An original approach to aging: an appreciation of Fritz Verzár's contribution in the light of the last 50 years of gerontological facts and thinking.

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.