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 wh...

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Bibliographic Details
Published in:Science advances 2021-12, Vol.7 (51), p.eabj9111-eabj9111
Main Authors: Lee, Jun-Yeong, Davis, Ian, Youth, Elliot H H, Kim, Jonghwan, Churchill, Gary, Godwin, James, Korstanje, Ron, Beck, Samuel
Format: Article
Language:English
Subjects:
Biomedicine and Life Sciences
Diseases and Disorders
SciAdv r-articles
Systems Biology
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Summary: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.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abj9111