Researchers in California believe they have developed a new technique that can potentially slow or reverse the aging process.

A team of researchers from Caltech and UCLA developed a new approach to removing cellular damage that accumulates with age by removing mutated DNA from mitochondria, the small organelles that produce most of the chemical energy within a cell.

There are hundreds to thousands of mitochondria per cell, each of which carries its own small circular DNA genome—mtDNA—the products of which are required for energy production. However, mtDNA has limited repair abilities, which means normal and mutant versions of mtDNA are often found in the same cell, a condition known as heteroplasmy.

While most people start off life with some level of heteroplasmy, the levels of mutant mtDNA increase throughout life and when a critical threshold of mutant mtDNA is passed, cells become nonfunctional or die.

The accumulation of mutant mtDNA over a lifetime is believed to be a contributor to aging and degenerative diseases of aging including Alzheimer’s, Parkinson’s and sarcopenia—age-related muscle loss and frailty. Other inherited defects in mtDNA are linked to a number of conditions found in children including autism.

“We know that increased rates of mtDNA mutation cause premature aging,” Bruce Hay, Caltech professor of biology and biological engineering, said in a statement. “This, coupled with the fact that mutant mtDNA accumulates in key tissues such as neurons and muscle that lose function as we age, suggests that if we could reduce the amount of mutant mtDNA, we could slow or reverse important aspects of aging.”

The team—in collaboration with Ming Guo, the P. Gene and Elaine Smith Chair in Alzheimer’s Disease Research and professor of neurology and pharmacology at UCLA and UCLA graduate student Ting Zhang—genetically engineered the common fruit fly—Drosophila—so that about 75 percent of the mtDNA in muscles required for flight, one of the most energy demanding tissues in the animal kingdom, underwent mutation in early adulthood.

Mutations in mtDNA are often not repaired, unlike mutations in the DNA in the nucleus, which can be corrected through cellular repair mechanisms.

However, through a process called mitophagy, cells can break down and remove dysfunctional mitochondria.

In the study, the research team found that when they artificially increased the activity of the genes that promote mitophagy, including that of several genes implicated in familial forms of Parkinson’s disease, the fraction of mutated mtDNA in the fly muscle cells was dramatically reduced.

In the experiment, overexpressing the gene parkin—which is known to specifically promote the removal of dysfunctional mitochondria and is mutated in familial forms of Parkinson’s disease—reduced the fraction of mutant mtDNA from 76 percent to 5 percent, while the overexpression of the gene Atg1 reduced the fraction to 4 percent.

“Such a decrease would completely eliminate any metabolic defects in these cells, essentially restoring them to a more youthful, energy-producing state,” Hay said. “The experiments serve as a clear demonstration that the level of mutant mtDNA can be reduced in cells by gently tweaking normal cellular processes.

“Now that we know mtDNA quality control exists and can be enhanced, our goal is to work with Dr. Guo’s lab to search for drugs that can achieve the same effects,” he added. “Our goal is to create a future in which we can periodically undergo a cellular housecleaning to remove damaged mtDNA from the brain, muscle, and other tissues. This will help us maintain our intellectual abilities, mobility, and support healthy aging more generally.”

The study, which was published in Nature Communications on Nov. 14, can be viewed here.