Because every longevity-control gene eventually is eventually shown to interact with every other longevity-control gene, it is perhaps not surprising that SIRT1 deacetylates WRN, the protein whose gene is mutated in the devastating human progeria Werner’s Syndrome. Both the helicase and exonuclease activities of the WRN protein are more active in the deacetylated state; thus, the longevity-assurance gene (SIRT1) is responsible for boosting the activity of the major player in the cellular response to DNA damage (WRN), which is the way we’d expect it to work.

Two other recent reports describing progress on WRN reveal that the protein plays a significant role in DNA metabolism under normal growth and after DNA damage: WRN is required both for replication fork progression after genotoxic stress as well as suppressing the spontaneous formation of telomeric DNA circles. These latter structures (which remind me of the extrachromosomal ribosomal DNA circles from the early years of the sirtuin field) are associated with both telomere shortening and cellular senescence.