氨酸特异性脱甲基酶1 (LSD1) 通过依赖于 рибофлавин吸收的脱甲基化活动抑制细胞衰老
Taiichi Osumi1, Taiki Nagano2, Tetsushi Iwasaki1,2
1Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, 657-8501, Japan.
Scientific reports
|February 23, 2025
概括
细胞衰老被增加的黄氨酸二核酸 (FAD) 水平抑制,这增强了氨酸特异性脱甲酶1 (LSD1) 活性. 这种依赖FAD的LSD1脱甲基化抑制了亲衰老基因,防止永久性细胞循环停止.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞衰老是一种不可逆转的细胞循环停止状态,由各种压力因素引发.
- riboflavin 载体 SLC52A1 的表达在衰老过程中增加,而它的产物 - - 黄氨酸二核酸 (FAD) 抑制衰老.
- 通过FAD抑制细胞衰老的确切机制尚不清楚.
研究的目的:
- 研究氨酸特异性脱甲酶1 (LSD1) 在FAD介导的细胞衰老抑制中的作用.
- 阐明FAD如何影响LSD1活动及其下游目标在衰老的背景下.
主要方法:
- 研究了LSD1抑制和过度表达对DNA损伤引起的衰老的影响.
- 在诱导衰老的条件下,评估了LSD1对素H3和p53的去甲基化活性.
- 分析了亲衰老基因 (Sirtuin-4,p21) 与LSD1活动和FAD水平相关的表达.
主要成果:
- 抑制LSD1促进了衰老,而LSD1过度表达则抑制了衰老.
- 诱导衰老的压力增加了RSD1脱甲基化活性,以依赖于利博弗拉吸收的方式.
- 激素H3和p53的LSD1去甲基化对于抑制促衰老基因Sirtuin-4和p21至关重要.
结论:
- 在衰老期间增加的FAD水平增强了LSD1的活动.
- 在FAD-依赖的LSD1脱甲基化素H3和p53抑制关键的亲衰老基因.
- 这一途径代表了一种抑制细胞衰老诱导的新机制.
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