Single-nucleus transcriptomics decodes the link between aging and lumbar disc herniation
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.
Authors
- Fei‐Fei Liu (ORCID: https://orcid.org/0000-0003-4344-6486)
- Jinghui Lei
- Zan He (ORCID: https://orcid.org/0000-0002-9241-8652)
- Shuai Ma (ORCID: https://orcid.org/0000-0002-8858-4383)
- Cunyu Yan (ORCID: https://orcid.org/0000-0002-3603-2421)
- Jing Qu (ORCID: https://orcid.org/0000-0002-3988-5067)
- Jiaming Li (ORCID: https://orcid.org/0000-0003-2141-7561)
- Min Wang (ORCID: https://orcid.org/0000-0002-6495-5637)
- Anqi Wang (ORCID: https://orcid.org/0000-0003-0344-5219)
- Guang‐Hui Liu (ORCID: https://orcid.org/0000-0001-9289-8177)
- Shuhui Sun (ORCID: https://orcid.org/0000-0003-1051-4067)
- Chunde Li (ORCID: https://orcid.org/0000-0001-9164-5725)
- Weiqi Zhang
- Zhengrong Yu (ORCID: https://orcid.org/0009-0005-6979-9935)
- Chengxian Yang
- Si Wang (ORCID: https://orcid.org/0009-0009-3691-4158)
Institutions
- University of Science and Technology of China (CN)
- Sun Yat-sen University (CN)
- Capital Medical University (CN)
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Beijing Institute of Genomics (CN)
- Biomarker Technologies (China) (CN)
- Beijing Geriatric Hospital (CN)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Beijing Anding Hospital (CN)
- Beijing Anzhen Hospital (CN)
- Peking University First Hospital (CN)
- Sun Yat-sen University Cancer Center (CN)
- Shanghai Center For Bioinformation Technology (CN)
- University of Chinese Academy of Sciences (CN)
- Institute of Zoology (CN)
Publication Details
- Journal
- Protein & Cell
- Published
- 2025-03-22
- DOI
- https://doi.org/10.1093/procel/pwaf025
- Citations
- 7
- Primary Topic
- Spine and Intervertebral Disc Pathology
- Type
- article
- Field-Weighted Citation Impact
- 10.30