Senescence and the Genome
Bridger, Joanna M
Cellular senescence is commonly initiated in response to replicative or cell stress pathways. Senescent cells remain in a state of permanent cell cycle arrest and although being metabolically active, they exhibit distinct senescence phenotypes. Though cellular senescence may be beneficial in tumour suppression and wound healing, it is commonly associated with age-related diseases. There are various mechanisms and drivers that contribute to ageing, but it is becoming increasing apparent that processes related to chromatin and the epigenome are also important. Indeed, three of the nine hallmarks of ageing are genome specific including: genomic instability, epigenetic alterations and telomere attrition. With the advent of new technologies like DNA adenine methyltransferase identification and chromosome conformation capture, the features and complexity of the ageing genome are being revealed. This chapter will address key characteristics of interphase nuclei during cellular senescence including the spatio-temporal organisation of chromosomes, chromatin remodelling and epigenome changes.