环节性基因BMAL1 在甲状腺衰老中调节细胞衰老
Dandan Zong1, Baihui Sun2, Qiting Ye3
1Department of Endocrinology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Aging cell
|May 28, 2025
概括
衰老加速甲状腺细胞衰老,并损害激素功能. 昼夜节律基因BMAL1的干扰加剧了这种衰退,突出了甲状腺衰老的新机制.
科学领域:
- 老年学是指老年学的学科.
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 全球老龄化增加了甲状腺疾病的发病率,特别是老年人的甲状腺功能低下症.
- 甲状腺刺激激素 (TSH) 在老年人中升高,但甲状腺衰老及其对激素合成的影响尚不清楚.
- 细胞衰老及其在与年龄相关的甲状腺功能障碍中的作用需要进一步调查.
研究的目的:
- 为了研究老化的人类甲状腺中的分子和功能变化.
- 为了确定细胞衰老,昼夜节律和甲状腺激素合成之间的关系.
- 阐明BMAL1在甲状腺衰老和功能中的作用.
主要方法:
- 来自不同年龄组的人类甲状腺组织的单细胞RNA测序 (scRNA-seq).
- 分析与衰老相关的基因表达,包括甲状腺激素合成和衰老标志物.
- 使用甲状腺特异性Bmal1淘汰赛小鼠模型和细胞系实验进行验证.
主要成果:
- 甲状腺衰老开始较早,TH合成基因表达增加,以及表皮细胞中的衰老相关分泌表型 (SASP).
- 鉴定出一个功能减弱的衰老表皮细胞 (CDKN1A_EPI) 的子组.
- 昼夜基因BMAL1的下调加速衰老,并通过抑制NFkbia (NF-κB抑制剂α) 表达来损害甲状腺激素合成.
结论:
- 循环节律的破坏加速甲状腺细胞衰老,加剧甲状腺功能下降.
- BMAL1在维持甲状腺功能和预防衰老方面发挥着至关重要的作用.
- 这些发现为了解甲状腺衰老和维持甲状腺健康提供了新的理论基础.
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