Telomeric epigenetic response mediated by Gadd45a regulates stem cell aging and lifespan.

ABSTRACT: Progressive attrition of telomeres triggers DNA damage response (DDR) and limits the regenerative capacity of adult stem cells during mammalian aging. Intriguingly, telomere integrity is not only determined by telomere length but also by the epigenetic status of telomeric/sub-telomeric regions. However, the functional interplay between DDR induced by telomere shortening and epigenetic modifications in aging remains unclear. Here, we show that deletion of Gadd45a improves the maintenance and function of intestinal stem cells (ISCs) and prolongs lifespan of telomerase-deficient mice (G3Terc^-/-). Mechanistically, Gadd45a facilitates the generation of a permissive chromatin state for DDR signaling by inducing base excision repair-dependent demethylation of CpG islands specifi

SUBMITTER: Diao D 

PROVIDER: S-EPMC6172461 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature