Abstract
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.
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Abbreviations
- LVs:
-
Lymphatic vessels
- UV:
-
Ultraviolet
- LECs:
-
Lymphatic endothelial cells
- LMC:
-
Lymphatic muscle cell
- ECM:
-
Extracellular matrix
- NO:
-
Nitric oxide
- eNOS:
-
Endothelial NO synthase
- iNOS:
-
Inducible NO synthase
- CCBE1:
-
Calcium-binding EGF domain-1
- HAPLN1:
-
Hyaluronan and proteoglycan link protein 1
- ZO-1:
-
Zonula occludens protein 1
- Angptl6:
-
Angiopoietin-like protein 6
- YAP:
-
Yes-associated protein
- ROS:
-
Reactive oxygen species
- PROX-1:
-
Prospero-related homeobox protein 1
- SASP:
-
Senescence-associated secretory phenotype
- VEGF-C:
-
Vascular endothelial growth factor C
- VEGFR-3:
-
Vascular endothelial growth factor receptor 3
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This study was supported by National Natural Science Foundation of China (81872512), Shanghai Rising-Star Program (20QA1408600), the Fundamental Research Funds for the Central Universities (22120220641).
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YY, XW, and PW had the idea for the article. YY reviewed the literature and drafted the paper. XW and PW critically revised the work, and they contributed equally to this work and should be considered co-corresponding authors. All authors read and approved the final manuscript.
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Yang, Y., Wang, X. & Wang, P. Signaling mechanisms underlying lymphatic vessel dysfunction in skin aging and possible anti-aging strategies. Biogerontology 24, 727–740 (2023). https://doi.org/10.1007/s10522-023-10016-3
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DOI: https://doi.org/10.1007/s10522-023-10016-3