Zhaohui Sunny Zhou

Researcher studies protein’s role in aging

by Angela Herring

With time, the amino acid known as asparagine will even­tu­ally degrade. Long con­sid­ered a type of pro­tein “damage,” the phe­nom­enon has come to be accepted as yet another part of aging: our hair turns gray, our joints begin to ache, and our asparagine turns into isoas­partic acid.

The sur­prising thing about this change is that it forces the protein’s back­bone to follow a new track, just like a rail­road switch sends a train on an entirely dif­ferent journey. “This is excep­tion­ally rare,” said chem­istry and chem­ical biology asso­ciate pro­fessor Sunny Zhou, who recently received a $1 mil­lion grant from the National Insti­tutes of Health to study the eti­o­logic role of isoas­partic acid, or isoAsp, in aging and dis­ease. It’s research that could dra­mat­i­cally change how doc­tors treat dis­eases such as Alzheimer’s, which sig­nif­i­cantly ele­vates patients’ isoAsp levels.

According to Zhou, the rate at which isoAsp forms depends on the sequence of amino acids in the pro­tein. If asparagine sits next to the amino acid pro­line, it will take a long time to degrade. If it’s next to glycine, on the other hand, it may take just half a day. Luckily, there’s an anti­dote. The enzyme “pro­tein isoas­par­tate methyl­trans­ferase,” or PIMT, can rec­tify the damage.

The degra­da­tion process that leads to isoAsp hap­pens in vir­tu­ally all cells and PIMT is present in almost all animal sys­tems except baker’s yeast; how yeast cells reg­u­late isoAsp remains a mys­tery. Addi­tion­ally, animal studies have shown that elim­i­nating PIMT from the body does reduce life expectancy—but not through aging. “IsoAsp levels in these ani­mals increase,” said Zhou. “But only twofold, not ten­fold.” This sug­gests some­thing else must be at play in the reg­u­la­tion process in other ani­mals too, not just yeast.

IsoAsp has the same mol­e­c­ular weight as aspartic acid, making it extremely dif­fi­cult to detect. At least it used to be. In pre­vious research as a fac­ulty fellow at Northeastern’s Bar­nett Insti­tute of Chem­ical and Bio­log­ical Analysis, Zhou helped develop a method for easily tracking it down.

Degra­da­tion cannot be pre­vented, he said, because it hap­pens spon­ta­neously. But if researchers found a way to repair the damage, their work could have a sig­nif­i­cant effect on the ability to treat age-​​related dis­ease such as Alzheimer’s.

“If we can find the machinery that gets rid of isoas­partic faster, then we can somehow use a driver to boost that machinery,” Zhou said, noting that the dam­aged cells in an Alzheimer’s brain con­tain up 70 per­cent isoas­partic acid. “That’s the hope.”

Originally published in news@Northeastern on July 23, 2013

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