To translate pharmacogenetics in geriatrics: towards a personalized medicine

Geriatric wards represented a very interesting clinical setting in which an increased drugs use rise the prevalence of adverse drug reactions (ADRs) and therapeutic failures (TFs). These are not independent phenomena, but the severe counterposed manifestations of a continuum of phenotypes in which the better drug response is the midpoint. Age-related changes in the regulation of cytochrome P450 (CYP) genes, encoding the most common drugmetabolizing enzymes, might be responsible of the observed age-associated drift towards ADRs and TFs. In this review article, a complete impression of the CYP pharmacogenetics and epigenetics is reported in the context of increasing age, in which epigenetic CYP-gene regulation might change. Physiological age-related changes in DNA-methylation, the main epigenetic mechanisms regulating gene expression in humans, results in a physiological decrease in CYP gene expression with advancing age. This may be one of the physiological changes that, together with an increased drug use, contributed to raise the prevalence of severe responder phenotypes in older age.