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细胞外HMGB1的衰老表型的传播取决于它的氧化还原状态

Ji-Won Shin¹, Dong-Hyun Jang¹, So Young Kim²

¹Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Republic of Korea.

Metabolism: clinical and experimental

|April 6, 2025

概括

红氧敏感高流动性组盒1 (ReHMGB1) 驱动全身细胞衰老. 准细胞外HMGB1可能会预防与衰老相关的疾病.

科学领域:

细胞和分子生物学细胞和分子生物学
衰老研究研究衰老研究
免疫学免疫学免疫学

背景情况:

细胞衰老通过循环系统传播,但机制尚不清楚.
高流动性组盒1 (HMGB1) 是一种与衰老相关的分泌表型 (SASP) 因子,具有各种氧化还原状态.
研究了红氧敏感HMGB1 (ReHMGB1) 在全身衰老中的作用.

研究的目的:

调查ReHMGB1在驱动膜和全身衰老中的作用.
为了评估不同的HMGB1氧化还原状态对细胞衰老的 in vitro 和 in vivo 影响.
在肌肉损伤模型中评估HMGB1阻断的治疗潜力.

主要方法:

用于评估ReHMGB1效应的对膜衰老模型.
在体外和体内的实验与细胞外HMGB1氧化还原状态.
衰老标志物 (SA-β-gal,EdU,p16INK4a,p21) 通过染色,RT-qPCR和西斑进行评估.
大量RNA测序和细胞因子阵列用于途径和SASP分析.
在年轻小鼠和中年老鼠肌肉损伤模型中的体内研究.

主要成果:

细胞外ReHMGB1诱导了多种细胞类型和组织中的衰老类型的表型.
转录组分析显示RAGE介导的JAK/STAT和NF-κB通路的激活.
在体内,ReHMGB1的使用增加了衰老标志物;HMGB1的抑制减少了衰老,炎症和增强了肌肉再生.

结论:

ReHMGB1作为一个依赖于氧化还原的亲老年性因子,驱动全身衰老.
准细胞外HMGB1显示了与衰老相关的疾病的治疗潜力.

关键词:

细胞衰老细胞衰老细胞外HMGB1 细胞外HMGB1 副膜衰老是一种衰老现象.氧化还原剂的使用方法在 SASP 找 SASP

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