UV radiation and pollution, which can lead to premature aging.

Proteomic and genomic effects

Advanced proteomic and genomic studies have provided insights into the molecular effects of TFA-T2 on the skin. Transcriptomic analyses reveal that TFA-T2 influences the expression of a wide array of genes involved in ECM organization, cell proliferation, and stress response. Proteomic studies complement these findings by showing alterations in the abundance of proteins related to these pathways. For instance, TFA-T2 upregulates key ECM proteins such as fibronectin and laminin, which are crucial for maintaining the structural and functional integrity of the dermal matrix. Proteomic data also indicate increased levels of growth factors and cytokines that support tissue repair and regeneration, highlighting the multifaceted role of TFA-T2 in skin health.


  1. LOING, E.; et al. Trifluoroacetyl-tripeptide-2 to target senescence for anti-aging benefits. Cosmetics and Toiletries. 2012, 127 (4).
  2. Das, M.; et al. Rejuvenation of metabolic cascades for controlling aging through bioactive compounds: a review. J Nutri Food Sci Forecast. 2018, 1 (1): 1003.
  3. Bezivin, C. U.S. Patent Application No. 15/124,717. 2017.
  4. Anton, J. M. G.; et al. U.S. Patent No. 9,725,483. Washington, DC: U.S. Patent and Trademark Office. 2017.

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