Genetic instability and aging: theories, facts, and future perspectives

The fundamental mechanisms involved in the physiological deterioration observed with age in mammalian organisms have not yet been elucidated. It appears that random alterations in informational biomolecules and in their synthesis could be the basis of such physiological changes. There is, however, a lack of knowledge with respect to the frequency and characteristics of changes introduced in the cellular molecular machinery. Moreover, the driving force initiating the generation of such alterations and the order of events in which they occur are unknown at present. In this article, data concerning the hypothesis that the aging process is associated with widespread genetic instability are reviewed in the context of the complex interactions between the three major informational biomolecules, DNA, RNA, and protein. We conclude that the results obtained to date do not rule out the possibility that genetic instability in a wide sense is a major causal factor in a number of age-related phenomena. However, it appears that new strategies based on a new technology are ultimately necessary to elucidate the alterations in the intricately interwoven patterns of molecular control that could underlie the various aspects of the aging process. A first attempt is made to formulate the problems in this field and to provide some solutions.