As people age, their mitochondria—the organelles that produce energy in cells—tend to become damaged and accumulate in muscles and organs. While there, they can become toxic and eventually cause age-related diseases. Now UCLA researchers are zeroing in on these energy centers, boosting a protein in middle-aged fruit flies that helps them clear damaged mitochondria from their cells.
Using this approach, the UCLA team extended the lifespans of the flies, according to a press release. They hope to translate the research into humans to delay aging and stave off age-related diseases.
The new research shows that as fruit flies reach middle age, their mitochondria change shape. Instead of staying small and round, they grow longer and larger, and the cells can’t eliminate them.
"We think the fact that the mitochondria become larger and elongated impairs the cell's ability to clear the damaged mitochondria," said senior author David Walker, a UCLA professor of integrative biology and physiology, in the release. "And our research suggests dysfunctional mitochondria accumulate with age, rather than being discarded."
To break the enlarged mitochondria into smaller, more easily cleared pieces, the UCLA team upregulated the protein Drp1 for one week in middle-aged fruit flies. The flies were able to eliminate these smaller, damaged mitochondria without affecting healthy mitochondria. By switching off the flies’ Atg1 gene and rendering their cells unable to clear the broken-apart mitochondria, the scientists proved that Atg1 is essential for the removal of these damaged mitochondria.
After having their Drp1 levels boosted, the fruit flies were more active and energetic, and they had better endurance, the team said. On average, female flies lived 20% longer than their typical lifespan of two months, while male flies lived 12% longer. The findings are published in Nature Communications.
"It's like we took middle-aged muscle tissue and rejuvenated it to youthful muscle," said Walker, a member of UCLA's Molecular Biology Institute. "We actually delayed age-related health decline. And seven days of intervention was sufficient to prolong their lives and enhance their health."
Specifically, the Drp1 treatment warded off the onset of leaky intestines, which tends to afflict fruit flies about a week before they die. Walker hopes that a similar technique could postpone the onset of age-related disorders in humans, including Alzheimer’s and Parkinson’s disease, stroke, cancer and cardiovascular disease.
While mitochondria have been known to play a role in aging, Newcastle University scientists proved for the first time last year that they actually trigger aging. When they deleted all of the mitochondria from lab-grown human cells, they found that the cells appeared younger. And researchers at the University of Sheffield identified one of the enzymes that repairs mitochondrial DNA, which could be used to deprive cancer cells of their energy source.
Walker’s long-term goal is to create a drug that mimics the effects of Drp1. A Drp1-based approach is attractive because it works quickly and therefore is less likely to cause harmful side effects, he said.