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

ABSTRACT: 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.

SUBMITTER: Lee JY 

PROVIDER: S-EPMC8673774 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature