Studies have shown a strong correlation between SIRT6 and aging, and Sirt6 is significantly associated with increased lifespan in mice,10,11 in centenarian humans9,40 as well as in long-lived species.41 Despite a prominent effect on skeletal tissues18,19 and aging, which is one of the major risk factors for disc degeneration, the role of SIRT6 in disc health has been largely undermined.42 Here, we show for the first time that conditional deletion of Sirt6 in the mouse intervertebral disc, significantly accelerates degeneration and promotes a severe senescent phenotype. This evidence concerns the gene SIRT6 and intervertebral disk degenerative disorder.