{"authors":[{"id":"dc5b778a-073c-449e-9e60-a93a1848f6cf","index":0,"name":"Wan Jin","role":"Author","type":"contributor"},{"id":"a366bc18-50f5-4621-a371-b1f048ef27cc","index":7,"name":"Jing Zheng","role":"Author","type":"contributor"},{"id":"3554bd0f-b5b2-4d55-898c-e7dcdf2fed2c","index":1,"name":"Yu Xiao","role":"Author","type":"contributor"},{"id":"7f8d5aab-ecd6-428f-b03f-44da2625c5ab","index":2,"name":"Lingao Ju","role":"Author","type":"contributor"},{"id":"32bb4d37-eddd-4c7a-9604-bad42e40c168","index":3,"name":"Fangjin Chen","role":"Author","type":"contributor"},{"id":"d145c899-1ee3-44e0-8b78-d6b00c03636f","index":4,"name":"Jie Fu","role":"Author","type":"contributor"},{"id":"df608eca-1435-4725-afc5-ef1d1c7af24b","index":5,"name":"Hui Jiang","role":"Author","type":"contributor"},{"id":"96335c9b-c3d7-4f64-9a8c-e2c921209b8c","index":6,"name":"Yi Zhang","orcid":"0000-0001-5388-1276","role":"Author","type":"contributor"}],"components":[{"id":"root","name":"root","payload":{"cid":"bafybeifhf5vhhkrq557hgmsvwnukqhnbfxj2ue4xmewxzp2krihhdkwcru","path":"root"},"type":{".pdf":"pdf",".jpg":"data"}},{"id":"5529b583-c67a-4c88-8e68-ba87124aa371","name":"2024.01.06.574476v1.full.pdf","payload":{"cid":"bafybeifb3sfgh5s7fwhnhzinxv4dl4empbytnei6lfalpi7q6mdnecmdo4","externalUrl":"https://www.biorxiv.org/content/10.1101/2024.01.06.574476v1.full.pdf","licenseType":"cc by","path":"root/preprint.pdf","title":"Preprint"},"starred":true,"subtype":"preprint","type":"pdf"},{"id":"7b3c9b1c-6f8b-4f02-8604-8e12b32c6be0","name":"G_quadruplex_aging_paper_2024","payload":{"cid":"bafybeif4forgie5klccfzwxs5ofouyyiv7yh7jstvrngth6dsxlch72oay","externalUrl":"https://github.com/MagpiePKU/G_quadruplex_aging_paper_2024","licenseType":"mit","path":"root/G_quadruplex_aging_paper_2024","title":"Code Scripts"},"starred":true,"subtype":"code-scripts","type":"code"},{"id":"edb1fca5-ad4c-4cd0-95aa-448349a0a26b","name":"supplementary-info.pdf","payload":{"cid":"bafybeidbq5p6ftl3usznrqeq3x2gwybhwaczqlntgwoo3v66ptjipqbgc4","licenseType":"cc by","path":"root/supplementary-info.pdf","title":"Supplementary Material"},"starred":true,"subtype":"supplementary-information","type":"pdf"}],"defaultLicense":"CC BY","description":"How cell replication ultimately results in aging and the Hayflick limit are not fully understood. Here we show that clock-like accumulation of DNA G-quadruplexes (G4s) throughout cell replication drives conserved aging mechanisms. G4 stimulates transcription-replication interactions to delay genome replication and impairs DNA re-methylation and histone modification recovery, leading to loss of heterochromatin. This creates a more permissive local environment for G4 formation in subsequent generations. As a result, G4s gradually accumulate on promoters throughout mitosis, driving clock-like DNA hypomethylation and chromatin opening. In patients and in vitro models, loss-of-function mutations in the G4-resolving enzymes WRN, BLM and ERCC8 accelerate the erosion of the epigenomic landscape around G4. G4-driven epigenomic aging is strongly correlated with biological age and is conserved in yeast, nematodes, insects, fish, rodents, and humans. Our results revealed a universal molecular mechanism of aging and provided mechanistic insight into how G-quadruplex processor mutations drive premature aging.","dpid":{"id":"217","prefix":"beta"},"researchFields":[],"title":"A universal molecular mechanism driving aging","version":"desci-nodes-0.2.0","coverImage":"bafybeiceysyp6d5yxq5l3qq5k344r5dovyvkfpx6et4t2fdoa6nguzi7ye"}