粒体自噬
自噬
氧化应激
生物
线粒体
细胞生物学
氧化磷酸化
人口
生物化学
细胞凋亡
医学
环境卫生
作者
Vijigisha Srivastava,Veronica Zelmanovich,Virendra Shukla,Rachel Abergel,Irit Cohen,Shmuel A. Ben-Sasson,Einav Gross
出处
期刊:Autophagy
[Informa]
日期:2022-05-17
卷期号:19 (2): 474-504
被引量:3
标识
DOI:10.1080/15548627.2022.2078069
摘要
Impaired mitophagy is a primary pathogenic event underlying diverse aging-associated diseases such as Alzheimer and Parkinson diseases and sarcopenia. Therefore, augmentation of mitophagy, the process by which defective mitochondria are removed, then replaced by new ones, is an emerging strategy for preventing the evolvement of multiple morbidities in the elderly population. Based on the scaffold of spermidine (Spd), a known mitophagy-promoting agent, we designed and tested a family of structurally related compounds. A prototypic member, 1,8-diaminooctane (VL-004), exceeds Spd in its ability to induce mitophagy and protect against oxidative stress. VL-004 activity is mediated by canonical aging genes and promotes lifespan and healthspan in C. elegans. Moreover, it enhances mitophagy and protects against oxidative injury in rodent and human cells. Initial structural characterization suggests simple rules for the design of compounds with improved bioactivity, opening the way for a new generation of agents with a potential to promote healthy aging.
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