Wipro Skin Research and Innovation Centre, No. 7, Persiaran Subang Permai, Taman Perindustrian Subang, 47610, Subang Jaya, Selangor, Malaysia.
Department of Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
Br J Dermatol. 2017 Jan;176(1):159-167. doi: 10.1111/bjd.14832. Epub 2016 Dec 22.
Glycation is a nonenzymatic reaction that cross-links a sugar molecule and protein macromolecule to form advanced glycation products (AGEs) that are associated with various age-related disorders; thus glycation plays an important role in skin chronological ageing.
To develop a novel in vitro skin glycation model as a screening tool for topical formulations with antiglycation properties and to further characterize, at the molecular level, the glycation stress-driven skin ageing mechanism.
The glycation model was developed using human reconstituted full-thickness skin; the presence of N -(carboxymethyl) lysine (CML) was used as evidence of the degree of glycation. Topical application of emulsion containing a well-known antiglycation compound (aminoguanidine) was used to verify the sensitivity and robustness of the model. Cytokine immunoassay, quantitative real-time polymerase chain reaction and histological analysis were further implemented to characterize the molecular mechanisms of skin ageing in the skin glycation model.
Transcriptomic and cytokine profiling analyses in the skin glycation model demonstrated multiple biological changes, including extracellular matrix catabolism, skin barrier function impairment, oxidative stress and subsequently the inflammatory response. Darkness and yellowness of skin tone observed in the in vitro skin glycation model correlated well with the degree of glycation stress.
The newly developed skin glycation model in this study has provided a new technological dimension in screening antiglycation properties of topical pharmaceutical or cosmeceutical formulations. This study concomitantly provides insights into skin ageing mechanisms driven by glycation stress, which could be useful in formulating skin antiageing therapy in future studies.
糖基化是一种非酶促反应，它使糖分子和蛋白质大分子交联，形成与各种与年龄相关的疾病相关的晚期糖基化终产物（AGEs）；因此，糖基化在皮肤的自然老化中起着重要作用。
开发一种新的体外皮肤糖基化模型，作为具有抗糖基化特性的局部制剂的筛选工具，并进一步在分子水平上表征糖基化应激驱动的皮肤衰老机制。
使用人重建全厚皮肤建立糖基化模型；使用 N -（羧甲基）赖氨酸（CML）的存在作为糖基化程度的证据。局部应用含有已知抗糖基化化合物（氨基胍）的乳剂来验证模型的灵敏度和稳健性。进一步实施细胞因子免疫测定、定量实时聚合酶链反应和组织学分析，以表征皮肤糖基化模型中的皮肤衰老分子机制。
皮肤糖基化模型中的转录组和细胞因子谱分析显示出多种生物学变化，包括细胞外基质的分解代谢、皮肤屏障功能受损、氧化应激以及随后的炎症反应。体外皮肤糖基化模型中观察到的肤色变暗和变黄与糖基化应激程度密切相关。
本研究中新开发的皮肤糖基化模型为筛选局部药物或化妆品制剂的抗糖基化特性提供了新的技术维度。本研究同时提供了糖基化应激驱动的皮肤衰老机制的见解，这在未来的研究中可能对制定皮肤抗衰老疗法有用。
