The senescent methylome and its relationship with cancer, ageing and germline genetic variation in humans.

Published online

Journal Article

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.

Full Text

Cited Authors

  • Lowe, R; Overhoff, MG; Ramagopalan, SV; Garbe, JC; Koh, J; Stampfer, MR; Beach, DH; Rakyan, VK; Bishop, CL

Published Date

  • September 17, 2015

Published In

Volume / Issue

  • 16 /

Start / End Page

  • 194 -

PubMed ID

  • 26381124

Pubmed Central ID

  • 26381124

Electronic International Standard Serial Number (EISSN)

  • 1474-760X

Digital Object Identifier (DOI)

  • 10.1186/s13059-015-0748-4

Language

  • eng

Conference Location

  • England