Introduction

A common theme in this volume is the association of chromosomal instability with aging. The notion of chromosomal instability, of course, can be considered at multiple levels, with breaks, heteroploidy, and other cytogenetic abnormalities being only its most readily visualized aspects. Cumulative defects are known to accumulate at the submicroscopic level, including, for example, point mutations, small deletions, and shortening of telomeres. Each of these types of age-related instabilities produces heritable alterations in DNA sequence and associated gene function. Evolutionarily conserved mechanisms exist, however, to generate heritable changes in the cell state without altering the primary DNA sequenceā€”such mechanisms provide the basis for epigenetic inheritance. The term epigenetic encompasses both covalent modifications to DNA (e.g., methy-lation of cytosine residues in mammals) and self-templating higher order chro-matin structures. The latter have been studied intensively in a number of systems (Table 1), but only recently have received more than passing attention within the aging field. This chapter will provide a brief overview of the current understanding of chromatin-based structures, emphasizing how instability in such chromosomal elements might contribute to senescence at cellular and organismal levels.

Table 1 Selected Examples of Epigenetically Inherited Silencing3

In mammals

In yeast

X chromosome inactivation

Mating-type silencing

Imprinting

Silencing at telomeres, rDNA repeats

In Drosophila

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