Imai and Kitano 1998 heterochromatin islands hypothesis for cellular aging
https://pubmed.ncbi.nlm.nih.gov/9789733/
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.
The heterochromatin loss model of aging
https://pubmed.ncbi.nlm.nih.gov/9315443/
There are significant changes in gene expression that occur with cellular senescence and organismic aging. Genes residing in compacted heterochromatin domains are typically silenced due to an altered accessibility to transcription factors. Heterochromatin domains and gene silencing are set up in early development and were initially believed to be maintained for the remainder of the lifespan. Recent data suggest that there may be a net loss of heterochromatin with advancing age in both yeast and mice. The gradual loss of heterochromatin-induced gene silencing could explain the changes in gene expression that are closely linked with aging. A general model is proposed for heterochromatin loss as a major factor in generating alterations in gene expression with age. The heterochromatin loss model is supported by several lines of evidence and suggests that a fundamental genetic mechanism underlies most of the changes in gene expression observed with senescence.
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