biostudies-literatureWang MShenzhen Medical Research FundCAS Youth Interdisciplinary Team, Space Medical Experiment Project of CMSPProgram of the Beijing Natural Science FoundationNational Natural Science Foundation of ChinaExcellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher TeamNew Cornerstone Science Foundation through the XPLORER PRIZEInitiative Scientific Research Program, Institute of Zoology, CASBeijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research InstitutesStrategic Priority Research Program of the Chinese Academy of SciencesYouth Innovation Promotion Association of CASInformatization Plan of Chinese Academy of SciencesYoung Elite Scientists Sponsorship Program by CASTCAS Project for Young Scientists in Basic ResearchNational Key Research and Development Program of ChinaKey Laboratory of Alzheimer's Disease of Zhejiang ProvinceExcellent Young Talents Program of Capital Medical UniversityKey Laboratory of Alzheimer’s Disease of Zhejiang Province667-684https://www.ebi.ac.uk/biostudies/studies/S-EPMC12342153biostudies-literatureUnknown16(8)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 Protein & cellSingle-nucleus transcriptomics decodes the link between aging and lumbar disc herniation.PMC12342153JYY2023-1382322025ZJAD-2024001823611481312022YFA1103700YSBR-0122022YFA1103800STI2030-Major Projects-2021ZD0202400YSBR-076XDA0460403823611481302021-10458247158682271600Z2300112020YFA080400082311016262022083HYZHXMH01012C2406001JQ24044824220318248830112300927XDC020000082125011CAS-WX2022SDC-XK14321210013234100192468303921682012023IOZ01022023IOZ02022024IOZ010382192863Z2400182021QNRC001BPHR20220310582330044Li JMa SWang ALi CLei JLiu GHQu JYang CWang MZhang WHe ZWang SSun SYu ZLiu FYu YfalseSingle-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 2025-01-01T00:00:00Z2025 Aug2026-05-01T18:41:42.181Z2026-04-18T03:08:12.818ZS-EPMC123421534011968110.1093/procel/pwaf025