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Papers of the Week


Papers: 4 Jan 2025 - 10 Jan 2025


2025 Jan 15


FASEB J


39760159


39


1

Klotho mutation does not accelerate intervertebral disc aging in mice.

Authors

Hong J, Shah V, Krishnan R, Gomez-Stallons MV, Poudel S, Yutzey KE, Dahia CL

Abstract

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.