ArticleGenes & development2020
Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence.
Article in Genes & development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 papers, 1 of them a synthesis that pooled it.
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Who cites it
229 citing papers in PubMed, 1 synthesis or guideline pooled it, 320 citations in OpenAlex.
- Broad repression of DNA repair genes in senescent cells identified by integration of transcriptomic data.Nucleic acids research · 2025Pooled it
- Mechanistic reprogramming of the mtDNA-cGAS-STING axis in cellular senescence: from mitochondrial homeostatic disruption to inflammatory and immune outcomes.Biogerontology · 2026Review
- Clinical translation of senescence-related pan-cancer multi-omics: tools for assessment and immunotherapy prediction.Cancer gene therapy · 2026Article
- A pH-Responsive fluorescence lifetime probe reveals GOT1 phase separation in cellular anti-senescence.Smart molecules : open access · 2026Article
- Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline.Nature aging · 2026Article
- The organellar biology of aging: A mitochondrial vantage.Molecular biology reports · 2026Review
- The cGAS-STING pathway in inflammaging and neuroinflammation.Science China. Life sciences · 2026Review
- The Role of Skeletal Muscle Mitochondria in NLRP3 Inflammasome Signaling.Biomolecules · 2026Review
- NAMPT activation uncovers a senescence-specific vulnerability and promotes healthy aging in combination with NAM.bioRxiv : the preprint server for biology · 2026Article
- SenFlag gene signature identifies senescent cells in mouse and human tissues through a conserved core transcriptional program.The EMBO journal · 2026Article
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- Crosstalk collapse: mitochondria-centric organelle network disruption in ovarian aging.Cell communication and signaling : CCS · 2026Review
- Huashi Baidu formula may attenuate adriamycin-induced myocardial injury via modulating NRF2-ATF3-SRXN1 axis-mediated ferroptosis.Chinese herbal medicines · 2026Article
- Review
- Endothelial extracellular vesicles preserve vascular smooth muscle cell identity but do not reverse endothelial senescence.npj aging · 2026Article
- Molecular mechanisms and recent advances in cellular senescence.Cell & bioscience · 2026Review
- From energy metabolic homeostasis to immune remodeling: the role and therapeutic potential of STING signaling in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Review
- Nuclear export of R-loop by the DDX1 and XPO1 complex promotes senescence-associated secretory phenotype and inflammaging.Nature aging · 2026Article
- Mitochondrial DNA as a driver of inflammation via the cGAS-STING pathway.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
169 more citing papers are in PubMed but not listed here.
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19 authors at 8 institutions in 2 countries.
Funding
Abstract
Cellular senescence is a potent tumor suppressor mechanism but also contributes to aging and aging-related diseases. Senescence is characterized by a stable cell cycle arrest and a complex proinflammatory secretome, termed the senescence-associated secretory phenotype (SASP). We recently discovered that cytoplasmic chromatin fragments (CCFs), extruded from the nucleus of senescent cells, trigger the SASP through activation of the innate immunity cytosolic DNA sensing cGAS-STING pathway. However, the upstream signaling events that instigate CCF formation remain unknown. Here, we show that dysfunctional mitochondria, linked to down-regulation of nuclear-encoded mitochondrial oxidative phosphorylation genes, trigger a ROS-JNK retrograde signaling pathway that drives CCF formation and hence the SASP. JNK links to 53BP1, a nuclear protein that negatively regulates DNA double-strand break (DSB) end resection and CCF formation. Importantly, we show that low-dose HDAC inhibitors restore expression of most nuclear-encoded mitochondrial oxidative phosphorylation genes, improve mitochondrial function, and suppress CCFs and the SASP in senescent cells. In mouse models, HDAC inhibitors also suppress oxidative stress, CCF, inflammation, and tissue damage caused by senescence-inducing irradiation and/or acetaminophen-induced mitochondria dysfunction. Overall, our findings outline an extended mitochondria-to-nucleus retrograde signaling pathway that initiates formation of CCF during senescence and is a potential target for drug-based interventions to inhibit the proaging SASP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.