Fountain of youth unfolded

NORTHWESTERN (US)—Damaged or misfolded proteins, common in many aging-related diseases, can be detected much sooner than previously thought. With early intervention, damage might be delayed, a new study finds.

Researchers at Northwestern University studied seven different proteins of the worm C.elegans and discovered that each protein misfolds during adulthood—long before any behavioral or physiological change is evident.

Genes that regulate lifespan were first discovered in C. elegans, a transparent roundworm that is a favorite organism of biologists because its biochemical environment and fundamental mechanisms are similar to that of human beings—and because its genome, or complete genetic sequence, is known.

The misfolding coincided with the loss of a critical protective cellular mechanism: the ability to activate the heat shock response, an ancient genetic switch that senses damaged proteins and protects cells by preventing protein misfolding.

“I didn’t expect the results to be so dramatic, for these different proteins that vary in concentration and are expressed in diverse tissues to collapse at the same time,” says lead researcher Richard Morimoto. “This suggests the animal’s protective cellular stress response becomes deficient during aging.”

The researchers wondered if the misfolding could be prevented or delayed to minimize the damage.  To find out, they gave the animals the equivalent of a vitamin, boosting the heat shock response early in the animal’s development, prior to protein damage. Now, instead of misfolding around day four, the equivalent of early adulthood in the worm, the proteins didn’t start misfolding until day 12. (Behavioral changes didn’t appear for at least three days after misfolding. The average lifespan of the worm is 21 days.)

“Our data suggest that, in terms of therapeutics, you have to start early to prevent damage and keep cells healthy,” explains Morimoto, Bill and Gayle Cook Professor of Biochemistry, Molecular Biology, and Cell Biology in Northwestern’s Weinberg College of Arts and Sciences. “When you see a loss of function, it’s too late.”

The results of the study, which was supported by the National Institute of General Medical Sciences and the National Institute on Aging, were published online Aug. 24 by the Proceedings of the National Academy of Sciences.

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