Age-related changes to lumbosacral spinal cord motoneurons that modulate bladder and bowel functions in male C 57 BL / 6 mice Conference Item

The Open University's repository of research publications and other research outputs Age-related changes to lumbosacral spinal cord motoneurons that modulate bladder and bowel functions in male C57BL/6 mice Conference Item (2013). Age-related changes to lumbosacral spinal cord motoneurons that modulate bladder and bowel functions in male C57BL/6 mice. Copyright and Moral Rights for the articles on this site are retained by the individual authors and/or other copyright owners. For more information on Open Research Online's data policy on reuse of materials please consult the policies page. Aging is the main risk factor for most chronic diseases, disabilities, and declining health. It has long been proposed that senescent cells—damaged cells that have lost the ability to divide –drive the deterioration that underlies aging and age-related diseases. However, definitive evidence for this relationship has been lacking. The use of a progeroid mouse model (which expresses low amounts of the mitotic checkpoint protein BubR1) has been instrumental in demonstrating that p16-positive senescent cells drive age-related pathologies and that selective elimination of these cells can prevent or delay age-related deterioration. Experiment designed to dissect how senescent cells develop in BubR1 progeroid mice and how they contribute to aging in this model will be presented. Senescent cells have become attractive therapeutic targets for the treatment of aging and age-related diseases. The potential applications and implications of such intervention strategies will be discussed. Replicative cellular senescence is an important tumor suppression mechanism and also contributes to aging. Progression of both cancer and aging include significant epigenetic components, but the chromatin changes that take place during cellular senescence are only beginning to emerge. We used high throughput methods to map the chromatin landscape in senescence. We report that senescent human cells exhibit widespread DNA hypomethylation and " chromatin opening " , but also more focal DNA hypermethylation and " chromatin closing ". Hypomethylation and chromatin opening occurs preferentially at gene-poor, late-replicating lamin-associated domains and is linked to mislocalization of the maintenance DNA methyltransferase (DNMT1) in cells approaching senescence. Low-level gains of methylation and chromatin closing are enriched in CpG islands and promoters. Paradoxically, global hypomethylation and hypermethylation of CpG islands and associated chromatin changes are also reported to be features of cancer cells. Hypermethylation of CpG islands promotes silencing of tumor suppressor genes. Global hypomethylation of cancer cells is thought to promote genome instability and de-repression of repeat elements, including retrotransposons. In turn, retrotransposition can also perturb …