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Scientists boost cellular “trash collection” to gives flies extra life

May 7, 2013
Courtesy of UCLA
and World Science staff

Sci­en­tists say they have iden­ti­fied a gene that can make flies stay alive, and in good health, long­er—and the find­ings could help hu­mans.

Bi­ol­o­gists say the gene, called par­kin, serves at least two roles: it marks dam­aged pro­teins so cells can dis­card them be­fore they be­come tox­ic, and helps re­move dam­aged com­part­ments called mi­to­chon­dria from cells. 

The study is­n’t the first time sci­en­tists have linked the ag­ing pro­cess to cel­lu­lar “trash col­lec­tion” pro­cesses, and their grad­u­al de­cline, a field of re­search that’s at­tract­ing grow­ing in­ter­est.

In the new stu­dy, pub­lished May 6 in the early on­line edi­tion of the jour­nal Pro­ceed­ings of the Na­t­ional Acad­e­my of Sci­ences, Da­vid Walk­er of the Uni­vers­ity of Cal­i­for­nia Los An­ge­les and col­leagues found that boost­ing par­kin lev­els in the cells of fruit flies could ex­tend their lives by more than 25 per­cent. 

Boost­ing it too much, on the oth­er hand, short­ened the in­sects’ lives—as if they had be­come sad­dled with too many zeal­ous cel­lu­lar trash col­lec­tors, per­haps toss­ing out good pro­teins along with the bad. 

So a way to apply the find­ings to hu­mans might be to find a way to boost the ac­ti­vity of par­kin, which we al­so have, by some as-yet-unknown op­ti­mal amount, the sci­en­tists said.

“Par­kin could be an im­por­tant ther­a­peu­tic tar­get for neu­rode­gen­er­a­tive dis­eases and per­haps oth­er dis­eases of ag­ing,” Walk­er said. The ma­ni­pu­lated flies “live sub­stanti­ally long­er while re­main­ing healthy, ac­tive and fer­tile,” com­pared to their nor­mal life­span of less than two months, added An­il Rana, a post­doc­tor­al schol­ar in Walk­er’s lab­o­r­a­to­ry and lead au­thor of the re­search.

Treat­ments to in­crease par­kin ac­ti­vity may de­lay Par­kin­son’s dis­ease and oth­er age-re­lat­ed dis­eases, the bi­ol­o­gists be­lieve. If par­kin sounds re­lat­ed to Par­kin­son’s, it is. While most Par­kin­son’s pa­tients get the dis­ease in old­er age, some who are born with a muta­t­ion in the par­kin gene de­vel­op early Par­kin­son’s-like symp­toms.

To func­tion prop­er­ly, pro­teins—mo­le­cules that our bod­ies make and use for an ar­ray of func­tions—must fold cor­rect­ly, and they fold in com­plex ways. As we age, our cells ac­cu­mu­late dam­aged or mis­folded pro­teins. When pro­teins fold incor­rect­ly, the cel­lu­lar ma­chin­ery can some­times re­pair them. If not, par­kin en­ables cells to dis­card the dam­aged pro­teins, said Walk­er.

“If a pro­tein is dam­aged be­yond re­pair, the cell can rec­og­nize that and elim­i­nate the pro­tein be­fore it be­comes tox­ic,” he said. “Par­kin helps to mark dam­aged pro­teins for dis­pos­al. It’s like par­kin places a stick­er on the dam­aged pro­tein that said ‘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 [over­active] par­kin seems to tell them to get back to work.”

Rana fo­cused on the ef­fects of in­creased par­kin ac­ti­vity at the cel­lu­lar and tis­sue lev­els. Do flies with more par­kin show few­er dam­aged pro­teins at an ad­vanced age? “The re­mark­a­ble find­ing is yes, in­deed,” Walk­er said.

Par­kin has re­cently been found to per­form a si­m­i­lar func­tion with re­gard to mi­to­chon­dria, ti­ny power-generating com­part­ments in cells that con­trol cell growth and tell cells when to live and die. Mi­to­chon­dria be­come less ef­fi­cient and ac­tive as we age, a de­cline im­pli­cat­ed in Alzheimer’s, Par­kin­son’s, oth­er neu­rode­gen­er­a­tive dis­eases and ag­ing gen­er­al­ly, Walk­er said.

While the re­search­ers found that in­creased par­kin can ex­tend the life of fruit flies, Rana al­so dis­cov­ered that too much par­kin can have the op­po­site ef­fect — it be­comes tox­ic. When he quadru­pled the nor­mal amount of par­kin, the fruit flies lived sub­stanti­ally long­er, but when he in­creased the amount 30-found, the flies died soon­er.

“If you bom­bard the cell with too much par­kin, it could start elim­i­nat­ing healthy pro­teins,” Rana said. Pre­vi­ous re­search has shown that fruit flies al­so die soon­er when you re­move par­kin, Walk­er not­ed. The re­search­ers al­so found that a good deal of par­kin’s role is in the nerv­ous sys­tem; in­creas­ing its ac­ti­vity in that sys­tem alone seems to ac­count for about half the life-ex­tending ef­fect.

“We were ex­cit­ed about this re­search from the be­gin­ning but did not know then that the life span in­crease would be this im­pres­sive,” Rana said.


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Scientists say they have identified a gene that can make flies stay alive, and in good health, longer—and the findings could help humans. Biologists say the gene, called parkin, serves at least two roles: it marks damaged proteins so cells can discard them before they become toxic, and helps remove damaged compartments called mitochondria from cells. The study isn’t the first time scientists have linked the aging process to such cellular “trash collection” processes, and to their gradual decline, a field of research that’s attracting growing interest. In the new study, published May 6 in the early online edition of the journal Proceedings of the National Academy of Sciences, David Walker of the University of California Los Angeles and colleagues found that boosting parkin levels in the cells of fruit flies could extend their lives by more than 25 percent. Boosting it too much, on the other hand, shortened the insects’ lives—as if they had become saddled with too many zealous cellular trash collectors, perhaps tossing out good proteins along with the bad. So a way to apply the findings to humans might be to find a way to boost the activity of parkin, which we also have, by some as-yet-unknown optimal amount, the scientists said. “Parkin could be an important therapeutic target for neurodegenerative diseases and perhaps other diseases of aging,” Walker said. The manipulated flies “live substantially longer while remaining healthy, active and fertile,” compared to their normal lifespan of less than two months, added Anil Rana, a postdoctoral scholar in Walker’s laboratory and lead author of the research. Treatments to increase parkin activity may delay Parkinson’s disease and other age-related diseases, the biologists believe. If parkin sounds related to Parkinson’s, it is. While most Parkinson’s patients get the disease in older age, some who are born with a mutation in the parkin gene develop early Parkinson’s-like symptoms. To function properly, proteins—molecules that our bodies make and use for an array of functions—must fold correctly, and they fold in complex ways. As we age, our cells accumulate damaged or misfolded proteins. When proteins fold incorrectly, the cellular machinery can sometimes repair them. If not, parkin enables cells to discard the damaged proteins, said Walker. “If a protein is damaged beyond repair, the cell can recognize that and eliminate the protein before it becomes toxic,” he said. “Parkin helps to mark damaged proteins for disposal. It’s like parkin places a sticker on the damaged protein that said ‘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 focused on the effects of increased parkin activity at the cellular and tissue levels. Do flies with more parkin show fewer damaged proteins at an advanced age? “The remarkable finding is yes, indeed,” Walker said. Parkin has recently been found to perform a similar function with regard to mitochondria, tiny power-generating compartments in cells that control cell growth and tell cells when to live and die. Mitochondria become less efficient and active as we age, a decline implicated in Alzheimer’s, Parkinson’s, other neurodegenerative diseases and aging generally, Walker said. If parkin is good, is more parkin even better? While the researchers found that increased parkin can extend the life of fruit flies, Rana also discovered that too much parkin can have the opposite effect — it becomes toxic. When he quadrupled the normal amount of parkin, the fruit flies lived substantially longer, but when he increased the amount by a factor of 30, the flies died sooner. “If you bombard the cell with too much parkin, it could start eliminating healthy proteins,” Rana said. Previous research has shown that fruit flies also die sooner when you remove parkin, Walker noted. The researchers also found that a good deal of parkin’s role is in the nervous system; increasing its activity in that system alone seems to account for half of the life-extending effect. “We were excited about this research from the beginning but did not know then that the life span increase would be this impressive,” Rana said.