Robert L
Centre de Recherche Bioclinique sur le Vieillissement, Groupe Hospitalier Charles Foix-Jean Rostand, Ivry-sur-Seine, et Laboratoire de Recherche Ophthalmologique, Hôtel-Dieu, Paris, France.
Gerontology. 1998;44(6):307-17. doi: 10.1159/000022034.
Aging of connective tissues is important for the understanding of aging mechanisms of tissues rich in extracellular matrix and of age-dependent diseases often affecting such tissues. Aging mechanisms of such tissues can be divided as follows: (1) age-dependent modifications of matrix biosynthesis; (2) postsynthetic modifications of extracellular matrix, and (3) modifications of cell-matrix interactions. Examples are discussed for all three aspects of tissue aging, with special emphasis on the role of epigenetic reactions. These reactions include the Maillard reaction, uncontrolled proteolytic degradation, and free radical release. Proteolytic fragments of fibronectin and of elastic fibers were shown to produce noxious effects and to be engaged in vicious circles of autoentertained and self-amplified mechanisms. We studied in particular the role of the elastin-laminin receptor in tissue aging and in atherogenesis. The presence of saturating concentrations of elastin peptides in the circulation results in a chronic overstimulation of the receptor with sustained free radical and lytic enzyme production. Other examples of age-dependent uncoupling of receptors also illustrate the importance of altered receptor function in tissue aging and related pathologies.
结缔组织的老化对于理解富含细胞外基质的组织的老化机制以及常影响此类组织的年龄依赖性疾病至关重要。此类组织的老化机制可分为以下几类：（1）基质生物合成的年龄依赖性修饰；（2）细胞外基质的合成后修饰；以及（3）细胞 - 基质相互作用的修饰。文中讨论了组织老化所有这三个方面的例子，特别强调了表观遗传反应的作用。这些反应包括美拉德反应、不受控制的蛋白水解降解和自由基释放。已表明纤连蛋白和弹性纤维的蛋白水解片段会产生有害影响，并参与自我维持和自我放大机制的恶性循环。我们特别研究了弹性蛋白 - 层粘连蛋白受体在组织老化和动脉粥样硬化形成中的作用。循环中存在饱和浓度的弹性蛋白肽会导致受体的慢性过度刺激，并持续产生自由基和裂解酶。受体的年龄依赖性解偶联的其他例子也说明了受体功能改变在组织老化和相关病理学中的重要性。
