UCLA biologists say they have slowed aging and extended the lifespan of middle-aged fruit flies. According to David Walker, a UCLA professor of integrative biology and physiology, and the study's senior author, his team found that as fruit flies reach middle age—about one month into their two-month lifespan—their mitochondria change from their original small, round shape.
"We think the fact that the mitochondria become larger and elongated impairs the cell's ability to clear the damaged mitochondria," Walker reports. "And our research suggests dysfunctional mitochondria accumulate with age, rather than being discarded."
In the study, published today in Nature Communications, UCLA scientists removed the damaged mitochondria by breaking up enlarged mitochondria into smaller pieces—and when they did, the flies became more active and more energetic and had more endurance. Following the treatment, female flies lived 20% longer than their typical lifespan, while males lived 12% longer, on average.
The research highlights the importance of a protein called Drp1 in aging. At least in flies and mice, levels of Drp1 decline with age.
To break apart the flies' mitochondria, Anil Rana, a UCLA project scientist and the study's lead author, increased their levels of Drp1. This enabled the flies to discard the smaller, damaged mitochondria, leaving only healthy mitochondria. Drp1 levels were increased for one week starting when the flies were 30 days old.
At essentially the same time, Rana demonstrated that the flies' Atg1 gene also plays an essential role in turning back the clock on cellular aging. He did this by "turning off" the gene, rendering the flies' cells unable to eliminate the damaged mitochondria. This proved that Atg1 is required to reap the procedure's anti-aging effects: While Drp1 breaks up enlarged mitochondria, the Atg1 gene is needed to dispose of the damaged ones.
"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."
Caption: Fruit flies' mitochondria (in green) at 10 days (top left), 28 days (top right) and 37 days old (both bottom images). At bottom right, the mitochondria have returned to a more youthful state after UCLA biologists increased the fly's level of a protein called Drp1. Image courtesy of Nature Communications/Anil Rana.