ageing mechanisms

A protein that regulates lifespan in yeast by its genome may function in the same manner in mammals, or more specifically the mouse. The protein is a family of proteins called sirtuins. .
In yeast sirtuin , called Sir2 is a guard and protector of the organism’s genome, preventing genes from expressed at the wrong time and blocking the chromosomal rearrangements that sometimes occur in areas of repetitive DNA sequence. When DNA strands break, Sir2 molecules move to repair the damage, leaving their usual positions unguarded. As cells age, the rate of DNA damage increases, forcing Sir2 proteins to leave their original posts more frequently. Some genes that were meant to be silenced are then free to be expressed, generat¬ing a shift in patterns of gene expression that is characteristic of ageing.
Increasing Sir2 levels slows ageing in yeast, but it is unclear whether sirtuins would act by a similar mechanism in mammals. David Sinclair and his colleagues have shown that a mouse sirtuin SIRT1 behaves much like its yeast counterpart (P. Oberdoerffer et al. Cell doi: 10.1016/j. cell.2008.10.025; 2008). In mouse embryonic stem cells, SIRTI also associates with regions of repetitive DNA, and silences the expression of certain genes. But when the cells are treated with hydrogen peroxide, a chemical that can cause DNA damage, SIRTI is recruited to the site of DNA breakage, and previously silenced genes become expressed. Similar changes in gene-expression patterns in brains of elderly mice were found
Ledford 2008 Mice share yeast’s ageing system. Nature Vol 456 p 433

Martin Eastwood
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