Antibiotics that target mitochondria extend lifespan in C. elegans

Bonuccelli, Gloria; Brooks, Darren R.; Shepherd, Sally; Sotgia, Federica; Lisanti, Michael P.; Brooks, Darren R; Lisanti, Michael P

Abstract

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 .

Citation

Bonuccelli, G., Brooks, D. R., Shepherd, S., Sotgia, F., Lisanti, M. P., Brooks, D. R., & Lisanti, M. P. (in press). Antibiotics that target mitochondria extend lifespan in C. elegans. Aging, 15(21), 11764-11781. https://doi.org/10.18632/aging.205229

• Journal Article Type: Article
• Acceptance Date: Sep 25, 2023
• Online Publication Date: Nov 9, 2023
• Deposit Date: Dec 6, 2023
• Publicly Available Date: Dec 6, 2023
• Journal: Aging
• Publisher: Impact Journals
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 21
• Pages: 11764-11781
• DOI: https://doi.org/10.18632/aging.205229
• Keywords: lifespan, lipofuscin, mitochondria, C. elegans, Anti-Bacterial Agents - pharmacology, Mitochondria - metabolism, Caenorhabditis elegans Proteins - genetics - metabolism, Caenorhabditis elegans - metabolism, Longevity, metabolism, Animals, aging, Lipofuscin - metabolism, DPI, Adenosine Triphosphate - metabolism, antibiotics