Ageing Processes in Collagens from Different Tissues of Rats

Abstract

At the beginning of my talk I would like to go back to 1973 and to recall the closing speech of Dr. Gardell at the Varberg Symposium on connective tissue ageing. At this opportunity, Dr. Gardell stressed the fact that among people who are involved in connective tissue ageing most of them are limited to the main protein component e.g., collagen and most of these people do not recognize the existence of cells in connective tissue. Although I am not going to speak very much about cells, I still recognize their existence and you perhaps would excuse my talking about extracellular proteins as these seem to play a very specific role in ageing processes. The nature of the connective tissue research has rapidly changed since the elucidation of the primary structure of the α_l polypeptide chain of collagen and since the elucidation of the nature of the major cross-links which for long have been believed to be to the main element in ageing of the extracellular protein components. I would like to stress that our picture of ageing connective tissue is that which has been formulated in 1972 by F.M. Sinex (1). In this view ageing of the connective tissue starts with the fact that the fibroblasts gradually lose their capability for metabolic activity and mitosis with age. Given the stimulation however, fibroblasts will proliferate in older animals, although not always in the most orderly or constructive way. As older tissue becomes more dormant the cross-linkage is completed and glycosaminoglycans perhaps will decrease or will themselves become aggregated. The fibrous protein which remains may either deteriorate, or become tougher depending on its environment. It is believed, though it is certainly not proved, that these changes may play an important role in transport processes and in the ability of cells to survive. This view is based on the fact that these changes in intercellular matrix may cause substantial changes in the microenvironment in which every cell has to live and to carry out the basic processes which allow this cell to survive. In addition to a general statement about an increase in cross-links with age, proposed some decades ago by Verzar (2) and followed by a number of investigators in the past years, we know nowadays that the formation of cross-links in connective tissue proteins is a very specific enzyme controlled process. We also know that the so-called unusual cross-links which are of other nature than those lysine derived are perhaps very rare if not absent at all.