A note on 'aging-pharmacodynamics' with application to the analysis of the age-dynamics of adipocyte response to epinephrine and insulin.

This note aims at clearing some semantic problems in the literature concerning the analysis of the effect of age on dose-response curves as well as standardize the way such data should be presented. In particular it is shown how to assess the age-dynamics (i.e. the pattern of change as a mathematical function of age) of the sensitivity of a receptor system to a given agent, of the quantitative overall changes of the cellular response apparatus which affect response capacity, and of the interaction between different simultaneously acting agents. The concepts and theory are illustrated using as an example the in vitro isolated rat fat cell (or adipocyte) which we have recently studied extensively with regards to the age-dynamics of its lipolytic response to epinephrine and insulin. This 'aging-pharmacodynamics' analysis has led to the surprising conclusion of a rebound effect of age (decrease at maturity followed by increase at old age) on the sensitivity of the fat cell to epinephrine and to its antagonist (with respect to lipolysis) insulin, as well as a negative correlation of these sensitivities with fat cell size.