Mild Mitochondrial Inhibition Slows Aging in Nematode Worms

Researchers here demonstrate that means of mildly inhibiting the production of some of the protein machinery used to generate chemical energy store molecules, adenosine triphosphate, in mitochondria can extend life by 50-70% in nematode worms - a species in which much larger life extension is possible, so this might be viewed as a moderate effect size. Many different approaches to adjusting mitochondrial function can slow aging and extend life in short-lived species. In some cases this works by provoking mitochondria into an alternative pathway for ATP generation that produces a little more oxidative stress than usual, triggering greater cell maintenance activities. The details and dosing matter, however, and there is a fine line between lesser disruption that slows aging versus greater disruption that causes cell and tissue dysfunction to accelerate aging.

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 Caenorhabditis elegans (C. elegans) 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 C. elegans, 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, diphenyleneiodonium chloride (DPI), an inhibitor of mitochondrial complex I and complex 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 C. elegans 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 C. elegans.


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