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Mitochondrial metabolism and epigenetic crosstalk drive the SASP (ChIP-seq)

GSE279410 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 30 samples Submitted 2026/05/19 Platform GPL34295
Summary
Senescent cells drive age-related tissue dysfunction largely through the persistent activation of the senescence-associated secretory phenotype (SASP). Here, we identify key mitochondrial metabolic pathways, including the mitochondrial citrate carrier (SLC25A1) and ATP-citrate lyase (ACLY), as critical regulators of the SASP. These pathways fuel histone acetylation at SASP gene loci, promoting their expression. Targeted inhibition of SLC25A1 or ACLY suppresses SASP expression without affecting cell cycle arrest, underscoring their potential as selective therapeutic targets for mitigating age-related inflammation. Furthermore, pharmacological inhibition of SLC25A1 reduces systemic inflammation and extends healthspan in aged mice. Our findings suggest that disrupting metabolic reprogramming in senescent cells offers a promising strategy to ameliorate aging-associated pathologies.
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Direct links to NCBI, no account and no request form: the whole study as GSE279410_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 30 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1172660 and SRA study SRP538448. Searching any of these in the dataset finder brings you back here.

Study design
10 conditions, mostly in triplicate
H3 Parkin Prolif ×3 H3 Parkin Sen(IR) ×3 H3 Parkin Sen(IR) + CCCP ×3 H3K27ac Parkin Prolif ×3 H3K27ac Parkin Sen(IR) ×3 H3K27ac Parkin Sen(IR) + CCCP ×3 H3 MRC5 Sen(IR) DMSO ×3 H3 MRC5 Sen(IR) CTPI2 ×3 +2 more

Supports a between-group comparison across 30 samples.

10 replicated groups read from 30 sample titles; they account for 30 of them. Check it against the sample list below before relying on it.

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