Translational Medicine, School of Science, Engineering and Environment (SEE), University of Salford, Greater Manchester M5 4BR, UK.
Aging (Albany NY). 2023 Nov 9;15(21):11764-11781. doi: 10.18632/aging.205229.
Aging is a continuous degenerative process caused by a progressive decline of cell and tissue functions in an organism. It is induced by the accumulation of damage that affects normal cellular processes, ultimately leading to cell death. It has been speculated for many years that mitochondria play a key role in the aging process. In the aim of characterizing the implications of mitochondria in aging, here we used () as an organismal model treated a panel of mitochondrial inhibitors and assessed for survival. In our study, we assessed survival by evaluating worm lifespan, and we assessed aging markers by evaluating the pharyngeal muscle contraction, the accumulation of lipofuscin pigment and ATP levels. Our results show that treatment of worms with either doxycycline, azithromycin (inhibitors of the small and the large mitochondrial ribosomes, respectively), or a combination of both, significantly extended median lifespan of , enhanced their pharyngeal pumping rate, reduced their lipofuscin content and their energy consumption (ATP levels), as compared to control untreated worms, suggesting an aging-abrogating effect for these drugs. Similarly, DPI, an inhibitor of mitochondrial complex I and II, was capable of prolonging the median lifespan of treated worms. On the other hand, subjecting worms to vitamin C, a pro-oxidant, failed to extend lifespan and upregulated its energy consumption, revealing an increase in ATP level. Therefore, our longevity study reveals that mitochondrial inhibitors (i.e., mitochondria-targeting antibiotics) could abrogate aging and extend lifespan in .
衰老是由生物体中细胞和组织功能的逐渐衰退引起的连续退化过程。它是由影响正常细胞过程的损伤积累引起的，最终导致细胞死亡。多年来，人们一直推测线粒体在衰老过程中起着关键作用。为了研究线粒体在衰老过程中的作用，我们在此使用 () 作为生物体模型，用一组线粒体抑制剂处理，并评估其存活率。在我们的研究中，我们通过评估线虫的寿命来评估存活情况，通过评估咽肌收缩、脂褐素积累和 ATP 水平来评估衰老标志物。我们的结果表明，用强力霉素（小线粒体核糖体抑制剂）、阿奇霉素（大线粒体核糖体抑制剂）或两者的组合处理线虫，可显著延长线虫的中位寿命，增强其咽泵速率，减少其脂褐素含量和能量消耗（ATP 水平），与未处理的对照线虫相比，表明这些药物具有抗衰老作用。同样，线粒体复合物 I 和 II 的抑制剂 DPI 能够延长处理后的线虫的中位寿命。另一方面，用维生素 C（一种促氧化剂）处理线虫未能延长其寿命，反而增加了其能量消耗，揭示了 ATP 水平的增加。因此，我们的长寿研究表明，线粒体抑制剂（即靶向线粒体的抗生素）可以延缓衰老并延长线虫的寿命。
