Aging is a risk factor for several chronic conditions, including intervertebral disc degeneration and associated back pain. Disc pathologies include loss of reticular-shaped nucleus pulposus cells, disorganization of annulus fibrosus lamellae, reduced disc height, and increased disc bulging. Sonic hedgehog, cytokeratin 19, and extracellular matrix proteins are markers of healthy disc. Preclinical murine models help understand cellular and molecular mechanisms of disc pathologies and the associated neurological symptoms. Klotho (Kl) is a known anti-aging gene. Kl-deficient mice (KlKl/KlKl) have a reduced lifespan and display accelerated aging phenotypes in several tissues, including the kidney, pancreas, bone, and brain. To test the suitability of KlKl/KlKl mice for studying accelerated disc pathologies, we characterized the lumbar discs of eight-week-old KlKl/KlKl mice compared to wild-type controls. No structural, morphological, or molecular differences were observed in the discs of KlKl/KlKl mice compared to controls. Next, we tested the hypothesis that KlKl/KlKl mice do not display accelerated disc pathologies due to the absence of Kl expression or response by disc cells. Multiplex qPCR analysis did not detect any Kl isoforms in the disc cells, explaining the absence of disc phenotype in KlKl/KlKl mutants.
Keywords: accelerated aging; annulus fibrosus; degeneration; intervertebral disc; klotho; nucleus pulposus; sonic hedgehog.
© 2025 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.