Single-nucleus Transcriptomics Decodes the Link Between Aging and Lumbar Disc Herniation.

Min Wang, Zan He, Anqi Wang, Shuhui Sun, Jiaming Li, Feifei Liu, Chunde Li, Chengxian Yang, Jinghui Lei, Yan Yu, Shuai Ma, Si Wang, Weiqi Zhang, Zhengrong Yu, Guang-Hui Liu, Jing Qu

Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. · pubmed

Paper

Abstract

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.

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Research summary

The study identifies cellular senescence and molecular alterations in the nucleus pulposus as key mechanisms linking aging and lumbar disc herniation. This research is relevant as it explores the underlying biological processes of aging, potentially guiding therapeutic strategies that address root causes rather than just symptoms.

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