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Researcher studies worms to reveal the fountain of youth

by Thea Singer

In 2010, when Pres­i­dent Barack Obama spoke at North­eastern in sup­port of Martha Coakely’s guber­na­to­rial bid, he looked markedly dif­ferent from the can­di­date we’d seen on the cam­paign trail just two years ear­lier: His black hair was salted with white, his face thinner, his wrin­kles more deeply etched.

Assis­tant pro­fessor Javier Apfeld, who joined the Col­lege of Sci­ence this fall, wants to under­stand that aging process. With worms as his sub­jects, he plumbs the cel­lular mech­a­nisms dri­ving the com­plex pro­tein inter­ac­tions reg­u­lating lifespan, some of which—remarkably—have been con­served through evo­lu­tion all the way from his micro­scopicCaenorhab­ditis ele­gans to us.

What con­trols how long an organism lives?” he asks. “I study that ques­tion in worms, which are a great model because they live only about two weeks, so I can do exper­i­ments quickly and rel­a­tively inex­pen­sively. Of course, worms are worms—they’re not mice, they’re not humans. But many of the genes that affect lifespan in worms affect lifespan in other organ­isms. Worms are, in many ways, leading the way in under­standing aging.”

In his lab at North­eastern, Apfeld manip­u­lates the worms’ genes and envi­ron­ment in an attempt to learn what fac­tors lengthen or shorten their lives—and even whether there’s a limit to how long they can live. The answers could pro­vide clues to increasing our own longevity.

A market for electrons

Apfeld didn’t so much choose the aging field as the field chose him. As a grad­uate stu­dent at the Uni­ver­sity of Cal­i­fornia, San Fran­cisco, he heard mol­e­c­ular biol­o­gist Cyn­thia Kenyon describe how worms with a muta­tion in a par­tic­ular gene had double the lifespan of those without it. “It was unbe­liev­able.” he says. “My head was exploding.”

That enthu­siasm extends to his cur­rent research: How “oxi­da­tion” and “reduction”—the trading of elec­trons between pro­tein molecules—relates to aging. He thinks of the exchange, dubbed “redox,” as a “market for elec­trons in the cell.”

Were that market to expe­ri­ence free fall, mayhem could ensue: Research has linked increased pro­tein oxi­da­tion to age-​​related dis­eases such as cancer, heart dis­ease, dia­betes, and Alzheimer’s and Parkinson’s diseases.

We are trying to under­stand the causes of aging by linking the mech­a­nisms that con­trol the oxi­da­tion of pro­teins at the cel­lular level with the mech­a­nisms that deter­mine the lifespan of the whole organism,” Apfeld says.

Dig­ging deeper

It’s a daunting task. A break­through study that Apfeld co-​​authored while an instructor at Har­vard Med­ical School pro­vided one piece of the puzzle, thanks to a new flu­o­res­cent sensor tech­nology that pre­cisely mea­sures oxi­da­tion reac­tions in the cells of live organisms.

The team dis­cov­ered that a com­pound called glutathione—found in animal and plant tis­sues, including those of worms and humans—plays a very dif­ferent role in redox than orig­i­nally thought. Rather than acting as a buffer against oxi­da­tion, it may amplify or temper mes­sages con­trol­ling the process.

Glu­tathione, it turns out, func­tions as a kind of mol­e­c­ular micro­phone.
The finding could change the course of research into the role of oxi­da­tion in age-​​related dis­eases. It could also have impor­tant impli­ca­tions for treat­ments, including the use of antiox­i­dant supplements.

At North­eastern, Apfeld will dig deeper into causes: He is inves­ti­gating what drives the glu­tathione com­mu­ni­ca­tion system and how oxi­da­tion changes the func­tion of the affected pro­teins. “When you work with smart and curious grad­uate and under­grad­uate stu­dents like those here,” he says, “lots of cool things can happen.”

Originally published in news@Northeastern on March 22, 2016.

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