Clocked cell cycle clocks: implications toward chronopharmacology and aging.

Abstract

Cell developmental and division cycles, comprising relatively discrete morphological and biochemical events that may be ordered sequentially or in a branching network, constitute “clocks” themselves in a general sense. Yet abundant evidence exists in both unicellular protistan and algal populations and in cultured mammalian cells that the cell division cycle (and perhaps other related cyclic events) may itself be modulated (or “clocked”) by a circadian oscillatory mechanism (an endogenous, self-sustaining oscillation) that at one level is conceptually and operationally distinct from the cell division cycle itself, but nevertheless, must ultimately be associated with, and generated by, basic cell cycle processes since the oscillatory mechanism(s) is itself replicated during each cell division cycle. A summary of the empirical evidence for these assertions is given in the first section of this paper.