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PEPTIDES 49


Novel senopreventive peptide for skin ageing


Shaohua Wang, Meijie Wang, Lun Yu - Metanovas Biotech


Skin ageing, driven by intrinsic and extrinsic factors, is a complex biological process resulting in a gradual decline in the skin’s structural and regenerative capacities. Intrinsic ageing is influenced by genetic, hormonal, and cellular changes, while extrinsic ageing is primarily driven by environmental stressors such as UV radiation, pollution, and inflammation.1,2 A key cellular event that contributes to


both intrinsic and extrinsic ageing is cellular senescence, a state of irreversible growth arrest induced by stressors like DNA damage, oxidative stress, and inflammation.3 Senescent cells accumulate with age and


contribute to tissue dysfunction through the secretion of a variety of molecules, collectively referred to as the senescence-associated secretory phenotype (SASP).4


ABSTRACT


Skin ageing is a multifactorial process driven by both intrinsic and extrinsic factors, which manifests as wrinkles, age spots, dryness, thinning, and a loss of elasticity. Cellular senescence plays a pivotal role in ageing, characterized by the senescence-associated secretory phenotype (SASP), which includes the secretion of pro-inflammatory cytokines, matrix metalloproteinases, and reactive oxygen species (ROS). In this study,


we explored the potential of MetaTlr, an AI-designed peptide, as a senopreventive


The SASP consists


of inflammatory cytokines, chemokines, reactive oxygen species (ROS) and extracellular matrix (ECM)-modifying enzymes, which contribute to skin ageing by promoting tissue dysfunction, oxidant stress, inflammation, and the degradation of ECM.5 The accumulation of senescent cells in the skin,


particularly in response to UV-induced damage, oxidative stress, and chronic inflammation, is thought to accelerate the visible signs of ageing, including wrinkles, loss of elasticity, and pigmentation changes.6


In response to these


challenges, there has been growing interest in developing senotherapeutics—compounds that target senescent cells or modulate the SASP to mitigate age-related skin changes.7


Senolytic


agents selectively induce the death of senescent cells, while senomorphic agents aim to suppress the harmful effects of the SASP without inducing cell death. A third, complementary approach, senoprevention, instead aims to keep stressed cells from entering senescence in the first place.8 A variety of peptides have been applied to


cosmetics for anti-skin ageing, based on their high biocompatibility and safety, as well as multi- dimensional efficacy.9


an AI-designed peptide, demonstrated promise in modulating key pathways involved in skin ageing. By targeting inflammation and oxidative stress, two major contributors to cellular senescence, the senopreventive peptide presents a novel strategy for addressing skin ageing and related conditions.


Methods Cell culture and reagents Human keratinocytes (HaCaT), human foreskin


www.personalcaremagazine.com The senopreventive peptide,


Anti-oxidant test The ABTS radical cation (ABTS+


oxidizing ABTS with potassium persulfate (K2


·) was generated by S2


O8 ),


resulting in a distinct blue-green coloration with increased absorbance at 734 nm. Antioxidant activity was quantified by monitoring the reduction in absorbance after sample addition. Hydroxyl radicals (·OH), generated via the /H2


Fenton reaction (Fe2+ O2 system), degraded


rhodamine B, decreasing its characteristic purple- red absorbance at 550 nm. The scavenging rate was determined by comparing absorbance changes before and after sample treatment. HaCaT cells were exposed to tert-butyl


hydroperoxide (TBHP, 160 µM) to induce ROS production. Upon ROS interaction, fluorescent probe DCFH-DA (10 μM) would be oxidized to fluorescent DCF. Fluorescence intensity (excitation/ emission: 488/525 nm), quantified by fluorescence microscopy, reflected the ROS level.


fibroblast HFF-1, P815 mast cells, and THP-1 macrophages (purchased from Immocell) were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin. SH-SY5Y neuroblastoma cells (purchased from Immocell) were cultured with 2 mM L-glutamine. All cells were maintained in a humidified incubator at 37°C with 5% CO2


. The senopreventive


peptide was synthesized by GenScript Biotech (Nanjing, China) using Fmoc solid-phase peptide synthesis technology with a purity of > 95%.


agent targeting cellular senescence with both senomorphic and senolytic effects. The senopreventive peptide exhibited significant antioxidant properties, including the ability to scavenge ABTS and hydroxyl radicals. Furthermore, in vitro studies demonstrated that the senopreventive peptide effectively inhibited the secretion of pro-inflammatory cytokines such as IL-6 and IL-1β across multiple cell types, including THP-1 macrophages, P815 mast cells, and HaCat/SH-SY5Y co-culture cells. Finally, the senopreventive peptide showed potential in mitigating intrinsic ageing by limiting the accumulation of senescent cells and alleviating UV-induced photoageing by inhibiting the degradation of collagen and Lamin B1. Additionally, the peptide also modulated key signaling pathways like TLR2 and NF-κB, which are central to the inflammatory response and anti-ageing. These findings suggest that the senopreventive peptide may represent a promising novel approach in combatting skin ageing by addressing inflammation and oxidative stress


Anti-inflammation assay THP-1 monocytes were stimulated with lipopolysaccharide (LPS, 1 µg/mL) for 24 h. Culture supernatants were collected, and IL-6/IL-1β levels were analysed using ELISA kits. Dexamethasone (10 µM) served as the positive control. P815 mast cells were treated with substance


P (SP, 100 nM) to trigger degranulation. IL-6/IL- 1Symbol levels were measured for inflammation, and β-Hexosaminidase (β-Hex) activity was measured as a degranulation marker (Coibo Biotech kit). Sodium cromoglicate (SC, 50 µM) was the reference inhibitor.


September 2026 PERSONAL CARE MAGAZINE


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