[The mechanisms of aging. From genetic to epigenetic]

HUNDREDS OF THEORIES: The mechanisms of aging have been intensively studied since the middle of the last century on cellular and molecular level in experimental studies, case reports and epidemiological estimations. They have also generated a number of speculations and over 300 theories. THE ROLE OF GENES: Genetic data suggest an indirect determinism through the enhancement of antiradical defense mechanisms or by the presence of genes enhancing age-related diseases. One of the best examples is the dose-effect of genes coding for apolipoprotein E(4) (epsilon (4)), its presence in 0, 1 or 2 copies proportionally increases the risk of Alzheimer-type dementia but also atherosclerotic diseases. THE UNFORESEABILITY OF NATURE: However, it appears more and more clearly that epigenetic mechanisms (escaping direct genetic control) would be more directly implied in the decline of physiological functions with age. Several examples of such mechanisms are discussed and may be attributed to "negligence of nature' during the development of multicellular eukaryotic organisms. However, their very nature makes it possible to propose specific therapeutic interventions in order to slow down the effects of such mechanisms indirectly coded in the genome.