title: The senescent methylome and its relationship with cancer, ageing and germline genetic variation in humans.
abstract: BACKGROUND
  Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. Here, we perform methylome analysis of actively dividing and deeply senescent normal human epithelial cells.
  
  
  RESULTS
  We identify senescence-associated differentially methylated positions (senDMPs) from multiple experiments using cells from one donor. We find that human senDMP epigenetic signatures are positively and significantly correlated with both cancer and ageing-associated methylation dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, which are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that a single senDMP signature can be effectively reversed in a newly-developed protocol of transient senescence reversal.
  
  
  CONCLUSIONS
  The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that may lead to cancer and age-related diseases in humans.
authors.affiliation: The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Lowe
authors.affiliation: The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Marita G
authors.initials: MG
authors.lastname: Overhoff
authors.affiliation: The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Sreeram V
authors.initials: SV
authors.lastname: Ramagopalan
authors.affiliation: Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Garbe
authors.affiliation: Division of Surgical Sciences, Department of Surgery, Duke University Medical School, Durham, NC, 27710, USA.
authors.forename: James
authors.initials: J
authors.lastname: Koh
authors.affiliation: Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
authors.forename: Martha R
authors.initials: MR
authors.lastname: Stampfer
authors.affiliation: The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Beach
authors.affiliation: The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK. v.rakyan@qmul.ac.uk.
authors.forename: Vardhman K
authors.initials: VK
authors.lastname: Rakyan
authors.affiliation: The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK. c.l.bishop@qmul.ac.uk.
authors.forename: Cleo L
authors.initials: CL
authors.lastname: Bishop
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D014644:Genetic Variation; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16