The molecular events that lead to human aging are poorly understood. Werner syndrome, which is characterized by premature aging, is caused by recessive mutations in the WRN gene. Juan Carlos Izpisua Belmonte, Guang-Hui Liu, Fuchou Tang and colleagues derived human embryonic stem cells that lack WRN protein to model Werner syndrome in vitro and to illuminate the mechanisms that underlie precocious aging (Science doi:10.1126/science.aaa1356; 30 April 2015). The authors differentiated WRN-null embryonic stem cells to mesenchymal stem cells and observed several signs of premature cellular aging, a global reduction in H3K9me3 histone methylation and alterations in heterochromatin patterns. They demonstrated that WRN associates with the heterochromatin proteins SUV39H1 and HP1α as well as with LAP2β, a nuclear lamina–heterochromatin anchoring protein. Indeed, knocking in a catalytically inactive form of SUV39H1 in wild-type mesenchymal stem cells accelerated cellular senescence and resulted in a phenotype mimicking that of WRN-null mesenchymal stem cells. Interestingly, mesenchymal stem cells from older individuals showed a reduction in WRN expression and heterochromatin marks. Taken together, these findings show that WRN helps maintain heterochromatin stability and suggest a role for heterochromatin disorganization in human aging. It will be interesting to study the function of WRN in diverse cell lineages, particularly in vivo.