Robert Ladislas
Laboratoire de Recherche Ophtalmologique, Hôtel-Dieu, Université Paris 5, Paris, France.
Gerontology. 2006;52(5):268-74. doi: 10.1159/000094607.
The motivation of this review is the 120th anniversary of the birth of Fritz Verzár, founder of experimental gerontology. His major contributions to aging research are shortly reviewed and re-evaluated in the light of modern gerontological research. Verzár undertook aging research after his retirement from the Chair of Physiology at the Medical Faculty of Basel. His first experiments on aging of the rat tail tendon revealed an important mechanism of aging: an exponential increase of cross-linking of collagen fibres. This observation, correctly interpreted by Verzár as a new age-dependent mechanism, was shown later to be attributed to the Maillard reaction, the non-enzymatic glycosylation of protein (and nucleotide bases) amino groups followed by evolution of the reaction to advanced glycation end products (AGEs) involved in a number of harmful reactions. Many of these reactions were shown to be mediated by receptors recognizing AGE products (RAGEs). This was the first example of a post-synthetic (post-translational) reaction involved in the aging of biological macromolecules, especially those of the extracellular matrix. Verzár extended the research activity of his team to several other aspects of aging research, such as loss of muscular strength, nutritional requirements at high altitude, cell loss with aging, and ultrastructural studies, and started also the first longitudinal clinical study of aging in a Basel population. Modern gerontological research confirmed and extended Verzár's observations. His work on collagen cross-linking by glycation became of paramount importance in recent times because of the rapid increase of diabetes type II, combined with the metabolic syndrome, one of the major pathologies of modern times.
本综述的缘起是实验老年学创始人弗里茨·韦扎尔诞辰120周年。我们根据现代老年学研究，简要回顾并重新评估了他对衰老研究的主要贡献。韦扎尔从巴塞尔医学院生理学系主任职位退休后，便投身于衰老研究。他对大鼠尾腱衰老进行的首批实验揭示了衰老的一个重要机制：胶原纤维交联呈指数增长。韦扎尔正确地将这一观察结果解读为一种新的年龄依赖性机制，后来发现这一机制归因于美拉德反应，即蛋白质（和核苷酸碱基）氨基的非酶糖基化，随后反应演变为晚期糖基化终产物（AGEs），涉及许多有害反应。许多这类反应被证明是由识别AGE产物的受体（RAGEs）介导的。这是生物大分子尤其是细胞外基质大分子衰老过程中涉及的合成后（翻译后）反应的首个实例。韦扎尔将其团队的研究活动扩展到衰老研究的其他几个方面，如肌肉力量丧失、高原营养需求、细胞衰老损失以及超微结构研究，还启动了巴塞尔人群中首个衰老纵向临床研究。现代老年学研究证实并扩展了韦扎尔的观察结果。由于II型糖尿病与代谢综合征（现代主要病症之一）的迅速增加，他关于糖基化导致胶原交联的研究在近期变得至关重要。
