Heterochromatin islands and their dynamic reorganization: A hypothesis for three distinctive features of cellular aging

The mechanism of cellular aging has been suggested to play an important role in organismic aging, but the molecular linkage between them is not still understood. The recent progress in the studies of telomere and telomerase demonstrates their substantial roles in the mechanism of cellular aging. On the other hand, these studies also raise controversial issues about the generality of the telomere hypothesis. The heterochronic, polymorphic, and probabilistic features of cellular aging should be reconsidered critically. In this review, we attempt to develop a general scheme for the driving force of cellular aging, based on our molecular and computational studies. Our molecular analyses suggest that global transcriptional repressive structures are essentially involved in cellular aging-associated transcriptional regulation. From our theoretical studies, systematic reorganization of these repressive structures are suggested to be a fundamental driving force of cellular aging. The heterochromatin island hypothesis is proposed to give a rational explanation for the three distinctive features of cellular aging. The importance of a dynamic equilibrium in heterochromatin islands is also discussed for cellular and organismic aging.