Scientists say that a gene, called parkin, can delay the onset of aging and make fruit flies live longer. They believe their findings might have important implications for the aging process and development of disease in human beings.

The study was published in the peer-reviewed journal Proceedings of the National Academy of Sciences (PNAS).

Parkin, a gene which has been previously implicated in Parkinson's disease, has at least two important functions:
  • It marks damaged proteins so that they can be gotten rid of before they become toxic
  • It helps remove damaged mitochondria from cells (scientists believe)
Senior author, David Walker, associate professor of integrative biology and physiology at UCLA, said:

"Aging is a major risk factor for the development and progression of many neurodegenerative diseases. We think that our findings shed light on the molecular mechanisms that connect these processes."

The team demonstrated that with fruit flies parkin was able to modulate the aging process. A fruit fly's normal lifespan is less than two months. They compared a group of flies that received parkin with another group that did not. The ones in the parkin group lived 25% longer.

Walker said:

"In the control group, the flies are all dead by Day 50. In the group with parkin overexpressed, almost half of the population is still alive after 50 days. We have manipulated only one of their roughly 15,000 genes, and yet the consequences for the organism are profound."

Lead author, Anil Rana, a postdoctoral scholar in Walker's laboratory, said "Just by increasing the levels of parkin, they live substantially longer while remaining healthy, active and fertile. That is what we want to achieve in aging research - not only to increase their life span but to increase their health span as well."

The scientists believe that treatment to increase parkin expression could well delay the onset and progression of age-related diseases such as Parkinson's.

"Parkin" does not just sound like the disease "Parkinson's", there is a relationship. Early-onset Parkinson's-like symptoms occur in people who are born with a mutation in the parkin gene. Most patients with Parkinson's disease develop symptoms during old age. In about 10% of Parkinson's cases, the cause is mutations in specific genes, one of them being parkin.

Walker said:

"Our research may be telling us that parkin could be an important therapeutic target for neurodegenerative diseases and perhaps other diseases of aging. Instead of studying the diseases of aging one by one - Parkinson's disease, Alzheimer's disease, cancer, stroke, cardiovascular disease, diabetes - we believe it may be possible to intervene in the aging process and delay the onset of many of these diseases. We are not there yet, and it can, of course, take many years, but that is our goal."

'The garbage men in our cells go on strike'

Proteins must fold properly to function correctly. Folding is a complex procedure. As we become older, damaged or misfolded proteins build up in our cells. When a protein does not fold properly, it can often be repaired by the cellular machinery. When repairs cannot be done, parkin marks the damaged protein, making it easier to identify it and get rid of it before it becomes toxic.

Walter said "If a protein is damaged beyond repair, the cell can recognize that and eliminate the protein before it becomes toxic. Think of it like a cellular garbage disposal. Parkin helps to mark damaged proteins for disposal. It's like parkin places a sticker on the damaged protein that says 'Degrade Me,' and then the cell gets rid of this protein. That process seems to decline with age. As we get older, the garbage men in our cells go on strike. Overexpressed parkin seems to tell them to get back to work."

Rana concentrated on determining what the effects of increased parkin activity are on cells and tissue. The team wanted to know whether fruit flies with higher parkin levels had fewer damaged proteins in old age. "The remarkable finding is yes, indeed," Walker said.

Parkin was also found to mark damaged mitochondria, signaling the cell to get rid of it. Mitochondria are small power generators inside cells, they control cell growth and also tell it when to die. As we age, mitochondria become less efficient and less active. Lower mitochondrial activity has been associated with Parkinson's and Alzheimer's diseases, other neurodegenerative illnesses, and the aging process.

We know parkin is good. What about more parkin, is that even better?

The scientists found that while higher parkin levels can extend the lifespan of fruit flies, excess parkin does them harm:
  • When normal levels of parkin were quadrupled, the flies lived 25% longer
  • When parkin levels were raised by a factor of 30, they died sooner
Rana explained that too much parkin leads to the elimination of healthy proteins within cells.

Walker explained that fruit flies are ideal models for studying human aging because they have the parkin gene and we have their whole genome mapped, allowing scientists to switch individual genes on and off.

Previous studies had shown that fruit flies live less time when parkin is removed. The scientists do not yet know what the ideal quantity of parkin would be for humans.

After increasing parkin activity in every cell in the fruit fly, Rany then carried out an experiment in which parkin expression was only increased in the nervous system; this also made them live longer.

Walker said "This tells us that parkin is neuroprotective during aging," Walker said. "However, the beneficial effects of parkin are greater - twice as large - when we increased its expression everywhere. We were excited about this research from the beginning but did not know then that the life span increase would be this impressive."

Walker added:

"Imagine the damage the accumulation of protein trash is doing to the cell," Walker said. "With increased Parkin, the trash has been collected. Without it, the garbage that should be discarded is accumulating in the cells."

Written by Christian Nordqvist