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Ageing continued (Yeast are used in studies of ageing as their cells are…

- - - - Experiments on mice who had never had any Sir6 protein expressed when they were developing were small at birth and seemed normal, but from two weeks onwards had lots on conditions seen in ageing like loss of fat under the skin and spinal curvature. The mice died within one month- a normal mouse can live up to 2 years.
        
        Most HDACs deacetylate many different proteins- they are not very specific. Sir6 is different in that it is specific to deacetylating only lysine 9 and lysine 56 on the histone tails of H3. SIRT6 enzyme is in human cells to keep telomere structure healthy (it has been suggested).
        
        Acetylation at histone 3, amino acid 9 is associated with gene upregualtion and when SIRT6 removes the acetyl group, the amino acid can be methykated by other enzymes present in the cell methylation on histone 3 position 9 represses genes.
        
        Changing SIRT6 levels of expression changed expression of specific genes confirming that SIRT6 is needed for telomere healthy structure maintenance.
        
        SIRT6 is part of a -ve feedback cycle where high acetylation levels drives up the HDAC SIRT6- in mice with no SIRT6, when the gene is knocked out, levels of histone acetylation at these genes satys high because the -ve feedback loop is off. Expression of SIRT6 target genes is high.
        
        SIRT6's targets promote apoptosis or the cell going into senescence. This explains why mice with no SIRT6 had accelerated ageing. Cells had their senescence genes switched on too early.
        
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