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两种保存的质甲基酶调节线粒体压力诱导的寿命
Carsten Merkwirth1, Virginija Jovaisaite2, Jenni Durieux3
1Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; The Glenn Center for Research on Aging, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; The Paul F. Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA 94720, USA.
轻微的线粒体应激通过激活未折叠蛋白质反应 (UPR) 有助于延长寿命. 表观遗传调节剂,基因组脱甲酶, 控制这种长寿途径, 从虫到小鼠,
科学领域:
- 细胞生物学
- 遗传学
- 老龄化研究
背景情况:
- 线粒体功能障碍与衰老和疾病有关.
- 展开的蛋白质反应 (UPR) 维持了线粒体的健康.
- 表观遗传机制与衰老和压力反应有关.
研究的目的:
- 调查线粒体应激对寿命的表观遗传调节.
- 确定参与长寿途径的特定基因.
- 探索线粒体平衡在衰老中的作用.
主要方法:
- 用C. elegans作为研究衰老和线粒体压力的模型生物.
- 使用基因操纵 (减少和增强功能) 的基因组甲基酶.
- 在BXD小鼠参考群体中应用系统遗传学,用于跨物种验证.
主要成果:
- 鉴定了保守的素脱甲基酶 (jmjd-1.2/PHF8和jmjd-3.1/JMJD3) 作为寿命的积极调节剂.
- 证明这些脱甲基酶的丧失抑制了长寿和UPR的诱导.
- 显示功能增长以UPR (mt) 取决的方式延长寿命.
- 已证实哺乳动物对长寿和UPR的保存作用.
结论:
- 一个进化保存的表观遗传机制调节了线粒体干扰的下游衰老.
- 线粒体压力对寿命的有益影响的关键介质是基因组脱甲酶.
- 针对这些表观遗传调节剂可能为与年龄相关的疾病提供治疗策略.
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