Abstract: | Dear Editor,Ten-eleven translocation(Tet)enzymes play important roles in DNA demethylation involved in various biological pro-cesses including stem cell pluripotency and differentiation,and tumorigenesis(Dawlaty et al.,2013;Wu and Zhang,2017).Tet2 deficiency or mutation leads to severe hematopoietic defects or myeloid malignancies in mice(Delhommeau et al.,2009;Ko et al.,2010;Moran-Crusio et al.,2011).Restoration of TET2 blocks aberrant self-re-newal and leukemia progression in patients possessing TET2 mutations(Cimmino et al.,2017).DNA methylation-based biomarkers,or"epigenetic clocks",link developmental and maintenance processes to biological aging(Horvath and Raj,2018).Interestingly,age-associated TET2 mutations have been found to drive myeloid dysfunction,cancer and cardiovascular disease(review(Ferrone et al.,2020)).Nevertheless,there has been lack of direct evidence demonstrating that Tet2 mutations or deficiency can actually accelerate aging. |