Mitochondria — the tiny power plants of the cell — simultaneously produce energy and accumulate mutations in their own DNA, which over time disrupt the functioning of the entire body. Researchers from UCLA and Caltech have found a way to selectively remove precisely the damaged copies of this DNA, strengthening the cell's natural cleanup mechanisms.
The accumulation of mutations in mitochondrial DNA is linked to Parkinson's disease, Alzheimer's disease, cardiac pathologies, and a general loss of strength in old age. Inherited defects cause severe childhood diseases. The scientists set themselves the task not of treating each disease separately, but of reducing the proportion of damaged mitochondrial DNA in cells in order to slow down the very process of aging.
At the center of the work is a model based on fruit flies Drosophila, created by the laboratories of Ming Guo of UCLA and Bruce Hay of Caltech. In this model organism, the researchers managed to activate autophagy — the process by which a cell "eats" and recycles its own damaged components. As a result, they were able to remove up to 95 percent of mutant mitochondrial DNA. Activation of pathways associated with protection against Parkinson's disease produced a similar effect.
Importantly, the cleanup process already exists in the cell but does not work efficiently enough. The scientists merely enhanced it, without adding any foreign substances. This distinguishes the approach from attempts to fully replace mitochondria or edit DNA directly. However, all the data were obtained in flies, and transferring the results to humans requires further research.
Imagine a cell as an apartment where old light bulbs gradually dim and flicker. Instead of rewiring the whole place, the owner boosts the work of the cleaner, who finds and throws out only the faulty lamps. That is exactly what activation of autophagy looks like in the experiment: the cell handles the garbage itself if given a little help.
The study was published in Nature Communications in 2016 and was funded by the US National Institutes of Health, the Kenneth Glenn Family Foundation, and the Ellison Medical Foundation. The authors declared no conflicts of interest. Future plans include the search for drugs that mimic this effect and testing in other models.
The work shows that aging can partly be viewed as the gradual accumulation of cellular garbage, which in principle can be controlled by strengthening the cell's own quality-control systems.
