Use of mathematical models of survivorship in the study of biomarkers of aging: the role of heterogeneity

An ever increasing number of people have been engaging in aging research us ing various interventions aimed to modify aging processes, and/or life span , of experimental animals. Since this type of studies needs outcome paramet ers for assessing the efficacy of such interventions. research on biomarker s of aging (ABs) has received new stimuli. In the present paper. the proble m of the occurrence of a vicious circle any time we study ABs and determina nts of aging is addressed. In fact, while ABs would represent the standard reference to be used in the Study of the main causes of processes of aging, these very determinants should already be known in order to get reliable A Bs. A feasible way to overcome this impasse is proposed, using mathematical models of survivorship or mortality based on biological hypotheses and acc ounting for inter-individual heterogeneity, a necessary ingredient for a co rrect interpretation of survival results. Specific kinetics of experimental parameters that are candidates as ABs can be compared to the kinetics hypo thesized for general biological functions entering the model. We have built a model of this type that can also be used to perform a reliable overall g ross estimate of the rate of aging, R-a, in the population. a parameter use ful when judging the success of interventions aimed to act on determinants or aging. The perspective that theory of complex systems can be of help in the search for ABs is also discussed. (C) 2001 Elsevier Science Ireland Ltd . All rights reserved.