Mitochondrial dysfunction plays a central role in aging, but the exact biological causes have yet to be determined. In aging research, scientists at the University of Washington School of Medicine reported an experimental approach that slowed the rate of physical decline and extended the lifespan of roundworms commonly used in biological studies, C. elegans.
Roundworms, which have an average lifespan of only two to three weeks, are commonly used in aging studies. As a result, it is usually possible to receive study results quickly. Scientists in this study were keen to determine the role of mitochondrial dysfunction in roundworm aging and whether some of this decline could be halted or reversed.
Numerous essential functions of these cellular organelles, such as energy molecule synthesis, immunological signaling and genetic regulation, are controlled by the mitochondrial membrane potential.
Scientists noted, “Decreased mitochondrial membrane potential is an attractive explanation for the complex dysfunctions of aging. However, it is unclear whether the reduction of mitochondrial voltage potential is a cause or a consequence of cellular aging.”
The study used a method known as optogenetics, which precisely controls a cell’s biological process through light to achieve the elusive goal of verifying causality. Using a light-activated proton pump, they were able to specifically increase the mitochondrial membrane potential in the cells of adult roundworms. This device was known as “mitochondria-ON”.
The transparent bodies of roundworms and the ability of all their cells to see under a microscope make this method particularly effective.
The juvenile worm populations developed for this study were maintained in complete darkness from conception to the first day of adulthood. They were then subjected to the test conditions.
The scientists’ three different types of roundworms experienced different age-related indicators of aging that were reversed by the optogenetics method, which also reproducibly extended the lifespan of the treated worms compared to untreated worms.
Scientists noted, “In the roundworms, we were able to show experimentally that harnessing the energy of light to enlarge the mitochondrial membrane during adulthood is sufficient to slow down aging.”
“Roundworms, like humans, have more difficulty moving as they age. Despite aging, mitochondria-ON activation improved the threshing rate of worms placed in liquid.”
“Those results seem to suggest that age-related physiological decline in the roundworms could be ameliorated by directly reversing the loss of mitochondrial voltage potential that occurs with the passage of time.”
- Berry, BJ, Vodičková, A., Müller-Eigner, A. et al. Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan. Natural Aging (2022). DOI: 10.1038/s43587-022-00340-7