Misexpression of genes lacking CpG islands drives degenerative changes during aging.

Cellular aging is characterized by disruption of the nuclear lamina and its associated heterochromatin. How these structural changes within the nucleus contribute to age-related degeneration of the organism is unclear. Genes lacking CpG islands (CGI − genes) generally associate with heterochromatin when they are inactive. Here, we show that the expression of these genes is globally activated in aged cells and tissues. This CGI − gene misexpression is a common feature of normal and pathological aging in mice and humans. We report evidence that CGI − gene up-regulation is directly responsible for age-related physiological deterioration, notably for increased secretion of inflammatory mediators.