Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
Biogerontology. 2023 Oct;24(5):727-740. doi: 10.1007/s10522-023-10016-3. Epub 2023 Jan 21.
Aging-related skin diseases are gradually increasing due to the imbalance of cutaneous homeostasis in the aging population. Skin aging-induced inflammation promotes systemic inflammation and may lead to whole-body aging. Lymphatic vessels play an important role in maintaining fluid and homeostasis balance. In intrinsically aged skin, the number of lymphatic vessels decrease and their functions decline, which is related to the reduced adhesion junctions between lymphatic endothelial cells, particularly VE-cadherin. VEGFC/VEGFR-3 signal pathway plays an important role in remodeling and expansion of lymphatic vessels; the downregulation of this pathway contributes to the dysfunction of lymphatic vessels. Meanwhile, we proposed some additional mechanisms. Decline of the pumping activity of lymphatic vessels might be related to age-related changes in extracellular matrix, ROS increase, and eNOS/iNOS disturbances. In extrinsically aged skin, the hyperpermeability of lymphatic vessels results from a decrease in endothelial-specific tight junction molecules, upregulation of VEGF-A, and downregulation of the VEGFC/VEGFR-3 signaling pathway. Furthermore, some of the Phyto therapeutics could attenuate skin aging by modulating the lymphatic vessels. This review summarized the lymphatic vessel dysfunction in skin aging and anti-aging strategies based on lymphatic vessel modulation.
随着老龄化人口中皮肤内稳态失衡，与衰老相关的皮肤疾病逐渐增多。皮肤衰老引起的炎症会促进全身炎症，可能导致全身性衰老。淋巴管在维持液体和内稳态平衡方面起着重要作用。在内在老化的皮肤中，淋巴管数量减少，其功能下降，这与淋巴管内皮细胞之间的黏附连接减少有关，特别是 VE-钙黏蛋白。VEGFC/VEGFR-3 信号通路在淋巴管的重塑和扩张中起着重要作用；该通路的下调导致淋巴管功能障碍。同时，我们提出了一些其他的机制。淋巴管的抽吸活性下降可能与细胞外基质的年龄相关变化、ROS 增加和 eNOS/iNOS 紊乱有关。在外在老化的皮肤中，淋巴管的高通透性是由于内皮特异性紧密连接分子减少、VEGF-A 上调和 VEGFC/VEGFR-3 信号通路下调所致。此外，一些植物疗法可以通过调节淋巴管来减轻皮肤衰老。本综述总结了皮肤衰老过程中淋巴管功能障碍和基于淋巴管调节的抗衰老策略。
