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SCIENTIFIC CONCEPT
Resveratrol-Lift cosmetic line is intended for women wanting to fight against the major signs of aging: lack of firmness, skin sagging and wrinkles.
Aging causes various changes in the organization of the extracellular matrix. Its components, and particularly the different collagens and hyaluronic acid, decrease drastically. Indeed, as cells age, they are less efficient at synthesizing these proteins. Furthermore, chronological aging and extrinsic aging impact several metabolic pathways, leading to an increase of extracellular matrix proteins degradation.
Consequently, at 40 years old, the skin has lost on average 40% of its firmness [1].
Caudalie has associated Vine Resveratrol with micro Hyaluronic Acids (Caudalie x Harvard University – Co-filed Patent No. 1555116 ) in order to boost: the synthesis of hyaluronic acid.
In addition to these two ingredients, a complex of Pro-Collagen Grape Peptides have been incorporated into the new Resveratrol-Lift collection. Clinical evaluations have demonstrated the strong efficacy of this range in enhancing dermal density, improving skin firmness, and reducing wrinkle appearance.
After applying the product for 56 days on non-sensitive skin (61%) and sensitive skin (39%), no increase in the number of comedones was observed. The product can be labeled as non-comedogenic. The dermatologist concluded the product demonstrated very good skin tolerance.
Table of content
PROBLEM
Why does skin lose firmness, density and smoothness with age?
Thanks to its unique organization, the skin is naturally firm and tight. However, the skin structure is affected by both chronological aging and external aggressions, leading to sagging and wrinkling. Indeed, at 40 years old, the skin has lost on average 40% of its firmness [1].
These changes are mainly caused by changes at the dermis level. The degradation of the extracellular matrix is increased while the aged fibroblasts are less efficient at synthesizing its components such as collagen and hyaluronic acid, causing a decrease of dermis density.
Collagen — the structural backbone of the dermis
Collagens are a major component of the extracellular matrix. Indeed, they represent 75% of the dry weight of the skin [2]. They play a crucial role in the composition and organization of the extracellular matrix, therefore in the skin's mechanical properties.
The different types of collagens
20 different collagens are expressed in the skin. Among them, the most abundant are: collagen I (80 to 90% of total collagen), collagen III (8 to 12%) and collagen V (less than 5%) [2].
Collagens are distributed throughout the skin: in the epidermis, the dermo-epidermal junction, the dermis and even the hypodermis (Table 1 and Figure 1). They are mainly synthesized by fibroblasts but some, like collagen IV or VII, are synthesized by keratinocytes.
Collagen Type | Localization |
|---|---|
I | Dermis |
III | Dermis |
IV | Basement membrane |
V | Papillary dermis, hair follicles, eccrine glands |
VI | Dermis, vasculature, hair follicles, nerves |
VII | Basement membrane to dermis |
VIII | Basement membrane zone of vascular endothelium |
XI | Dermis |
XII | Papillary dermis, hair follicles |
XIII | Dermal–epidermal junction, vasculature, nerves and hair follicles |
XIV | Reticular dermis |
XV | Dermal–epidermal junction |
XVI | Papillary dermis |
XVII | Basal keratinocytes |
XVIII | Basement membrane, vasculature, sebaceous gland, hair follicle cells, hypodermis |
Table 1: Different collagens found in the skin and their distribution [3].
At the dermo‑epidermal junction, type IV collagen forms a two‑dimensional network that constitutes the basement membrane, providing structural support to the epidermis [4]. Type VII collagen assembles into anchoring fibrils that connect the basement membrane to the underlying dermis [5]. Transmembrane collagens (types XIII and XVII) and multiplexins (types XV and XVIII) contribute to cell–matrix adhesion and to the mechanical stability of this interface.
Within the dermis, fibrillar collagens predominate [6]. Type I and III collagens make up the bulk of the extracellular matrix, imparting mechanical strength and elasticity to the skin. Type V collagen regulates fibril diameter, while type XI participates in fibril organization [7,8]. Fibril‑associated collagens (FACITs), particularly types XII, XIV, and XVI, ensure cohesion and interconnection between collagen fibrils and other matrix components [9]. Type VI collagen, characterized by its beaded filament structure, forms a supportive microfibrillar network linking fibrils to one another and to dermal cells [10].
Together, these collagen types maintain the structure, resilience, and functional integrity of the skin by ensuring mechanical and biological continuity across its different layers (Figure 1).
In addition to the various collagen types, each molecule is composed of three α‑polypeptide chains that assemble into a characteristic triple helix. Each collagen type is defined by the specific nature and combination of these α‑chains. For example, type I collagen is composed of two α1(I) chains and one α2(I) chain, forming a heterotrimeric structure that provides high mechanical strength. In contrast, type III collagen is a homotrimer consisting of three identical α1(III) chains, resulting in a more compliant organization essential for tissue flexibility and repair processes. This diversity in α‑chain composition underlies the distinct biophysical properties and biological functions characteristic of each collagen type [11].
Figure 1: Diversity of human skin collagen types classified by structural families and localization (adapted from [11]).
Collagen and aging
Aging causes major degradation and disorganization of collagen. Indeed, it has been estimated that collagen content decreases of 1% each year from 20 years old [12].
Increased degradation of collagen is the first reason of this diminished content. Matrix metalloproteinases (MMP) are enzymes involved in the degradation of collagen and other dermal extracellular matrix proteins. They are stimulated by chronological aging [13] and extrinsic factors [14,15] and lead to collagen fragmentation.
Simultaneously, collagen synthesis is significantly reduced in aged skin. For example it has been shown that synthesis of collagen type I and III decreases upon skin aging [16,17]. Also, a loss of collagen IV has also been observed in aged skin, leading to the flattening of the dermo-epidermal junction [18].
Hyaluronic acid
Generalities
Hyaluronic acid is a glycosaminoglycan, which represents nearly 0.05% of the skin dry weight [19,20]. It is mainly produced by fibroblasts, but also by keratinocytes, by enzymes called hyaluronan synthases. But hyaluronic acid's half-life is very short in the skin: it is degraded after one day [21].
It is a key molecule for skin moisture since it can bind 1000 times its weight in water. Also, as it is most abundant in the dermis, it plays a major role in the viscoelastic properties of skin [22].
Hyaluronic acid and aging
The amount of hyaluronic acid, as well as its quality, decreases upon aging. According to a study, it drops by 50% between 19 and 60 years old [23]. This decrease is particularly important in the epidermis [24]. This reduction results in loss of skin moisture and elasticity. The skin is less plumped.
ACTIVE
Vine Resveratrol + Micro Hyaluronic Acids + Pro-Collagen Grape Peptides
Caudalie has associated Vine Resveratrol, micro Hyaluronic Acids and Pro-Collagen Grape Peptides to fight against the major biological causes leading to loss of skin firmness. Caudalie has demonstrated that associating Vine Resveratrol and micro Hyaluronic Acids provides greater anti-aging benefits (Caudalie x Harvard University – Co-filed Patent No. 1555116).
Patented Association — Resveratrol + Micro Hyaluronic Acids (Caudalie x Harvard University – Co-filed Patent No. 1555116)
Vine Resveratrol and micro Hyaluronic Acids possess many anti-aging benefits for the skin. Based on these results, Caudalie decided to associate the two active ingredients and proved that their association showed even greater benefits.
Vine Resveratrol
Resveratrol is a natural polyphenolic antioxidant produced by plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. One of the most common botanical sources is vine; more specifically, vine shoot is particularly rich in resveratrol. Caudalie's stabilized Vine Resveratrol was added to the whole Resveratrol Lift collection.
Micro Hyaluronic Acids
The Resveratrol Lift collection features Hyaluronic Acids of low molecular weight (50 kDa) able to go deep into the skin. They possess both anti-aging and moisturizing benefits. Once in the dermis, micro Hyaluronic Acids stimulate proliferation of fibroblasts, responsible for the synthesis of extracellular matrix. Consequently, the production of collagen, elastin and hyaluronic acid is increased in the dermis. Micro Hyaluronic Acids also have a moisturizing effect, due to their great water-holding capacity.
Pro-Collagen Grape Peptides
Pro-Collagen Grape Peptides is a proprietary active ingredient obtained through bio-enzymatic hydrolysis of grape seed cake, a raw material naturally rich in plant proteins. Derived entirely from vine by-products and of 100% natural origin, it is manufactured in France using grape seeds sourced from Portugal. This process yields a concentrated active fraction rich in grape-derived peptides with a molecular weight below 3,500 Da, comprising up to 500 distinct peptide sequences, predominantly made up of 2 to 6 amino acids. To further enhance its anti-ageing efficacy, this complex is combined with two biomimetic peptides: Tripeptide-1 (GHK), a collagen type I biomimetic matrikine, and Hexapeptide-9 (GPQGPQ), a biomimetic sequence derived from collagen types IV and XVII. The synergy between these peptides enhances the anti-ageing and hydrating properties of the formulation, notably through the stimulation and support of 20 skin collagen chains. Clinical evaluations have demonstrated the efficacy of this peptide combination in improving dermal density, increasing skin firmness, and visibly reducing the appearance of wrinkles.
MECHANISM
How do the Resveratrol Lift actives restore firmness?
The Resveratrol Lift complex acts through multiple complementary biological pathways: activation of longevity proteins (SIRT1), neutralization of reactive oxygen species, protection of the extracellular matrix from enzymatic degradation (MMP-1), stimulation of de-novo collagen and elastin synthesis, boosting of hyaluronic acid production (HAS2), and retinol-like pathway activation without inflammatory response.
1. Activation of Sirtuin longevity proteins
Resveratrol is an efficient anti-aging natural compound. It is partly due to its ability to activate Sirtuin1 (SIRT1) [25–27]. This protein is known for its ability to regulate longevity and delay aging [28–30].
2. Antioxidant activity
Reactive oxygen species (ROS) are increased in aged skin cells and have a major impact on skin aging [31]. ROS are naturally present in the cell at a regulated level. However, exposure to some prooxidant environmental factors (UV, pollutants, cigarette smoke…) induces an overproduction of ROS. Furthermore, the internal antioxidant system is less efficient in aged cells [32]. When ROS are in excess inside the cell, oxidative stress occurs. ROS react with several cellular components (DNA, proteins, lipids), leading to cellular damage, disturbance of several biological pathways and consequently, skin premature aging [33].
Resveratrol's antioxidant activity has been largely demonstrated. Within the skin, Resveratrol has been shown to protect skin cells against ROS production induced by environmental factors such as UV and cigarette smoke [34–36].
3. Protection of extracellular matrix proteins from degradation
Matrix metalloproteinases (MMP) are enzymes involved in the degradation of the dermal extracellular matrix. It has been shown that ROS are responsible for the increase of MMPs expression [14]. Elevated MMP level is one of the main contributors of skin wrinkling and loss of firmness. Particularly, MMP-1 plays a critical role in collagen I degradation. Resveratrol has already been shown to reduce the expression of MMP-1 in fibroblasts [37].
4. Stimulation of de-novo extracellular matrix protein synthesis
In addition to its ability to protect skin extracellular matrix from degradation, Vine Resveratrol can promote synthesis of extracellular matrix components, including elastin.
5. Stimulation of hyaluronic acid production
Hyaluronic acid is crucial to a youthful skin appearance, particularly for a firm and wrinkle-free skin. However, the amount of hyaluronic acid drastically decreases with aging. The effect of Vine Resveratrol and micro–Hyaluronic Acid on hyaluronic acid production has been evaluated by David Sinclair's laboratory at Harvard. The expression of hyaluronan synthase 2 (HAS2), the major enzyme synthesizing hyaluronic acid, has been assessed. When tested individually, only micro–Hyaluronic Acid stimulates HAS2 expression. The combination of Vine Resveratrol and micro–Hyaluronic Acid further enhances HAS2 expression.
6. Collagen chain stimulation via peptide synergy
Pro-Collagen Grape Peptides has demonstrated the ability to stimulate 20 skin collagen chains through the synergistic action of grape-derived peptides and the biomimetic peptides GHK (Tripeptide-1) and GPQGPQ (Hexapeptide-9).
7. Retinol-like pathway activation without inflammation
The Resveratrol Lift Instant Firming Serum activates the biological marker CRABP‑II, a pathway also triggered by retinol, indicating a retinol-like mode of action. Critically, unlike retinol, the serum did not increase the expression of the inflammatory receptor IL‑1R1, suggesting an effective yet non‑irritating mode of action.
PROOF
In vitro, in tubo & ex vivo scientific evidence
Sirtuin1 activation
Caudalie Vine Resveratrol multiplies Sirtuin1 activity by 128. Sirtuin1 enzyme was incubated with its substrate and Vine Resveratrol at 500 ppm for 1 hour. The reaction generates a fluorophore. The fluorescent signal is recorded and proportional to SIRT1 activity. Data are the result of a pool of 2 experiments performed in triplicate. Statistical Mann-Whitney test: *** = p < 0.001.
Figure 2: Effect of Caudalie Vine Resveratrol on Sirtuin1 activity.
Antioxidant defense
Caudalie Vine Resveratrol's antioxidant activity has been proven in skin fibroblasts subjected to oxidative stress. Caudalie Vine Resveratrol is able to stimulate the cell's antioxidant defense through the stimulation of the antioxidant molecule glutathione (GSH) and the antioxidant enzyme heme-oxygenase 1 (HO-1).
MMP-1 reduction
Caudalie Vine Resveratrol significantly reduces MMP-1 synthesis by dermal fibroblasts in inflammatory conditions (−70%).
Elastin synthesis
Caudalie Vine Resveratrol increases elastin synthesis by up to 80% in human dermal fibroblasts.
Hyaluronic acid production — Patented association (Harvard Medical School)
The combination of Vine Resveratrol and micro–Hyaluronic Acid enhances HAS2 expression (+226%). Skin fibroblasts were treated for 24 hours with the different compounds. After RNA extraction, HAS2 expression was evaluated by RT-qPCR. Statistical t-test: = p < 0.05, ** = p < 0.001. This association of ingredients stimulates hyaluronic acid production by 3×.
Figure 3: Expression of HAS2 in skin fibroblasts after treatment with Vine Resveratrol and micro Hyaluronic Acids.
Pro-Collagen Peptides — collagen chain stimulation
Tested in vitro, Pro-Collagen Peptides stimulates 11 collagen chains:
Collagen chain | Stimulation |
|---|---|
COL1A1 | +59% |
COL4A5 | +1030% |
COL5A2 | +120% |
COL6A2 | +21% |
COL6A3 | +163% |
COL8A2 | +99% |
COL11A1 | +208% |
COL12A1 | +20% |
COL14A1 | +110% |
COL15A1 | +188% |
COL16A1 | +73% |
COL18A1 | +32% |
Table 2: Pro-Collagen Peptides in vitro collagen chain stimulation
Tested ex vivo, Pro-Collagen Peptides stimulates 9 collagen chains:
Collagen chain | Stimulation |
|---|---|
COL1A2 | +44% |
COL3A1 | +72% |
COL4A2 | +41% |
COL5A1 | +52% |
COL5A3 | +40% |
COL6A1 | +42% |
COL7A1 | +56% |
COL8A1 | +31% |
COL17A1 | +145% |
Table 3: Pro-Collagen Peptides ex vivo collagen chain stimulation
Full active combination — collagen IV & VII gene expression
The evaluation of the Resveratrol‑Lift active combination on fibroblasts in vitro showed an upregulation of gene expression, with a 3.95‑fold increase in collagen type IV and a 1.98‑fold increase in collagen type VII.
Figure 4: Collagen IV and collagen VII gene expression in fibroblasts in vitro.
Serum vs Retinol — ex vivo comparison
Human skin explants were treated for 48 hours with either the Resveratrol Lift serum or a formulation containing 0.3% retinol. The RVL serum significantly stimulates type I collagen synthesis, with a +36% increase (p<0.001) compared with +12% (p<0.001) for the retinol formulation, representing a three‑fold higher efficacy. The marker CRABP‑II was also induced under both conditions, with +96% (p<0.001) for retinol and +16% (p<0.001) for the RVL serum, indicating that the formula activates biological pathways like those triggered by retinol and can therefore be described as "“retinol‑like.” Unlike retinol, the RVL serum did not increase the expression of the inflammatory receptor IL‑1R1, suggesting an effective yet non‑irritating mode of action.
Figure 5: In situ visualization of several markers levels by epifluorescence microscopy.
RESULT
Clinical test results — Resveratrol Lift collection
Clinical evaluations have demonstrated the strong efficacy of the Resveratrol-Lift range in enhancing dermal density, improving skin firmness, and reducing wrinkle appearance. Results are presented per product.
Tolerance
After applying the product for 56 days on non-sensitive skin (61%) and sensitive skin (39%), no increase in the number of comedones was observed. The product can be labeled as non-comedogenic. The dermatologist concluded the product demonstrated very good skin tolerance.
22 volunteers; 28 days.
Consumer satisfaction
After 56 days of use: 100% felt skin nourished and moisturized, 97% found skin soft and comfortable, 91% stated skin texture refined and product did not leave a greasy film. Volunteers found skin elasticity was restored after 28 days of application.
32 volunteers, 56 days.
Clinical — Nourishing / Moisturizing Effect
After 1 hour: Tewameter® → 11% decrease in transepidermal water loss (11 volunteers). Corneometer® → 66% increase in skin hydration (10 volunteers).
Clinical — Anti-wrinkle & Smoothing
Short-term (1–4 h): anti-wrinkle −9% at 1 h, −8% at 4 h (77% vol.). Smoothing: roughness −9% at 1 h, −7% at 4 h (81%/71%).
Mid-term (28 d): wrinkle depth −7% (73% vol.). Roughness −6% (63%).
Long-term (56 d): crow's feet −14% (84% vol.). Smoothness +20% whole face (97%).
31–32 volunteers, 56 days.
Clinical — Firming
D28: +16% firmness (97%). D56: +33% firmness (100%).
31–32 volunteers, 56 days.
Clinical — Redensifying
D28: DUB® SkinScanner → dermis density +30% (97%).
29 volunteers, 28 days..
Tolerance
56 days on normal (9%) and dry skin (91%). Very good skin tolerance.
34 volunteers; 56 days.
Consumer satisfaction
100% felt skin firmer on arms and thighs at D28. At D56: 100% firmer across arms, thighs, chest, stomach, buttocks.
33–34 volunteers; 56 days.
Clinical — Firming
Thighs: +3.8% D28, +5.2% D56. Triceps: +8.6% D28, +10.3% D56.
34 volunteers; 56 days.
Tolerance
Non-comedogenic. Very good skin tolerance after 56 days.
23 volunteers, 28 days / 34 volunteers, 56 days.
Consumer satisfaction
Awakening: 97% comfortable, 94% moisturized. D28: 97% refined, nourished, supple, fresher. D56: 94% nourished, smoother, younger-looking; 91% firmer, plumped, revitalized.
34 volunteers; 56 days.
Clinical — Moisturizing
Hydration +87% at 4 h, +79% at 8 h.
34 volunteers; 56 days.
Clinical — Anti-wrinkle
Crow's feet −8% D28, −12% D56. Under-eye −3% D28, −10% D56. Nasolabial fold −10% D28, −21% D56. Upper lip −10% D28, −25% D56. Lower face ptosis −14% D28, −22% D56.
34 volunteers; 56 days.
Clinical — Lifting & Firming
Lifted +17% D28, +34% D56. Plumped +21% D28, +38% D56.
34 volunteers; 56 days.
Tolerance
Non-comedogenic. Very good skin tolerance at D28 and D56.
23 volunteers, 28 days / 32 volunteers, 56 days.
Consumer satisfaction
D28: 97% moisturized, healthy glow; 84% plumped. D56: 94% plumped, nourished, mattified; 91% lifted, moisturized; 90% firmer.
32 volunteers; 56 days.
Clinical — Nourishing / Moisturizing
1 h: TEWL −12% (11 volunteers). Hydration +56% (10 volunteers).
Clinical — Anti-wrinkle & Smoothing
D28: smoothness +19% (84%). D56: wrinkle −12% (84%), crow's feet −8%, smoothness +32% (100%).
32 volunteers; 56 days.
Clinical — Firming
D28: +12%. D56: +23%.
32 volunteers; 56 days.
Clinical — Redensifying
D28: dermis density +55% (100%). D56: +65% (100%).
32 volunteers; 56 days.
Tolerance
Non-comedogenic. Very good skin tolerance after 56 days.
23 volunteers, 28 days / 34 volunteers, 56 days.
Consumer satisfaction
D28: 100% instantly firmer, fine lines smoothed. D56: 100% firmer, younger, more bouncy.
30 volunteers; 56 days.
Clinical — Nourishing / Moisturizing
D1: TEWL −8%. Hydration +24%.
34 volunteers, 1 day.
Clinical — Anti-wrinkle & Firming
D56: firmness restored equivalent of 10 years (up to +45%). Wrinkles and expression lines −8%.
34 volunteers, 56 days / 30 volunteers, 56 days.
Tolerance
Very good skin and ocular tolerance after 56 days.
30 volunteers; 56 days.
Consumer satisfaction
D28: 100% hydration improved; 94% depuffing. D56: 90% eye bags reduced (fresh applicator); 90% eyelids firmer, fine lines smoothed.
30–31 volunteers; 56 days.
Clinical — Anti-wrinkle & Lifting
D56: crow's feet −12%. Under-eye −11%. Upper-lip −7.5%. Upper eyelid lifting +31%.
30 volunteers; 56 days.
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