A team at Thomas Jefferson University uses a mouse model lacking SIRT6 in spinal disc cells to show that SIRT6 deficiency elevates histone acetylation, DNA damage, and cellular senescence, while impairing autophagy, thereby accelerating intervertebral disc degeneration.

Key points

• Conditional deletion of Sirt6 in AcanCreERT2;Sirt6fl/fl mice accelerates lumbar and caudal disc degeneration.
• Loss of SIRT6 elevates H3K9 acetylation, disrupts chromatin accessibility, and alters transcriptomic SASP signatures.
• Sirt6 deficiency increases γH2AX DNA-damage foci, raises p21/p19 levels, and decreases LC3-mediated autophagy in disc cells.

Why it matters: Identifying SIRT6 as an epigenetic gatekeeper of disc health suggests new therapeutic strategies to combat age-related spinal degeneration.