A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A

Sirtuin 6 (SIRT6) is a deacylase and mono-ADP-ribosyltransferase enzyme implicated in multiple aging-related pathways including DNA repair, telomere maintenance, and metabolism regulation. A strong correlation between SIRT6 activity and longevity has been observed across species, and genetic polymorphisms in the SIRT6 gene correlate with human longevity in SNP analyses. To demonstrate that the centSIRT6 allele improves DNA repair efficiency, the authors used the CellRaft AIR system to isolate monoclonal mesenchymal stem cells (MSCs) with a centSIRT6 knock-in. MSCs with the centSIRT6 allele demonstrated a higher efficiency of DNA repair and increased survival upon treatment with methyl methanesul-fonate, a potent DNA-damaging agent, supporting the hypothesis that the centSIRT6 allele contributes to human longevity by improving genome maintenance.