(1) Background: Environmental factors, such as airborne pollutants and solar UV, induce oxidative damage to proteins and lipids on hair fibers, leading to decreased hair strength and shine, increased fiber porosity, brittleness, dryness, and stiffness. Traditional methods used for hair damage/protection/reparation assessment show limitations in sensitivity or specificity for evidencing the benefits to be gained from the protection/reparation of hair fibers against environmental stressors. (2) Methods: Ex vivo experimental models of hair fibers exposed to urban pollutants and UV irradiation were developed. Targeted proteomics approaches for the quantification of oxidatively damaged (carbonylated) proteins on hair fibers were optimized. (3) Results: A significant dose-dependent increase in carbonylation both in the cuticle and cortex proteins was observed upon exposure of hair fibers to particulate matter and UV-A radiation, at daily stress equivalent doses. Increased protein carbonylation on keratins and keratin-associated proteins led to loss of hair fiber structural integrity. The oxidative modification of proteins induced by urban pollution exposure led to hair cuticle structural damage revealed by an increased permeability. However, protein carbonylation was prevented in the presence of antioxidant compounds. (4) Conclusions: Protein carbonylation is an early event in hair fiber damage which can be used as a reliable biomarker for the efficacy of hair care interventions against environmental stressors.

(1) Background: Skin undergoes constant changes, providing capabilities to repair and renovate its constituents once damaged and a fundamental shield to contrast environmental stress. Nevertheless, environmental stressors may overcome the skin’s protective potential inducing premature aging and accelerating the appearance of anaesthetic age-related skin aspects. Ultraviolet radiation (UVR) and pollutants (particulate matters, PAHs) contribute to skin aging and functional decline inducing harmful oxidative modifications of macromolecules and stress-related skin disorders. Innovative approaches to preserve skin are needed. (2) Methods: Skin keratinocytes were treated (or not) with a combination of ingredients (Lactobacillus plantarum extract, Withania somnifera root extract and Terminalia ferdinandiana fruit extract; “MIX”) in the presence or absence of stress (oxidative stress or pollution). The effects of the MIX adaptogen technology on (a) cellular resilience, (b) the regulation of cellular functions and (c) regeneration of skin were disclosed through expression proteomics and bioinformatics analyses first, and then through focused evaluations of protein carbonylation as a hallmark of oxidative stress’ deleterious impact and mitochondrial activity. (3) Results: The deleterious impact of stressors was evidenced, as well as the beneficial effects of the MIX through (a) mitochondrial activity preservation, (b) the “vigilance” of the NRF2 pathway activation, (c) NADPH production and protein homeostasis improvements, (d) preserving skin regeneration function and I the contrasting stress-induced oxidation (carbonylation) of mitochondrial and nuclear proteins. (4) Conclusions: The effects of the MIX on increasing cell adaptability and resilience under stress suggested a beneficial contribution in precision cosmetics and healthy human skin by acting as an adaptogen, an innovative approach that may be employed to improve resistance to harmful stress with a potential favourable impact on skin homeostasis.

Environmental stressors such as pollution and ultraviolet (UV) radiation contribute significantly to skin aging and skin photo-aging, alongside intrinsic chronological factors. Recent insights into longevity science have emphasized mitochondrial health, proteostasis, and autophagic balance as critical processes for maintaining skin integrity. This study investigates the protective potential of a natural product, Rose-derived PolyDeoxyRiboNucleotide (PDRN), against mitochondrial dysfunction and dysregulated autophagy in primary human keratinocytes subjected to environmental stress (benzo-a-pyrene and UV-A). PDRN was evaluated at 0.1%, 0.05%, and 0.01% concentrations. Mitochondrial function was assessed through membrane polarization, ATP/ADP ratio, Complex V (CV-ATP5A) levels, and citrate synthase levels. LAMP2A levels were quantified to evaluate the autophagic pathway. Complementary analyses were performed on ex vivo human skin explants, evaluating oxidative protein damage (carbonylation), Collagen I/III integrity, MMP1 and IL1a levels, and mitophagy markers (PINK1, PARK2). The results confirm significant protection of mitochondrial function, attenuation of oxidative stress, and modulation of autophagy-related pathways by PDRN across all models tested. These findings underscore the capacity of this novel natural product, a plant-derived PDRN, to mitigate environmental skin aging (and photo-aging) through mitochondrial maintenance and proteostasis regulation, positioning Rose-PDRN as a key active ingredient for dermocosmetic formulations targeting skin longevity biomarkers.

The skin is continuously exposed to environmental changes, rendering it vulnerable to damage from external stressors that contribute to premature skin aging. This study aims to explore skin longevity pathways stimulated by a rose extract (RE) derived from petals. Human keratinocytes treated with RE exhibited a significant increase in NRF2 (NF-E2-related factor 2; ≈2–4% of induction) and LAMP2A (Lysosome-Associated Membrane Protein 2A; ≈6–12% of induction) levels. The presence of RE significantly mitigated the increase in carbonylation levels (≈34–37% of protection) and the number of labeled P16^INK4A cells (≈60–72% of protection), associated with proliferation arrest, both induced by exposure to BAP (Benzo[a]pyrene) coupled with UV-A (Ultraviolet A) irradiation. The beneficial effects mediated by RE were inhibited by Compound C, a specific AMPK inhibitor (AMP-activated protein kinase). The involvement of the AMPK pathway in mediating the beneficial effects of RE has been confirmed by assessing its activation through the evaluation of its phosphorylation state which was significantly elevated in the presence of RE compared to the stress condition. In conclusion, the activation of the AMPK pathway enhances antioxidant defenses and promotes autophagy. This dual action, mediated by RE, helps protect skin cells from oxidative damage and senescence while maintaining proteostasis, skin integrity, and cellular proliferation under pollution-induced stress (BAP + UV-A). These findings highlight the potential in mitigating age-related skin changes through the modulation of longevity pathways.

Protein carbonylation (PC) is a marker of reactive oxygen species-mediated alterations induced by external stimuli such as UV and blue light irradiation. In this study, we investigated the protective effect of Vitachelox^®, a mixture of three standardized natural extracts rich in polyphenols, against PC induced by blue light irradiation in human keratinocytes. We tested eight experimental conditions, including Vitachelox^® 0.01% and 0.005% w/v, used for 6 or 24 h before irradiation, and a solution of N-acetylcysteine (NAC) as positive control of protection. PC was evaluated by fluorescence microscopy in situ and by absolute quantification (Carbonyl Score) upon protein extraction and separation. Both the in situ visualization study and the carbonyl score showed a considerable increase in protein oxidative damage upon blue light irradiation, and a decrease in PC in the presence of Vitachelox^®. In particular, Vitachelox^® 0.005% showed superior results compared to NAC in terms of carbonyl score and protein quality, and it was estimated to exert a protective action against blue-light irradiation ranging from 72% (24 h) to 82% (6 h). The protective antioxidant effect of Vitachelox^®, together with the anti-inflammatory and anti-microbial properties previously reported, make this natural active ingredient a valuable tool in the maintenance of healthy skin.

Maintaining a balanced skin microbiota is essential for preserving epidermal barrier integrity and overall skin health. Dysbiosis, particularly the opportunistic overgrowth of Staphylococcus aureus, is associated with barrier dysfunction and inflammatory dermatoses such as atopic dermatitis, psoriasis, and acne. In dysbiotic states, microbial regulatory mechanisms become disrupted, enabling pathogenic strains to proliferate and release proteases that degrade structural components of the skin barrier, increasing epidermal permeability in a manner analogous to ‘leaky gut’ physiopathology. Microbiota dysbiosis has further been proposed as an emerging hallmark of aging, contributing to chronic low-grade inflammation, impaired tissue repair, and progressive barrier decline. Current strategies predominantly target the microbiota itself, leaving the host tissue response to protease-mediated barrier disruption comparatively underaddressed. To fill this gap, an ex vivo human skin model was developed based on topical application of purified S. aureus serine protease SspA to skin explants, enabling controlled investigation of early host–microbiota interaction events. Barrier function, junctional integrity, inflammatory mediators, and proteostasis were assessed through a panel of complementary biomarkers—Lucifer Yellow permeability, claudin-1, desmoglein-1, filaggrin, IL-31, S100A8/A9, PGE2, and protein carbonylation. SspA induced measurable barrier disruption, junctional protein loss, inflammatory mediator upregulation, and proteostasis impairment without overt tissue damage. A biotic culture filtrate of Bifidobacterium adolescentis partially attenuated SspA-induced protein carbonylation. This model provides the scientific community with a controlled, biologically relevant platform for identifying biomarkers of early barrier impairment and evaluating host-targeted interventions aimed at preventing or counteracting protease-driven barrier damage in dysbiosis-associated skin conditions. A better understanding of the early molecular mechanisms through which microbial virulence factors drive barrier disruption and proteostasis decline may further contribute to broader strategies aimed at preserving skin integrity during aging.