The study identifies SIRT6 as a histone H3 lysine 9 (H3K9) deacetylase that modulates telomeric chromatin. SIRT6 is specifically associated with telomeres and its depletion leads to telomere dysfunction, premature cellular senescence, and chromosomal fusions. SIRT6-depleted cells exhibit abnormal telomere structures similar to those observed in Werner syndrome, a premature ageing disorder. SIRT6 deacetylates H3K9 at telomeres, which is essential for the stable association of WRN, a factor mutated in Werner syndrome. The findings link chromatin regulation by SIRT6 to telomere maintenance and premature ageing.The study identifies SIRT6 as a histone H3 lysine 9 (H3K9) deacetylase that modulates telomeric chromatin. SIRT6 is specifically associated with telomeres and its depletion leads to telomere dysfunction, premature cellular senescence, and chromosomal fusions. SIRT6-depleted cells exhibit abnormal telomere structures similar to those observed in Werner syndrome, a premature ageing disorder. SIRT6 deacetylates H3K9 at telomeres, which is essential for the stable association of WRN, a factor mutated in Werner syndrome. The findings link chromatin regulation by SIRT6 to telomere maintenance and premature ageing.