Functional interrelationships in aging processes: alterations and reversibility

Abstract

The problem of assessing the relevance of the reversibility of age-related functional alterations for aging studies has been presented. Transduction mechanisms of adrenergic stimulation have been chosen as the target of age-related changes and thymus as the effector of some corrective interventions performed at advanced age. Both alterations of adrenoceptor characteristics and their reversibility have been reviewed. β-adrenoceptors have been studied in organs bearing only one subtype of receptors or both, revealing an age-related decrease in density only in the β1-subtype. It has been shown that a similar age-related decrease is present in α1-adrenoceptor density. Such alterations are corrected by grafting a neonatal thymus into old mice. On the contrary, thymus fails to correct the alteration of T4-induced upregulation of β-adrenoceptors indicating some limits to its corrective effect when the net of functional interrelationships becomes relatively complex. Both failures and successes of thymic grafts and thymic extracts in reversing age-related changes are discussed taking into account the effects induced on the life span of the animals. Different unsolved problems stemming from the previous considerations are also presented. Among them the controversial question about linearity and non-linearity of biological parameters presumed to be good indices of aging is discussed, with the aid of a simple model as a schematic example.