52 PEPTIDES A MetaTLR C


Toll-like receptor 2 (TLR2) protein


Binding free energy = -55.837 kcal/mol B 150 Kd = 0.543 µM 100 50 0 -50 0 50 Times (s)


Figure 4: The senopreventive peptide binds to TLR2 protein and blocks NF-κB pathways. (A) Molecular dynamics simulation revealed strong binding between the senopreventive peptide and TLR2. (B) SPR analysis demonstrating a high-affinity interaction between the senopreventive peptide and TLR2. (C) Fluorescence data statistics of NF-κB reporter cell after LPS stimulation. (D) Fluorescence image of NF-κB reporter cell after LPS stimulation


Moreover, treatment with the senopreventive peptide significantly reduced the proportion of SA-β-gal-positive cells. These findings suggest that the senopreventive peptide may protect against UV-induced photoaging.


The senopreventive peptide binds to TLR2 protein and blocks NF-κB pathways To elucidate the mechanistic basis of the senopreventive peptide, we initially sought to identify its molecular targets. Molecular dynamics simulation revealed strong binding between the senopreventive peptide and TLR2, with a calculated binding free energy of -55.837 kcal/ mol, predominantly mediated by hydrogen bond interactions. This computational prediction was experimentally validated through SPR analysis, demonstrating a micromolar-affinity interaction between the senopreventive peptide and TLR2 protein with a dissociation constant (Kd) of 0.543 µM.


This indicates that the senopreventive peptide


binds efficiently to TLR2 and may exert its anti- inflammatory activity by modulating TLR2 activity. We further investigated NF-kB activity, which acts downstream of multiple toll-like receptors and is a pivotal regulator of inflammation. As shown in Figure 4, LPS stimulation


significantly enhanced the expression of dsRED driven by NF-κB response elements in THP-1 reporter cells, while the senopreventive peptide treatment markedly suppressed this induction. Importantly, the expression of GFP under the


constitutive UBC promoter remained consistent across experimental groups, confirming equivalent loading conditions. . These results collectively demonstrate that the Senopreventive Peptide indeed modulates NF-κB signaling, with TLR2 identified as a candidate upstream target.


PERSONAL CARE MAGAZINE September 2026


Conclusion The findings of this study demonstrate that the senopreventive peptide, an AI-designed peptide, exhibits significant senopreventive, anti-inflammatory and antioxidant properties by targeting two critical drivers of cellular senescence: inflammation and oxidative stress. The peptide’s ability to scavenge free radicals,


inhibit pro-inflammatory cytokine secretion, and modulate key signaling pathways such as TLR2 and NF-κB underscores its potential as a novel cosmetic active for managing the visible signs of ageing. NF-κB drives pro-inflammatory gene activation,


inflammatory T-cell regulation, and senescence- associated secretory phenotype (SASP), linking it to skin inflammation, ageing, and oxidative stress. It exacerbates oxidative damage by suppressing Nrf2 activity.11


14:1195272


2. Csekes E, Račková L. Skin Aging, Cellular Senescence and Natural Polyphenols. International Journal of Molecular Sciences. 2021 Nov;22(23):12641


3. Franco AC, Aveleira C, Cavadas C. Skin senescence: mechanisms and impact on whole- body aging. Trends in Molecular Medicine. 2022 Feb;28(2):97-109


4. Ho CY, Dreesen O. Faces of cellular senescence in skin aging. Mechanisms of Ageing and Development. 2021; 198:111525


5. Thau H, Gerjol BP, Hahn K et al. Senescence as a molecular target in skin aging and disease. Ageing Research Reviews. 2025; 105:102686


The senopreventive peptide, a dual-action


compound, inhibits NF-κB signaling—reducing inflammation and indirectly mitigating oxidative stress—while directly scavenging free radicals and limiting the accumulation of senescent cells. This dual mechanism positions the senopreventive peptide as a senopreventive agent with potential to delay skin ageing by targeting both intrinsic (e.g. oxidative stress) and extrinsic (e.g. UV-induced damage) factors. Topical application of this peptide may synergize


with existing senotherapeutics to enhance anti- ageing efficacy. Further research should explore its combinatorial effects and optimal delivery systems. By addressing inflammation, oxidative stress, and the onset of cellular senescence, the senopreventive peptide represents a novel, non-invasive skin care strategy for skin health and ageing.


References 1. Shin SH, Lee YH, Rho N-K, Park KY. Skin aging from mechanisms to interventions: focusing on dermal aging. Frontiers in Physiology. 2023 May;


6. Fitsiou E, Pulido T, Campisi J et al. Cellular Senescence and the Senescence- Associated Secretory Phenotype as Drivers of Skin Photoaging. Journal of Investigative Dermatology. 2021;141(4):1119-1126


7. Thompson EL, Pitcher LE, Niedernhofer LJ, Robbins PD. Targeting Cellular Senescence with Senotherapeutics: Development of New Approaches for Skin Care. Plastic and Reconstructive Surgery. 2022 Oct;150,12S-19S


8. Wyles SP, Carruthers JD, Dashti P, Yu G, Yap JQ, Gingery A, Tchkonia T, Kirkland JL. Cellular Senescence in Human Skin Aging: Leveraging Senotherapeutics. Gerontology. 2024;70(1):7-14


9. Schagen SK. Topical Peptide Treatments with Effective Anti-Aging Results. Cosmetics. 2017;4(2):16


PCM


10. Wilson AA, Kwok LW, Porter EL et al. Lentiviral Delivery of RNAi for In Vivo Lineage-Specific Modulation of Gene Expression in Mouse Lung Macrophages. Molecular Therapy. 2013;21(4):825-833


11. Wang Y, Wang L, Wen X et al. NF-κB signaling in skin aging. Mechanisms of Ageing and Development. 2019; 184:111160


www.personalcaremagazine.com 100 150 GFP (Green)


■ 62.5 nM ■ 125 nM ■ 250 nM ■ 500 nM ■ 1000 nM ■ 2000 nM ■ 0 nM


D NFkB (Red) Normal


18000 12000 6000 0


10000 * 5000 *** ** 0 Normal LPS


DEX MetaTlr (50 µg/mL)


LPS (0.1 µg/mL) Normal LPS


DEX MetaTIr (50 µg/mL)


LPS (0.1 µg/mL) ***


LPS


LPS+DEX


LPS+MetaTlr


Response (RU)


NFκB in THP-1 (A558


nm)


GFP in THP-1 (A488


nm)


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