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The reality is, we are all aging. But what is the exact biological impact of this process on the skin? Modern longevity science has moved beyond surface-level aesthetics, mapping out precisely what happens at a cellular level as humans age [1]. For brands, formulators, and professionals in the dermatology and cosmetics space, understanding these biological root causes is essential for developing the next generation of scientifically-backed products [2]. The Biological Criteria for Aging Before exploring specific mechanisms, it is important to understand how scientists classify these biological processes. To be officially recognised as a "hallmark" of aging, a physiological process must meet three strict criteria [3]: Age-associated manifestation: The biological issue must clearly appear and progressively worsen as organisms get older. Acceleration by experimental accentuation: If intentionally triggered or worsened in a laboratory setting, it must cause rapid, accelerated physical aging. Opportunity for intervention: If a therapeutic or cosmetic treatment targets this specific problem, it must result in a measurable slowing or reversal of aging markers. The 12 Hallmarks of Aging: An Overview In 2013, the foundational "Hallmarks of Aging" were defined by researchers. Over the past decade, extensive scientific validation expanded this list, bringing the total to twelve fundamental processes in 2023 [3]: Fig 1. The Hallmarks Of Aging Deep Dive: 5 Crucial Mechanisms Driving Skin Aging For personal care and cosmetics formulation, certain biological hallmarks have a substantial impact on the skin's visible aging timeline. Here is a closer look at the five mechanisms that represent the frontier of longevity skincare. 1. Chronic Inflammation ("Inflammaging") What it is: "Inflammaging" is the result of long-lasting, low-level inflammation throughout the body. Over time, this constant state of stress makes it much harder for the skin to heal and renew itself [3,4]. Why it matters for skin: This causes the skin to break down its collagen and elastin, weaken its protective barrier, and heal much slower, directly leading to wrinkles, sagging, dryness, and an uneven tone. Fig 2. Inflamm-aging in the Skin 2. Dysbiosis What it is: Dysbiosis is a structural imbalance within the skin’s microbiome. In a healthy state, diverse populations of beneficial microorganisms coexist to protect the skin [5]. Why it matters for skin: As we age, our skin's physical composition undergoes significant changes that alter the "microenvironment" where these microbes live. This factor causes: Decreased Lipid Production: A reduction in natural oils (sebum) removes a primary nutrient source for beneficial bacteria. Diminished Hydration: Lower moisture levels create a drier, more difficult environment for microbes to survive. Barrier Fragility: A weakened physical defense layer makes the skin more susceptible to external stressors (like UV damage) and instability [6]. (fig. 3) Fig 3. Impact of the Skin Microbiome on Wrinkle Formation and Potential Modulation During Aging 3. Altered Intercellular Communication What it is: To stay healthy, the body's cells constantly send messages to each other. As you age, this communication breaks down, weakening the immune system and making it harder for the body to heal and protect itself [3]. Why it matters for skin: Healthy skin relies on different layers of cells talking to each other to produce collagen and keep the skin strong. When this communication breaks down, the skin struggles to heal or protect itself from sun damage, which leads to a weaker barrier and easier bruising [7]. 4. Loss of Proteostasis What it is: Proteostasis is the cells' recycling center, responsible for building and breaking down proteins (collagen, elastin and keratin). When it stops working properly, damaged proteins pile up and create a mass amount of toxic cellular waste [3]. Why it matters for skin: The buildup of this cellular waste creates an unhealthy environment that weakens the cells. As a result, the skin loses its natural radiance and its ability to remain firm and elastic [8]. 5. Epigenetic Alterations What it is: Picture DNA as the permanent blueprint of the body; the epigenome acts as the switches that turn specific genes on or off based on our environment and lifestyle. As we age, the mechanisms controlling these switches begin to fail, preventing genes from operating as efficiently as they did in youth [3]. Why it matters for skin: Rather than just being a symptom of getting older, shifts in the epigenome actively drive the skin's aging process. Fortunately, scientists can map these genetic switches to evaluate exactly how well certain topical treatments work, allowing us to see if a product can genuinely decelerate aging within the cells [9]. Where does Sequential fit in? Today, consumers demand "healthspan" and "skin longevity" products that target root biological causes rather than acting as temporary cosmetic fixes [12]. Targeting complex issues like chronic inflammation and microbiome imbalance requires highly advanced, active formulations. More importantly, regulatory bodies and modern consumers require strict, physiological proof of efficacy. Testing these advanced claims in standard petri dishes or skin models fails to capture the full interconnected picture of how we age on a biological level. This is where Sequential Bio steps in. Sequential's multi-omic platform integrates multiple layers of biological data to provide a holistic view of a formula’s performance: SNP Detection: Maps a consumer's unique DNA to reveal their natural baseline for skin aging, such as their likelihood to develop wrinkles. It helps predict how a consumer will respond to specific ingredients. This takes the guesswork out of formulation, empowering you to create highly personalized, science-backed product lines that you know will work. Microbial Gene Expression: Uncover how genes are activated in response to treatments. This gives in depth- insight into how the skin's surface reacts to your formulation. Proteomics: Measures the complete protein profile (elastin, keratin and collagen) of the skin to track how product impacts the cellular function and structural integrity. This gives you definitive proof that your product rebuilds and maintains the skin’s structure. By shifting away from simple observational studies and toward deep-level multi-omic biological validation, Sequential's multi-omic platform validates what's happening at the molecular level, giving personal care and dermocosmetic brands proof of biological mechanism; not just efficacy, but clear, and actionable data. The future of longevity skincare isn't about concealing age; it’s about biological validation. The focus has shifted to the mechanism of action. Consumers want to know what is happening at a molecular level: what is your product actually doing beyond the surface? References Haykal, D. et al. (2025) 'Advances in longevity: The intersection of regenerative medicine and cosmetic dermatology', Journal of Cosmetic Dermatology. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC12268380/ (Accessed: 28 April 2026). Klinngam, W. et al. (2025) 'Longevity cosmeceuticals as the next frontier in cosmetic innovation: A scientific framework for substantiating product claims', Frontiers in Aging, 6. Available at: https://doi.org/10.3389/fragi.2025.1586999 (Accessed: 29 April 2026). López-Otín, C. et al. (2023) 'Hallmarks of aging: An expanding universe', Cell, 186(2), pp. 243-278. Available at: https://doi.org/10.1016/j.cell.2022.11.001 (Accessed: 29 April 2026). Gabriel, N. (2025) 'Inflammaging: How chronic inflammation accelerates visible aging', Ultimate Cosmetics. Available at: https://www.ultimatecosmetics.com.au/blog/inflammaging (Accessed: 28 April 2026). Borrego-Ruiz, A. and Borrego, J.J. (2024) 'Microbial dysbiosis in the skin microbiome and its psychological consequences', Microorganisms. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC11433878/ (Accessed: 28 April 2026). Challa, V. et al. (2025) 'Microbiome–aging–wrinkles axis of skin: Molecular insights and microbial interventions', International Journal of Molecular Sciences, 26(20), p. 10022. Available at: https://www.mdpi.com/1422-0067/26/20/10022 (Accessed: 28 April 2026). Lifespan.io (no date) Altered Intercellular Communication. Available at: https://lifespan.io/topic/altered-intercellular-communication/ (Accessed: 29 April 2026). Skin Organoids in Proteostasis Research: Early Insights into Aging (2025). Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC12961993/ (Accessed: 29 April 2026). Booth, L.N. and Brunet, A. (2016) 'The aging epigenome', Molecular Cell, 62(5), pp. 728-744. Available at: https://pubmed.ncbi.nlm.nih.gov/27259204/ (Accessed: 29 April 2026). Agrawal, R., Hu, A. and Bollag, W.B. (2023) 'The skin and inflamm-aging', Biology, 12(11), p. 1396. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC10669244/ (Accessed: 29 April 2026). Lancôme (2026) Lancôme Booklet. Available at: https://www.science.org/cms/asset/522c73c5-09e4-4279-96eb-8f764c08dc9c/_20260316_cpub_lancome_booklet.pdf (Accessed: 29 April 2026). Vogue (2026) 2026's biggest skincare trends to try now. Available at: https://www.vogue.com/article/2026s-biggest-skincare-trends-to-try-now (Accessed: 29 April 2026).

Tranexamic acid (TXA) has gained significant attention in skincare for its ability to treat hyperpigmentation by interrupting both pigment formation and pigment driven inflammation. Originally used medically to reduce bleeding, TXA inhibits plasma activity, a pathway recognised as relevant in pigment regulation. Its long clinical history means TXA enters cosmetic skincare with a stronger evidence base than many commonly used brightening ingredients. As its use grows, understanding how TXA performs within real formulations and on different skin types is essential for credible product development. What We Know: TXA (oral, intradermal and topical) improves melasma and other forms of hyperpigmentation, with significant reductions in MASI scores when compared to baseline or control (Calacattawi,et al, 2024). TXA decreases UV-induced melanocyte signalling, helping limit excess melanin production (Minasyan et al, 2024). TXA disrupts pigment transfer from melanocytes to keratinocytes, improving post-inflammatory hyperpigmentation (Chen et al, 2024). Topical TXA is well tolerated and can be paired with treatments such as microneedling, to enhance results, offering a safer alternative to stronger agents like hydroquinone (Konisky et al, 2023). Industry Impact and Potential: TXA’s multi-pathway action offers advantages for product development; Broad applicability -> Effective across varied pigmentation concerns including melasma, post inflammation hyperpigmentation and general uneven tone. Good tolerability -> Suitable for sensitive skin when formulated at low concentrations. Synergistic formulating -> Pairs well with niacinamide, vitamin C derivatives and retinoids for complementary pathways. Our Position: At Sequential, we help brands move from “TXA is trending” to “here is exactly what TXA is doing in this formula, on this skin.” We can help uncover what TXA is actually doing once it enters a full product system, how it interacts with other actives, whether it reaches relevant biological pathways, and how skin responds over time. Using our in-vivo testing frameworks, microbiome-aware models and multi-omic platforms, we can map changes in pigment biology, inflammation, and barrier behaviour . Our global database of 50,000+ samples allows us to benchmark TXA-containing formulations against diverse skin types, tones and real-world microbiome profiles, revealing who benefits most and why. References: Calacattawi, R. et al. (2024). Tranexamic acid for melasma: meta-analysis of RCTs. J Dermatol Treat, 35. Chen, T. et al. (2024). Tranexamic acid for hyperpigmentation disorders: an update. Clin Cosmet Investig Dermatol, 17, 2151–2163. Konisky, H. et al. (2023). Tranexamic acid in melasma: administration routes. J Cosmet Dermatol, 22, 1197–1206. Minasyan, M. et al. (2024). Oral tranexamic acid for PIH prevention and treatment. Dermatol Surg, 50, S219–S224.

Proteomics is the large-scale study of proteins, how they are expressed, modified and interact with the body. In skincare, proteomics is emerging as a powerful tool to understand how products influence skin function at a molecular level. Proteins play an important part in many skin processes and by analysing them, offers a more accurate picture of skin health, deeper than surface level observations alone. Unlike genomics, proteomics captures which proteins are present and active under specific conditions. What We Know: Proteomic analysis can identify shifts in structural proteins (e.g., keratin, filaggrin, collagen) associated with barrier strength and elasticity (Ma et al, 2020). Longitudinal proteomic monitoring reveals how products influence ageing pathways, including oxidative stress responses and collagen degradation (McCabe et al, 2020). Proteomics helps differentiate between short-term cosmetic effects and deeper, biologically meaningful changes (Benoit et al, 2023). Proteomics can be combined with microbiome data to show how protein changes relate to shifts in microbial activity, giving a clearer picture of overall skin health (Roux et al, 2021). Industry Impact and Potential: Proteomics opens new opportunities for product development; Targeted formulations:  By identifying protein level changes, more precise ingredient selection for specific skin concerns can occur. Personalised skincare:  Proteomic fingerprints may help tailor products to individual biological responses rather than general skin types. Credible product claims:  By combining proteomics with clinical endpoints, formulators can link specific protein changes directly to visible and functional outcomes. Our Position: At Sequential, we move beyond generic claims to generate clear, defensible evidence of biological impact. By integrating proteomic analysis with microbiome and multi-omic data from our global database of 50,000+ samples, we can determine exactly how formulations influence skin function over time. Our approach focuses on real-world evidence, quantifying changes in protein expression, barrier integrity and resilience, to support the development of products grounded in measurable outcomes rather than marketing terminology. References: Benoit, I. et al. (2023). A proteome-centric view of skin ageing and age-related pathways. Clin Cosmet Investig Dermatol, 16, 79–85. Ma, J. et al. (2020). Quantitative proteomics analysis of young and elderly skin. Aging (Albany NY), 12, 13529–13554. McCabe, M. et al. (2020). Alterations in extracellular matrix composition during ageing. Matrix Biology Plus, 8. Roux, P. et al. (2021). Integrative multi-omics reveals microbe–metabolite clusters linked to skin health. J Invest Dermatol.

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Partner with a specialist CRO for microbiome, genomic, and biomarker analysis. Support complex studies with integrated, high-quality data. Extend your clinical capabilities with microbiome & multi-omics expertise SKIN | SCALP | INTIMATE | ORAL We partner with CROs to provide advanced microbiome, genomic, and biomarker analysis—supporting complex study requirements without compromising timelines, quality, or client expectations. Extend your study capabilities A specialist partner, integrated into your workflow Sequential acts as an embedded scientific partner, supporting CROs with advanced biological analysis while allowing you to retain full ownership of client relationships. We provide: Microbiome sequencing and analysis Multi-omics and genomic profiling Biomarker-driven study design Condition-specific expertise in dermatology Our team integrates seamlessly into your study workflow, ensuring: aligned protocols consistent data quality efficient communication across stakeholders When study complexity exceeds internal capabilities As clinical studies evolve, sponsors increasingly require: microbiome analysis genomic and epigenetic profiling biomarker-driven endpoints For many CROs, these capabilities are: not available in-house difficult to build quickly or inefficient to scale for specific studies This creates risk: delays in study delivery reliance on fragmented external vendors challenges maintaining quality and consistency Multi-omics expertise on demand Access advanced capabilities without the need to build internal infrastructure. Seamless integration into your workflows We operate as an extension of your team, aligning with your protocols, timelines, and client requirements. Quality reproducible data & results Validated assays, SOP-controlled processes, and in-house analysis ensure consistent, reliable outputs. A collaborative, CRO-aligned approach 1 Study Protocols Integration We align with your study design, endpoints, and client requirements to ensure seamless integration. 2 Sampling & Assay Execution We support non-invasive sampling and run validated microbiome and multi-omics assays under controlled conditions. 3 In-house analysis & interpretation All data is processed internally, ensuring quality, speed, and scientific consistency. 4 Reporting & delivery We deliver clear, structured outputs that integrate directly into your study reports and client deliverables. Results Sequential Patch Results Multi-Omics Results Packages

Throughout the year, Sequential has the pleasure of going to various conferences and trade shows where we talk all things microbiome testing and clinical studies. Don't miss us when we're in your city next! Connect With Us At Conferences At Sequential, we believe in the power of personal connections and the exchange of ideas to foster innovation and growth. As we actively participate in various conferences and industry events, we invite you to be a part of these enriching experiences. Explore the opportunities to engage with our team, discover the latest industry trends, and strengthen the bonds that drive mutual success. Join us at conferences to connect, learn, and pave the way for future collaborations. Where we will be in 2026 2-4 March Cambridge, United Kingdom 18-19 March Copenhagen, Denmark 14-16 April Paris, France 19-20 May New York City, USA 14 July Liverpool, United Kingdom 28 September - 1 October Perth, Australia 10-11 November Coventry, United Kingdom Microbiome Interactions in Health and Disease Our CEO & Co-founder, Dr. Oliver Worsley, will have the pleasure of attending this year. Microbiome Times Partnering Forum We are incredibly excited to be part of this forum, where we get to discuss with experts in the industry. In-cosmetics Global Have the pleasure of exhibiting and presenting at In-cosmetics Global. Come visit us at Booth (1A64) and listen to our CEO & Co-founder, Dr. Oliver Worsley, speak on “Advancing Personal Care Claims with integrated Human and Microbiome Data” on 14th April, Theatre 3 – 15.05 - 15.35. NYSCC Supplier's Day We are back at New York Supplier’s Day! (Booth information TBA) SCS Conference We will be attending the SCS Conference and look forward to connecting with industry peers. IFSCC Congress We are pleased to be attending the IFSCC Congress, engaging with the global cosmetics science community. SCS Formulate Visit us at Booth (600) at this year’s SCS Formulate to learn more about our work and speak with the team. Connect with us on Socials!