The role of glucocorticoids in aging and age-related pharmacotherapy.

Recently we have evaluated the role of glucocorticoids (GC) and other stress hormones in the pathogeny of age-related diseases. In order to perform this evaluation, we considered the DOHaD paradigm discussing long-term effects of adverse perinatal factors. In the present work, a part of the data collected previously was used for analyzing the role of GC in aging, as well as in age-related pharmacotherapy. The data were gathered in various databases, preferably in English, during the last 25-30 years. Although some authors suggest that GC can be considered as hormones of aging, the majority of investigators are quite careful in this respect. Nevertheless, it appears that the role of GC in various stages of ontogeny and transitions between them is well established. Besides, there are a lot of data that confirm a contribution of GC to the phenomena of perinatal programming/imprinting of adult diseases. What for the relationship between GC and aging, some studies confirm its existence, at least partially. Having analyzed the dynamics of morbidity and mortality of age-related diseases, we concluded on the absence of evidence in favor of unique general scheme of aging, where GC could play a role. However, in a rather paradoxal mode it was demonstrated that GC participate, at least indirectly, in the mechanisms of action of various drugs used for the treatment of cardiometabolic disorders (beta-blockers, angiotensin antagonists, some oral hypoglycemic agents) and neuropsychiatric diseases (antidepressants, antipsychotic agents, benzodiazepines and some anticonvulsive medicines), as well as in the effects of toxic agents (for example, drugs of abuse, including caffeine). Using the concept of hormesis, we discuss a reason for frequent utilization of these drugs, and not GC or their antagonists, in age-related pharmacotherapy. The caution is suggested in considering the essential function of GC in aging. Nevertheless, due to existence of theory that connects GC with aging via the mechanisms of allostasis, we are planning to elaborate a more detailed model that might include, besides GC, also some other hormones, cytokines, etc., as well as their interactions. It is stressed that the interactions of GC with other bioregulators should be reevaluated in a chronobiological mode, in order to strengthen the bases of chronopharmacotherapy. One of the principal challenges is the prevention of adverse effects of pharmacotherapy in long-term. In this sense, DOHaD paradigm has opened the discussion of possibility for pharmacotoxicologic programming / imprinting, an important question attracting the attention of researchers.