Lancôme's Latest Research in 2025: Rose PDRN, a Novel Sustainable Active Ingredient Targeting the Root Mechanisms of Skin Aging

Lancôme's Latest Research in 2025: Rose PDRN, a Novel Sustainable Active Ingredient Targeting the Root Mechanisms of Skin Aging

PDRN, a recent hot topic among active ingredients, has gradually expanded from salmon sources to various plant sources and biosynthetic formulations. The most famous example is Lancôme's use of rose PDRN. Similarly, Lancôme has conducted numerous in vitro efficacy and mechanism studies on this ingredient, gradually discovering new directions for PDRN's action. The data and model studies in this article are based on literature published by Lancôme in November 2025, revealing the diversity of PDRN's mechanisms of action, which is worthy of our study.

Environmental stressors such as pollution and ultraviolet radiation, as well as intrinsic temporal factors, have a significant impact on skin aging and photoaging. Recent insights in longevity science emphasize that mitochondrial health, protein homeostasis, and autophagy balance are key processes for maintaining skin integrity. This study investigates the protective potential of a natural product—rose-derived polydeoxyribonucleotides—against mitochondrial dysfunction and autophagy dysregulation in primary human keratinocytes subjected to environmental stress (benzo[a]pyrene and UVA). PDRN was evaluated at concentrations of 0.1%, 0.05%, and 0.01%. Mitochondrial function was assessed by membrane polarization, ATP/ADP ratio, complex V levels, and citrate synthase levels. LAMP2A levels were quantified to assess the autophagy pathway. Supplementary analyses were performed on ex vivo human skin explants to assess oxidative protein damage (carbonylation), collagen I/III integrity, MMP1 and IL1a levels, and mitophagy markers (PINK1, PARK2). Results confirmed that PDRN significantly protected mitochondrial function, mitigated oxidative stress, and modulated autophagy-related pathways in all tested models. These findings highlight the ability of this novel natural product, a plant-derived PDRN, to mitigate environmental skin aging (and photoaging) by maintaining mitochondrial balance and regulating protein homeostasis, positioning rose-PDRN as a key active ingredient in skin cosmetic formulations targeting biomarkers for skin longevity.

Polydeoxyribonucleotides (PDRNs) are a mixture of deoxyribonucleotide polymers, generally known for their regenerative and anti-inflammatory properties. In recent years, they have received increasing attention due to their therapeutic potential in tissue repair and dermatology. With their potent wound-healing activity, PDRNs have been widely used in skin regeneration, both as cosmeceuticals and in medical aesthetic applications. Since skin aging and wound repair share common biological pathways, the mechanisms by which PDRNs are activated in tissue healing are also associated with combating skin aging. Furthermore, PDRNs' ability to modulate inflammatory responses and support DNA repair suggests they can effectively mitigate environmental damage caused by two major external aging factors: pollutants and ultraviolet radiation. Through these processes, PDRNs not only promote the regeneration of damaged skin tissue but also help protect skin integrity from external stressors. PDRNs are typically obtained from salmon sperm, primarily rainbow trout and red trout. However, this source is limited by seasonal availability, high cost, and ethical concerns. These limitations underscore the need for effective, sustainable, and ethically acceptable non-animal alternatives to traditional salmon-derived PDRNs. Other sources have been explored, including marine organisms such as starfish and sea cucumbers, and plant sources such as red algae and ginseng. These non-salmon-derived PDRNs have shown antioxidant, anti-inflammatory, and regenerative effects comparable to fish-derived PDRNs in skin models. Therefore, rose-derived PDRN represents a novel, sustainable, plant-based alternative with broad potential in skin cosmetics.

This study investigated the protective effects of rose-derived PDRN on mitochondrial function, autophagy, and oxidative homeostasis in keratinocytes and human skin explants exposed to BaP/PM10 and UVA. By targeting aging markers, rose-derived PDRN appears to be a promising strategy for protecting skin longevity.

Mitochondrial function is crucial for skin health, supporting regeneration, differentiation, and extracellular matrix maintenance. Key indicators such as mitochondrial membrane potential, ATP/ADP ratio, complex V activity, and citrate synthase reflect cellular bioenergetics. Their decline is associated with accelerated aging, impaired renewal, and reduced barrier function. Therefore, maintaining mitochondrial integrity is a key strategy for maintaining skin longevity.

Meanwhile, autophagy, particularly mitophagy, ensures skin homeostasis by clearing damaged organelles and proteins. Molecular chaperone-mediated autophagy, regulated by LAMP2A, protects cells from protein toxicity stress and contributes to mitochondrial quality control. However, environmental stress and aging impair CMA, leading to protein aggregation, mitochondrial dysfunction, and reduced resilience.

Mitochondrial quality control also relies on PINK1/Parkin-mediated mitophagy and PGC-1α-driven mitochondrial biosynthesis. While these systems are generally adaptable to stress, prolonged exposure to UVA or pollutants inhibits them, impairing cellular defenses and promoting premature aging. PINK1/Parkin coordinates ubiquitin-dependent mitophagy, targeting damaged mitochondria for macroautophagic clearance, while the CMA's lysosomal receptor LAMP2A mediates the selective degradation of soluble cytoplasmic proteins with KFERQ-like motifs. These pathways represent different branches of the autophagy network.

Environmental stressors such as UVA, PM10, and PAHs accelerate oxidative damage, upregulate MMP1, and trigger pro-inflammatory cytokines like IL-1α. These processes fragment collagen fibers, weaken dermal structure, and amplify age-related secretory phenotypes, key drivers of skin aging.

Another hallmark is the loss of protein homeostasis, typically measured by protein carbonylation (an irreversible oxidative modification). The accumulation of carbonylated proteins reflects a decline in detoxification and scavenging mechanisms, linking oxidative stress to matrix degradation, inflammatory aging, and senescence.

This study demonstrates that plant-based PDRN extracted from hybrid rose provides robust mitochondrial protection, supports autophagy homeostasis, and mitigates environmental stressor-induced oxidative damage. By targeting the root molecular causes of skin aging, rather than its surface manifestations, these findings propose an effective strategy for promoting long-term skin resilience and longevity. Therefore, rose-derived PDRN represents a new generation of longevity-inspired ingredients designed to mitigate environmentally accelerated skin aging while cultivating regenerative capacity, delaying cellular senescence, and supporting long-term skin health and longevity.

In Vitro Assessment (Human Keratinocytes)

1. Mitochondrial Membrane Polarization
Primary human keratinocytes were exposed to environmental stressors (BaP + UVA) and/or treated in vitro with three different concentrations of rose PDRN. Primary human keratinocytes were exposed to BaP + UVA with or without rose PDRN pretreatment. Mitochondrial function, reflecting membrane polarization, was assessed using Mitotracker® fluorescence.

Rose PDRN pretreatment preserved mitochondrial integrity and mitigated the negative effects of stress, demonstrating benefits for mitochondrial integrity and function under stress: 94% efficacy (0.1%), 100% (0.05%), and 88% (0.01%).

2. Autophagy and Mitophagy
LAMP2A levels were monitored to assess autophagy, visualized and quantified using in situ immunofluorescence (on cells). BaP + UVA exposure significantly increased LAMP2A levels, consistent with the activation of autophagy mechanisms in response to cellular stress. Rose PDRN pretreatment prevented this increase, maintaining LAMP2A levels close to control (89% at 0.1%, 100% at 0.05%, and 86% at 0.01%), thus supporting autophagy homeostasis and mitochondrial integrity.

3. Mitochondrial Function and Content
To further validate the beneficial effects of rose PDRN on mitochondrial preservation, additional analyses were performed using 0.05% and 0.01% concentrations. Mitochondrial function was assessed by measuring CV-ATP5A, ATP/ADP ratio, and citrate synthase. Rose PDRN (0.05%, 0.01%) enhanced these parameters under basal conditions, increasing CV-ATP5A (induced +41%, +22%), ATP/ADP ratio (+36%, +60%), and CS (+30%, +11%).

BaP + UVA stress reduced all three markers, while rose PDRN pretreatment significantly preserved them: CV-ATP5A (42%, 33% protective efficacy), ATP/ADP ratio (completely restored to control levels), and CS (64%, 45% efficacy). These results reinforce the ability of rose PDRN to maintain mitochondrial bioenergetics and structural integrity under oxidative stress.

Ex vivo (skin explant) assessment

1. Mitochondrial function
The efficacy of rose PDRN under PM10 + UVA stress was confirmed using an ex vivo 3D human skin model. Citrate synthase levels, as measured by immunofluorescence, were significantly reduced by stress but were preserved by rose PDRN pretreatment (25% efficacy at 0.1%, 53% at 0.05%), consistent with the protective effect observed in keratinocytes.

Citrate synthase is visualized in magenta. LAMP2A is visualized in green. Immunofluorescence images show skin explants after stress exposure. Nuclear detection (DAPI, cyan) is overlaid. Epidermis and dermis are separated by white dashed lines.

2. Autophagy and Mitochondrial Homeostasis

In skin explants, stress (PM10 + UVA) exposure significantly increased LAMP2A levels (top panel). Rose PDRN pretreatment prevented this increase, preserving LAMP2A at 86% of the control level (both 0.1% and 0.05%), indicating a reduced need for compensatory autophagy and preservation of skin and protein homeostasis.

PINK1, PARK2, and PGC1α on skin sections were subsequently assessed by immunofluorescence analysis (bottom panel) to further investigate the effects of stressors and rose PDRN on other key markers of mitochondrial homeostasis. Stress (PM10 + UVA) reduced PINK1 and PARK2 levels, while rose PDRN partially preserved them (PINK1: 9% efficacy at 0.1%, 5% at 0.05%; PARK2: 54% and +45%, respectively).

Mitochondrial quality control also depends on PINK1/PARK2-mediated mitophagy, which coordinates ubiquitin-dependent clearance of damaged mitochondria via macroautophagy. Their significant reduction under stress indicates impaired mitophagic capacity, while their partial preservation by rose PDRN suggests improved mitochondrial surveillance and more efficient clearance of dysfunctional mitochondria. This is consistent with the preservation of mitochondrial function and reduction of stress-induced oxidative damage observed in PDRN-pretreated samples before stress exposure.

PGC1α levels were significantly increased by stress exposure, but this increase was mitigated by rose PDRN (16% at 0.1%), indicating reduced mitochondrial damage and a decreased need for compensatory biosynthesis.

3. Assessment of SASP Markers and Dermal Matrix Integrity

To investigate the effects of rose PDRN on SASP markers and dermal matrix integrity under environmental stress, the levels of IL-1α and MMP1, as well as the structural integrity of collagen I and III, were assessed using immunofluorescence analysis in an ex vivo skin model.

As expected, IL-1α and MMP1 significantly increased after stress exposure, while collagen I and III significantly decreased. Rose PDRN completely alleviated IL-1α induction (100% efficacy), significantly reduced MMP1 levels (81% at 0.1% and 58% at 0.05%), and preserved collagen integrity, maintaining collagen I (81% at 0.1% and 100% at 0.05%) and collagen III (100% at both concentrations). These findings highlight the ability of rose PDRN to counteract SASP activation and confirm its potential to protect and maintain dermal structure.

IL-1α signaling on skin explant sections is visualized in magenta (A), MMP1 signal in orange (B), collagen I in yellow (C), and collagen III in green (D). Nuclear detection (DAPI, cyan) is overlaid. The epidermis and dermis are separated by a white dashed line. The levels of each biomarker are shown as relative values ​​in a bar chart and are presented as mean ± SD for each experimental group.

4. Protein Homeostasis and Oxidative Stress

To further confirm the protective effect of rose PDRN on cellular and tissue homeostasis, in situ protein carbonylation levels in skin sections were assessed.

As expected, exposure to stress resulted in a significant increase in protein carbonylation levels in all skin compartments (stratum corneum, epidermis, and dermis), indicating that extensive oxidative damage extends to deeper layers of the skin. Rose PDRN pretreatment significantly reduced carbonylation in the stratum corneum (54%, 53% efficacy), epidermis (45%, 41%), and dermis (56%, 46%) at concentrations of 0.1% and 0.05%, resulting in overall protein homeostasis maintained at approximately 45–47%.

Carbonylation levels were visualized in situ by epifluorescence microscopy (red). Nuclear detection (DAPI, cyan) was overlaid. Epidermis and dermis were separated by white dashed lines. The carbonylation quantification levels for each experimental group are shown as relative values ​​(% vs. control) in a bar chart and are presented as mean ± SD. Exposure to stress (pollution; PM10 + UV-A) increased in situ carbonylation levels in the stratum corneum, epidermis, and dermis. Rose PDRN, at both tested concentrations, showed a significant beneficial effect, offsetting the effects of stress (*** p < 0.001).

These results demonstrate that rose-derived PDRN effectively counteracts environmental stress-induced damage to keratinocytes and human skin explants, highlighting the novelty of rose-derived PDRN and confirming its value as a plant-based alternative to traditional salmon-derived PDRN, thus providing sustainability and broad applicability for skin cosmetics.

This study provides insights into the cellular and molecular mechanisms by which a novel natural product—rose-derived polydeoxyribonucleotides—exerts beneficial effects and promotes skin longevity. Indeed, the results indicate that environmental stressors such as PM10, BaP, and UVA radiation impair mitochondrial function, autophagy homeostasis, and protein homeostasis by generating reactive oxygen species.