Article: Klotho mutation does not accelerate intervertebral disc aging in mice

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 (Kl/Kl) have a reduced lifespan and display accelerated aging phenotypes in several tissues, including the kidney, pancreas, bone, and brain. To test the suitability of Kl/Kl mice for studying accelerated disc pathologies, we characterized the lumbar discs of eight-week-old Kl/Kl mice compared to wild-type controls. No structural, morphological, or molecular differences were observed in the discs of Kl/Kl mice compared to controls. Next, we tested the hypothesis that Kl/Kl 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 Kl/Kl mutants.

Citing Articles

Klotho mutation does not accelerate intervertebral disc aging in mice.

Hong J, Shah V, Krishnan R, Gomez-Stallons M, Poudel S, Yutzey K FASEB J. 2025; 39(1):e70279.

PMID: 39760159 PMC: 11701877. DOI: 10.1096/fj.202402847R.

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Klotho Mutation Does Not Accelerate Intervertebral Disc Aging in Mice