Photo credit: Anil Rana/Nature Communications

A team of UCLA scientists believe that their developed technique could eventually help delay the onset of Parkinson’s disease, Alzheimer’s disease, cancer, stroke, cardiovascular disease and other age-related diseases in humans.

The technique has been created from working with middle-aged fruit flies, which they have claim to have improved an insect’s health while slowing down their ageing process. The researchers zeroed in on mitochondria, which can often become damaged with age. When cells can’t eliminate the damaged mitochondria, they can become toxic and contribute to a wide range of age-related diseases, said David Walker, ph.D, a UCLA professor of integrative biology and physiology, and the study’s senior author.

The research found that as the fruit flies reach middle age, about one month into their two-month lifespan, their mitochondria changes 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,” he said. “And our research suggests dysfunctional mitochondria accumulate with age, rather than being discarded.”

The study, published in Nature Communications, reports that the UCLA scientists removed the damaged mitochondria bu breaking up enlarged mitochondria into smaller pieces. As a result of this, 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 the protein Drp1 in ageing, at least in flies and mice, where levels of Drp1 drop with age.

“We find that short-term induction of Drp1, in midlife, is sufficient to improve organismal health and prolong lifespan, and observe a midlife shift toward a more elongated mitochondrial morphology, which is linked to the accumulation of dysfunctional mitochondria in aged flight muscle. Promoting Drp1-mediated mitochondrial fission, in midlife, facilitates mitophagy and improves both mitochondrial respiratory function and proteostasis in aged flies,” write the investigators.

“Finally, we show that autophagy is required for the anti-aging effects of midlife Drp1-mediated mitochondrial fission. Our findings indicate that interventions that promote mitochondrial fission could delay the onset of pathology and mortality in mammals when applied in midlife.”

To break apart the flies’ mitochondria, Anil Rana, Ph.D., 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 more or less the same time, Dr. 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 antiaging effects, whereas 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 Dr. 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.”

Dr Walker expressed hope that a similar technique could eventually help humans by slowing ageing and delaying ageing-related diseases. He said the fact that the new approach was effective, even after a short time, is significant due to the long term use of nearly any drug which can have harmful side effects in humans.

In addition, one of the long term goals from this study is to eventually develop pharmaceuticals that would mimic the effects of Drp1, in order to extend people’s lives and lengthen “healthspans”, meaning the number of healthy years in their lives.