One of the causes of ageing is thought to be the accumulation of senescent cells. Since normal ageing is very complex, diseases with single gene mutations (progeroid syndromes) which show many features of normal ageing have been used as models in ageing research. Werner's syndrome is the progeroid syndrome which mimics most of the features of normal ageing. It is caused by a mutation of the WRN gene that encodes a RecQ helicase/exonuclease involved in DNA fork stabilization and repair during synthesis. Werner's syndrome fibroblasts have been shown to exit their replicative lifespan three to five times more rapidly than normal fibroblasts. The mechanisms of Werner's syndrome senescence have been extensively studied in fibroblasts. However, it is clear that accelerated replicative senescence is not a universal feature of the disease in all tissues. Thus, it is important to study the relationship between Werner's syndrome senescence in different tissue lineages. Donor to donor differences in replicative potential are also known to occur, thus it would be advantageous if replicative lifespan could be studied in cells with isogenic backgrounds.
|Date of Award||Sep 2012|