THE HETEROCHROMATIN LOSS MODEL OF AGING

There are significant changes in gene expression that occur with cellu lar senescence and organismic aging. Genes residing in compacted heter ochromatin domains are typically silenced due to an altered accessibil ity to transcription factors. Heterochromatin domains and gene silenci ng are set up in early development and were initially believed to be m aintained 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 silen cing could explain the changes in gene expression that are closely lin ked with aging. A general model is proposed for heterochromatin loss a s a major factor in generating alterations in gene expression with age . The heterochromatin loss model is supported by several lines of evid ence and suggests that a fundamental genetic mechanism underlies most of the changes in gene expression observed with senescence. (C) 1997 E lsevier Science Inc.