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Centromere inactivation during aging can be rescued in human cells

GSE250322 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2025/01/13 Platform GPL18573
Summary
Aging involves a range of genetic, epigenetic, and physiological alterations. A key characteristic of aged cells is the loss of global heterochromatin, accompanied by a reduction in canonical histone levels. In this study, we track the fate of centromeres during aging in human cells. Our findings reveal that the centromeric histone H3 variant CENP-A is downregulated in aged cells, in a p53-dependent manner. We observe repression of centromeric noncoding transcription through an epigenetic mechanism via recruitment of a lysine-specific demethylase 1 (LSD1/KDM1A) at the centromeric DNA. This suppression results in defective de novo CENP-A loading at aging centromeres. By dual inhibition of p53 and the lysine-specific demethylase 1 in aged cells, we mitigate the reduction in centromeric proteins and centromeric transcripts, leading to the rejuvenation of these cells. These results offer insights into a novel mechanism for centromeric inactivation during aging and provide valuable information on strategies to reactivate it.
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Also filed as BioProject PRJNA1053365 and SRA study SRP478303. Searching any of these in the dataset finder brings you back here.

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