Mechanisms of ageing

Recent experimental work from a variety of biological systems, ranging from yeast to human beings, lends increasing support to the view that stochasti c damage inflicted to biological macromolecules is the driving force for th e ageing process. The damage is derived from small reactive molecules, most prominently reactive oxygen intermediates (ROI), that arise during normal cellular metabolism and are associated with important if not essential cell ular functions. The major classes of macromolecules at risk are proteins, l ipids and DNA, but damage to DNA (both nuclear and mitochondrial) may entai l particularly severe consequences. Cellular dysfunction resulting from mac romolecular damage can be detected as a variety of expressions, such as gen omic instability, inappropriate cell differentiation events or cell death. While for post-mitotic cell types replacement of the dead cell by another c ell of the same lineage is not possible, mitotic cell types may initially r eplace dead cells via cell proliferation. But exhaustion of the self-renewa l capacity of the respective lineage, by either replication-associated or d amage-associated telomere shortening, will ultimately also lead to loss of parenchymal cell mass and functional impairment of tissues, the latter bein g a typical feature of ageing of tissues and organs. It has been demonstrat ed in various experimental systems that the rate ageing of can be retarded by lowering the production of endogenous ROI or by improving cellular anti- oxidative defences. Whether augmentation of cellular DNA repair capacity wi ll have the same effect remains to be seen.