biostudies-literatureUnknownRamteke PNIA NIH HHSIntervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of <i>Sirt6</i> in the disc (<i>Acan</i> ^{<i>CreERT2</i>} ; <i>Sirt6</i> ^<i>fl/fl</i> ). Histological studies showed a degenerative phenotype in knockout mice compared to <i>Sirt6</i> ^<i>fl/fl</i> control mice at 12 months which became pronouncbioRxiv : the preprint server for biology2024.09.09.612072https://www.ebi.ac.uk/biostudies/studies/S-EPMC11419082biostudies-literatureSIRT6 loss causes intervertebral disc degeneration in mice by promoting senescence and SASP status.PMC11419082R01 AG078609R01 AG073349R01 AG044034Ramteke PCollins JABarve RAWatson BRisbud MVTsingas MJohnston STran VAMitra RToci MLoeser RFfalseSIRT6 loss causes intervertebral disc degeneration in mice by promoting senescence and SASP status.Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of <i>Sirt6</i> in the disc (<i>Acan</i> ^{<i>CreERT2</i>} ; <i>Sirt6</i> ^<i>fl/fl</i> ). Histological studies showed a degenerative phenotype in knockout mice compared to <i>Sirt6</i> ^<i>fl/fl</i> control mice at 12 months which became pronounc2024-01-01T00:00:00Z2024 Sep2026-04-21T03:21:26.402Z2025-04-06T14:24:32.954ZS-EPMC114190823931428210.1101/2024.09.09.612072