{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324160/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Methylation profiling"],"species":["Mus musculus"],"gds_type":["Methylation profiling by array"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324160"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A progeria syndrome links DNA hypermethylation to age-related pathology [mouse]","description":"Declining tissue function and regenerative capacity underlie many chronic diseases. Experimentally establishing the mechanistic basis for such tissue ageing presents substantial challenges, given decades-long timescales and multifactorial origins. Epigenetic alterations have been proposed to have a key aetiological role, but whether they are correlative or causal remains a key unanswered question, as does their contribution to specific age-related pathologies. Here, we establish a novel epigenetically-driven accelerated ageing syndrome. We demonstrate that DNMT3A gain-of-function mutations in Heyn-Sproul-Jackson syndrome recapitulate age-related gains in DNA methylation, cause multilineage stem cell dysfunction, and phenocopy aspects of ageing in humans and mice. We also show that region-specific DNA hypermethylation at lineage-specific genes can explain reduced stem cell output and lineage skewing. Hence, starting from a Mendelian disorder, we causally implicate DNA methylation-mediated stem cell exhaustion in the aetiology of medically important age-related haematological, bone and metabolic pathologies, that might be targetable by future therapies.","dates":{"publication":"2026/04/27"},"accession":"GSE324160","cross_references":{"GSM":["GSM9570242","GSM9570243","GSM9570240","GSM9570241","GSM9570246","GSM9570247","GSM9570244","GSM9570245","GSM9570282","GSM9570283","GSM9570280","GSM9570281","GSM9570239","GSM9570237","GSM9570238","GSM9570253","GSM9570254","GSM9570251","GSM9570252","GSM9570213","GSM9570257","GSM9570214","GSM9570258","GSM9570255","GSM9570256","GSM9570212","GSM9570250","GSM9570248","GSM9570249","GSM9570220","GSM9570264","GSM9570265","GSM9570221","GSM9570262","GSM9570263","GSM9570224","GSM9570268","GSM9570225","GSM9570269","GSM9570222","GSM9570266","GSM9570267","GSM9570223","GSM9570260","GSM9570261","GSM9570217","GSM9570218","GSM9570259","GSM9570215","GSM9570216","GSM9570219","GSM9570231","GSM9570275","GSM9570276","GSM9570232","GSM9570273","GSM9570230","GSM9570274","GSM9570279","GSM9570235","GSM9570236","GSM9570233","GSM9570277","GSM9570234","GSM9570278","GSM9570271","GSM9570272","GSM9570270","GSM9570228","GSM9570229","GSM9570226","GSM9570227"],"GPL":["32685"],"GSE":["324160"],"taxon":["Mus musculus"]}}