 Next‑generation photo‑protection, which I prefer to call “DNA-care”, begins where classic UV-filers stop: at the level of DNA repair, antioxidant defence, and selective interaction with the full light spectrum. Instead of simply blocking radiation, advanced strategies aim to pair DNA repair technologies with powerful antioxidants to neutralise reactive oxygen species from both UV and visible light, while still allowing beneficial wavelengths such as infrared and near‑infrared to support the skin’s intrinsic vitality. Within this context, the concept of the skin interactome offers a powerful framework, revealing how genome, microbiome, and exposome dynamically interact to shape not only current skin health, but also the trajectory of skin ageing over time. The skin interactome is an integrative framework that captures the complex and dynamic interactions between the genome, microbiome, and exposome to provide a comprehensive understanding of skin biology and health. Unlike traditional approaches focusing on single factors, the interactome highlights how genetic predispositions, resident microbial communities, and environmental and lifestyle exposures collectively influence skin function, health, and needs. This holistic concept provides an excellent framework for skin research as it guides the development of personalised, next-generation sunscreens (or DNA-care) and skincare products that do so much more for skin health than hydrate or block UV rays as they optimise the skin’s protective, reparative, and homeostatic functions.  GENOME, EPIGENOME, MICROBIOME, PROTEOME, INFLAMMASOME, AND EXPOSOME INTERPLAY The genome includes the individual's genetic makeup like skin type, skin tone and the regulatory pathways that dictate responses to UV radiation, DNA repair mechanisms, pigmentation synthesis, and inflammation. Gene activity is dynamically regulated by epigenetic mechanisms such as DNA methylation and histone modifications which are reversible and sensitive to environmental (exposome) and microbial (microbiome) stimuli. Epigenetic modifications mediate how external factors like UV exposure, pollution, and lifestyle and skincare routines influence gene expression without altering the DNA sequence itself. The skin microbiome is made up of many different bacteria, fungi, and viruses living on our skin. It plays an important role in regulating immune responses, protecting the skin barrier, and managing oxidative stress. The makeup of these microorganisms varies depending on skin type, like oily or dry skin, and this balance influences overall skin health. The microbiome interacts closely with the skin’s epigenetic system or epigenome. Microbes produce metabolites and signals that can change epigenetic markers; chemical tags on DNA or proteins that control how genes are switched on or off. At the same time, changes in the skin’s epigenetic landscape shape the environment where microbes live, affecting which microorganisms thrive. This two-way interaction is essential for maintaining healthy skin and affects the likelihood of developing skin diseases.  Inflammasomes are multi-protein immune complexes within keratinocytes and immune cells, act as sensors for endogenous and exogenous danger signals including microbial components and environmental insults such as UV-induced oxidative stress. Activation of inflammasomes like NLRP3 triggers the release of pro-inflammatory cytokines (e.g., IL-1β), orchestrating innate immune responses. Dysregulated inflammasome activity driven by microbial imbalance or exposomic factors can lead to chronic inflammatory skin conditions, accelerates photoaging and skin cancer development. The proteome is the full set of proteins expressed by the genome at a given time, executing critical skin functions, including barrier formation, antioxidative defense, DNA repair, and signaling. Proteome composition and activity are tightly controlled by epigenetic regulation and can be modulated by inflammasome-induced inflammatory pathways. Consequently, the exposome’s influence permeates through genome, epigenome, microbiome, inflammasome activation, and proteome dynamics to collectively shape skin phenotype and responses. SKIN INTERACTOME COMPONENTS AND INTERACTIONS Next-generation photo-protection should consider the broader impact of the skin interactome including genome, microbiome, inflammasome, proteome, and exposome factors. COLLAGEN EXAMPLE  KEY EXAMPLES ▌Visible light protection: Visible light (VL), particularly blue light, penetrates deeper into the skin and can induce pigmentation changes (especially in darker phototypes), oxidative stress, and inflammation. Standard sunscreens often lack effective VL protection. Innovations such as tinted sunscreens containing iron oxides and pigmentary titanium dioxide are being developed to protect the skin from visible light-induced damage and pigmentation. VL defense can be offered by a specific anti-oxidant (licorich root extra) which has proven to effectively reduce ROS from VL, thus reducing the damage. ▌Genetic and molecular photoprotection: Genetic variants, such as those affecting melanocortin 1 receptor (MC1R) signaling, which not only determine pigmentation but also regulate antioxidant defences and DNA repair in melanocytes, critical for photoprotection. Understanding these genomic determinants enables personalised formulation development to enhance antioxidant defences and DNA repair mechanisms crucial for healthy skin. ▌Microbiome-targeted sunscreens: The skin microbiome contributes to skin homeostasis and immune regulation, modulating inflammation and barrier function. Next-generation sunscreens or DNA-care should aim to protect or even positively modulate the microbiota, reducing microbial imbalance (dysbiosis) and associated inflammation. In oily skin, increased sebum production creates an environment favorable to Cutibacterium acnes strains that produce elevated levels of porphyrins, bacterial metabolites linked to skin inflammation. Specific acne-associated strains, such as IA-2, IB-1, and IC, enhance porphyrin production, which promotes inflammatory responses. UV-B radiation suppresses porphyrin synthesis, contributing to antibacterial effects, while violet-blue light excites porphyrins to generate reactive oxygen species, useful for photodynamic therapy but potentially causing skin damage and hyperpigmentation, especially in darker phototypes. This example illustrates how exposome factors (light exposure) interact with the microbiome and genome-driven sebum secretion to influence skin inflammation and photoprotection needs in oily skin. ▌Inflammasome modulation: Environmental triggers and microbial dysbiosis can activate inflammasomes, promoting chronic inflammation and accelerating photoaging and carcinogenesis. Photoprotection is evolving to include ingredients that reduce inflammasome activation, thus addressing immune-mediated skin damage. ▌The exposome induces activation of the proteome components matrix metalloproteinases (MMPs), including collagenase, hyaluronidase, and elastase, which collectively degrade key extracellular matrix (ECM) proteins such as collagen, elastin, and hyaluronic acid, leading to disruption of ECM integrity and impaired skin structural homeostasis and cause premature skin aging. ▌Lifestyle and environmental interventions: Factors like diet, sleep quality, and pollution exposure also influence skin inflammation, oxidative status and cause microbial shifts. Integrated skincare strategies supporting antioxidant capacity complement physical photoprotection. ▌In oily skin (genome), increased sebum production leads to elevated levels of lipids susceptible to oxidative damage. Exposure to UV and visible light (exposome) promotes reactive oxygen species (ROS) formation, which initiates lipid peroxidation predominantly targeting sebum components like squalene. This lipid peroxidation disrupts the integrity of skin cell membranes (proteome effect), increases inflammation, and contributes to accelerated skin aging. The resulting oxidative stress can overwhelm antioxidant defenses (epigenetics), creating a vicious cycle that further impairs skin health. These examples illustrate the complexity of the skin interactome and the necessity of multifunctional, personalized photoprotection products that go beyond UV blocking to comprehensively preserve and restore skin health. Next-generation sunscreens or DNA-care should offer a comprehensive and personalised approach that integrates the complexity of the skin interactome and real-world lifestyle factors:  15 PILLARS OF ADVANCED SUNSCREEN DNA-CARE TECHNOLOGY ▌Tailored formulations: Customize based on genome and phototype to optimize DNA repair, pigmentation, and barrier function, addressing genetic variations like MC1R and sebum levels linked to skin type. ▌Broad-spectrum environmental defense: Protect against damaging UV, visible light (notably blue light), and pollution using broad-spectrum filters combined with powerful antioxidants that neutralize reactive oxygen species generated by these exposomic factors. However, it should leverage the benefits sun has to offer like infrared and near infrared. ▌Microbiome support: Include prebiotics, postbiotics, and microbiome friendly formulations to maintain a balanced skin microbiota, reduce inflammation, and enhance skin barrier resilience. ▌Inflammasome modulation: Incorporate actives that prevent or reduce inflammasome activation to minimize chronic inflammation, photoaging, and skin carcinogenesis. ▌Proteome protection: Inhibit proteolytic enzymes such as matrix metalloproteinases (MMPs), collagenase, elastase, and hyaluronidase to preserve extracellular matrix proteins (collagen, elastin, hyaluronic acid), maintaining skin structure and preventing premature aging. ▌DNA repair enhancement: Support natural DNA repair pathways with enzymes or boosting actives to repair UV-induced genetic damage. ▌Oxidative stress reduction: Provide an antioxidant-rich composition that targets pollution-induced oxidative damage, supporting skin exposed to urban or high-pollution environments. ▌Nutrient delivery synergy: Combine topical antioxidants with ingredients that complement dietary antioxidants (vitamins C, E, polyphenols), enhancing systemic and topical skin repair. ▌Adaptive and lifestyle-responsive formulations: Formulate variations tailored to pollution levels, climate, user habits, and skin conditions (e.g., more hydration for dry or sleep-deprived skin, lighter textures for oily skin), enabling personalized skincare regimens. ▌Smart usage guidance: Deliver personalized advice on sunscreen reapplication and complementary lifestyle and skincare routines aligned with individual factors such as sleep quality, diet, UV exposure, and pollution levels. ▌Circadian rhythms alignment: Design formulations that respect skin’s biological clock, optimizing sleep, protection and repair cycles for maximal effectiveness. ▌Hydration and barrier strengthening: Incorporate moisturizing, barrier-repair agents customized to skin needs and environmental stressors to support epidermal health. ▌Epigenetic modulation through active ingredients that reactivate protective gene expression by reversing harmful DNA methylation and histone modifications, preventing epigenetic damage from UV and environmental stressors. ▌The product should seamlessly integrate as the final, complementary step in a personalized morning skincare routine tailored to individual skin type and concerns such as pigmentation, photoaging, and skin cancer prevention, offering a pleasant, invisible texture without any pilling. ▌The product should maintain and improve overal skin quality and health.  This holistic, personalized strategy ensures that sunscreens not only prevent sun damage but also actively enhance skin health and quality by addressing molecular, microbial, environmental, and lifestyle complexities. I am confident that as scientific insights and knowledge evolve, I will continue to refine and complement this holistic approach.
Take care. Anne-Marie ACKNOWLEDGEMENT ▌The key scientific reference and accompanying illustrations used here are adapted from: Khmaladze et al. The Skin Interactome: A Holistic "Genome-Microbiome-Exposome" Approach to Understand and Modulate Skin Health and Aging. Clin Cosmet Investig Dermatol. 2020.pmc.ncbi.nlm.nih ▌"Skin Quality – A Holistic 360° View: Consensus Results" Authors include Heather C. Woolery, Martina Kerscher, and others. Published in Clinical, Cosmetic and Investigational Dermatology, 2021. Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214518/
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