在老化的软骨中识别的衰老内型体现在血液代谢组中
Ilja Boone1, Margo Tuerlings1, Rodrigo Coutinho de Almeida1
1Section of Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, PO Box 9600, Post-zone S-05-P, 2300 RC, Leiden, The Netherlands.
GeroScience
|November 14, 2023
概括
骨关节炎软骨中的细胞衰老异质性揭示了不同的内型. 血液代谢概况反映了这些细胞状态,为向性关节炎治疗提供了潜在的非侵入性生物标志物.
科学领域:
- 生物医学科学 生物医学科学
- 细胞生物学 细胞生物学
- 骨关节炎研究 骨关节炎研究
背景情况:
- 陈年细胞的积累表达老化相关的分泌表现型 (SASP) 破坏组织平衡,导致诸如骨关节炎 (OA) 这样的疾病.
- 了解老化组织中细胞衰老的异质性对于开发有效的治疗策略至关重要.
研究的目的:
- 在老化的关节软骨中描述细胞衰老的异质性.
- 探索血液中相应的代谢特征,可以作为OA的生物标志物.
- 确定OA中不同老化内型的潜在治疗点.
主要方法:
- 对来自老年关节软骨RNA测序数据 (N=57) 的131个衰老基因基因组进行了集群分析.
- 无监督的等级聚类和途径分析确定了细胞衰老的内型.
- 从重叠的血液样本 (N=21) 中生成和分析了代谢概况.
主要成果:
- 在老化的关节软骨中发现了两种不同的细胞衰老内型.
- 末型-1的特征是细胞增殖途径 (例如FOXO4,RBL2,CDKN1B),FOXO介导的细胞周期是潜在的目标.
- 末型-2 呈现了丰富的炎症相关通路 (例如IL6,MMP1/3,VEGFC) 和SASP通路,这表明它们是治疗点.
- 在基于血的血液样本中观察到两个相应的代谢,与细胞内型相关.
结论:
- 在OA软骨中,细胞衰老是异质的,呈现出不同的内型,具有不同的路径丰富.
- 血代谢资料可以作为反映这些细胞衰老状态的非侵入性生物标志物.
- 这些发现支持开发针对患者量身定制的疗法,以针对骨关节炎的特定衰老途径.
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