Looking older - Fibroblast collapse and therapeutic implications
Looking older - Fibroblast collapse and therapeutic implications
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DOI：
10.1001/archderm.144.5.666
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发表时间：
2008-05-01
影响因子：
--
通讯作者：
Voorhees, John J.
中科院分区：
文献类型：
--
作者：
Fisher, Gary J.;Varani, James;Voorhees, John J.
皮肤外观是年龄的主要指标。在过去的十年中，在了解人类皮肤衰老的潜在机制方面取得了实质性进展。这种理解为抗衰老治疗的当前使用和新开发提供了基础。我们的目标是回顾目前有关皮肤衰老机制的最新知识，特别关注真皮胶原蛋白基质。老化皮肤的一个主要特征是真皮胶原蛋白基质的破碎。特定酶（基质金属蛋白酶）的作用会导致断裂，并损害真皮的结构完整性。产生和组织胶原蛋白基质的成纤维细胞不能附着到碎片胶原蛋白上。失去附着会阻止成纤维细胞从其支持物接收机械信息，并且它们会崩溃。拉伸对于胶原蛋白和胶原蛋白降解酶的正常平衡生产至关重要。在老化的皮肤中，塌陷的成纤维细胞产生低水平的胶原蛋白和高水平的胶原蛋白降解酶。这种不平衡会导致衰老过程陷入自我延续、永无休止的有害循环中。经临床证明的抗衰老治疗，如局部视黄酸、二氧化碳激光换肤和皮内注射交联透明质酸，可刺激新的、未受损的胶原蛋白的产生。成纤维细胞附着在这种新的胶原蛋白上可以产生拉伸，从而平衡胶原蛋白的产生和降解，从而减缓衰老过程。胶原蛋白碎片导致老化人类皮肤结构完整性丧失和成纤维细胞功能受损。刺激新的、无碎片的胶原蛋白产生的治疗应该可以显着改善老化皮肤的外观和健康。
Skin appearance is a primary indicator of age. During the last decade, substantial progress has been made toward understanding underlying mechanisms of human skin aging. This understanding provides the basis for current use and new development of antiaging treatments. Our objective is to review present state-of-the-art knowledge pertaining to mechanisms involved in skin aging, with specific focus on the dermal collagen matrix. A major feature of aged skin is fragmentation of the dermal collagen matrix. Fragmentation results from actions of specific enzymes (matrix metalloproteinases) and impairs the structural integrity of the dermis. Fibroblasts that produce and organize the collagen matrix cannot attach to fragmented collagen. Loss of attachment prevents fibroblasts from receiving mechanical information from their support, and they collapse. Stretch is critical for normal balanced production of collagen and collagen-degrading enzymes. In aged skin, collapsed fibroblasts produce low levels of collagen and high levels of collagen-degrading enzymes. This imbalance advances the aging process in a self-perpetuating, never-ending deleterious cycle. Clinically proven antiaging treatments such as topical retinoic acid, carbon dioxide laser resurfacing, and intradermal injection of cross-linked hyaluronic acid stimulate production of new, undamaged collagen. Attachment of fibroblasts to this new collagen allows stretch, which in turn balances collagen production and degradation and thereby slows the aging process. Collagen fragmentation is responsible for loss of structural integrity and impairment of fibroblast function in aged human skin. Treatments that stimulate production of new, nonfragmented collagen should provide substantial improvement to the appearance and health of aged skin.